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## Protocol Section ### Identification Module **NCT ID:** NCT06430242 **Brief Title:** Tele-rehabilitation in Knee Osteo Arthritis **Official Title:** Role of Tele-rehabilitation in Elderly Women With Locomotor Disabilities Due to Knee Osteo Arthritis #### Organization Study ID Info **ID:** RHPT-01 #### Organization **Class:** OTHER **Full Name:** Prince Sattam Bin Abdulaziz University ### Status Module #### Completion Date **Date:** 2024-04-20 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-23 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2024-04-20 **Type:** ACTUAL #### Start Date **Date:** 2023-10-01 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-04-28 **Study First Submit QC Date:** 2024-05-23 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Prince Sattam Bin Abdulaziz University #### Responsible Party **Investigator Affiliation:** Prince Sattam Bin Abdulaziz University **Investigator Full Name:** Gopal Nambi **Investigator Title:** Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Osteoarthritis (OA) is the most common degenerative joint disease with an inflammatory component that starts from the matrix of the articular cartilage. Females are affected more than males and they have marked locomotor disabilities. Moreover, OA patients suffer from a range of extra-articular symptoms which also leads to functional impairment and disability such as fatigue, depression, anxiety, fear of movement, physical inactivity, and decreased muscle strength. OA management with physical therapy and exercise is recognized as the cornerstone of conservative and self-treatment for this chronic disease. The concept of telerehabilitation has been introduced in the field of physical medicine and rehabilitation, which combines telemedicine and rehabilitation interventions to support ongoing rehabilitation services for patients. **Detailed Description:** Osteoarthritis (OA) is the most common degenerative joint disease with an inflammatory component that starts from the matrix of the articular cartilage, progresses with disruption of chondrocyte responses and results in tissue destruction. In OA, primary involvement is seen in the articular cartilage, and progressive damage occurs. Females are affected more than males and they have marked locomotor disabilities. Moreover, OA patients suffer from a range of extra-articular symptoms which also leads to functional impairment and disability such as fatigue, depression, anxiety, fear of movement, physical inactivity, and decreased muscle strength. OA management with physical therapy and exercise is recognized as the cornerstone of conservative and self-treatment for this chronic disease. The lack of professional supervision and feedback will result in reduced participation in continuing OA medical or rehabilitative services, which in turn will reduce the effectiveness of OA treatments. With the development of telemedicine, it has been determined that patients living in remote areas have the chance to communicate with professional physicians simultaneously. The concept of telerehabilitation has been introduced in the field of physical medicine and rehabilitation, which combines telemedicine and rehabilitation interventions to support ongoing rehabilitation services for patients. Internet- based rehabilitation is one of the effective strategies in telerehabilitation. The use of the internet to provide health-related interventions has the potential to reduce the cost of treatment and improve user satisfaction. ### Conditions Module **Conditions:** - Knee Osteoarthritis **Keywords:** - Knee - Osteoarthritis - Locomotor - Disability - Female ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 56 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** In the active group, one of the co-investigators will install and demonstrate the use of the mobile app (Rehab App) on participants' mobile phone and explain the use of the software. The participants will be followed up for the duration of their enrolment in the e-health and tele-rehabilitation service, which can last up to 2 months and the treatment will be monitored. **Intervention Names:** - Device: Tele rehabilitation **Label:** Group A **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Participants in the control group will get the usual treatment from the clinical staff and in-person education, and they will be supervised by one of the assigned research team members every week. **Intervention Names:** - Other: Exercise **Label:** Group B **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Group A **Description:** In the active group, one of the co-investigators will install and demonstrate the use of the mobile app (Rehab App) on participants' mobile phone and explain the use of the software. The participants will be followed up for the duration of their enrolment in the e-health and tele-rehabilitation service, which can last up to 2 months. **Name:** Tele rehabilitation **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - Group B **Description:** Participants in the control group will get the usual treatment from the clinical staff and in-person education, and they will be supervised by one of the assigned research team members every week. **Name:** Exercise **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Which was measured by 10 cm visual analogue scale **Measure:** Pain intensity **Time Frame:** Baseline **Description:** Which was measured by 10 cm visual analogue scale **Measure:** Pain intensity **Time Frame:** 2 months **Description:** Which was measured by 10 cm visual analogue scale **Measure:** Pain intensity **Time Frame:** After 6 months #### Secondary Outcomes **Description:** Which was measured by WOMAC questionnaire **Measure:** Functional disability **Time Frame:** Baseline **Description:** Which was measured by WOMAC questionnaire **Measure:** Functional disability **Time Frame:** 2 months **Description:** Which was measured by WOMAC questionnaire **Measure:** Functional disability **Time Frame:** 6 months **Description:** Which was measured in meters/ second **Measure:** Gait velocity **Time Frame:** Baseline **Description:** Which was measured in meters/ second **Measure:** Gait velocity **Time Frame:** 2 months **Description:** Which was measured in meters/ second **Measure:** Gait velocity **Time Frame:** 6 months **Description:** Which was measured in meters **Measure:** Step length **Time Frame:** Baseline **Description:** Which was measured in meters **Measure:** Step length **Time Frame:** 2 months **Description:** Which was measured in meters **Measure:** Step length **Time Frame:** 6 months **Description:** Which was measured in number of steps per minute **Measure:** Cadence **Time Frame:** Baseline **Description:** Which was measured in number of steps per minute **Measure:** Cadence **Time Frame:** 2 months **Description:** Which was measured in number of steps per minute **Measure:** Cadence **Time Frame:** 6 months **Description:** Which was measured with KOOS questionnaire **Measure:** Quality **Time Frame:** Baseline **Description:** Which was measured with KOOS questionnaire **Measure:** Quality **Time Frame:** 2 months **Description:** Which was measured with KOOS questionnaire **Measure:** Quality **Time Frame:** 6 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients diagnosed with mild to moderate OA by their physicians. * Female in the age range of 45 - 65 years. * Volunteer to participate in the study. * Living independently. * Being able to walk without using an assistive device. * Owning a mobile phone, tablet, or computer with an internet connection. * Being able to use the device without assistance. Exclusion Criteria: * Having been diagnosed with any other systemic rheumatic diseases. * Having been involved in a physiotherapy and rehabilitation program in any health institution in the last 6 months, * Having knee-related surgery, * Having meniscal or ligament-associated tears occurred in the past 6 months, * Having a history of falling more than 2 times in the last 6 months, * Having a history of knee injection in the last 4 weeks or scheduled in the next 8 week, * Being illiterate, having cognitive problems, having blurred vision problem, and having hearing loss. **Gender Based:** True **Gender Description:** Female participants in the age range of 45 - 65 years. **Maximum Age:** 65 Years **Minimum Age:** 45 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Al Kharj **Country:** Saudi Arabia **Facility:** Gopal Nambi **State:** Riyadh **Zip:** 11942 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001168 - Term: Arthritis - ID: D000007592 - Term: Joint Diseases - ID: D000009140 - Term: Musculoskeletal Diseases - ID: D000012216 - Term: Rheumatic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases ### Condition Browse Module - Browse Leaves - ID: M22168 - Name: Osteoarthritis, Knee - Relevance: HIGH - As Found: Knee Osteo Arthritis - ID: M12926 - Name: Osteoarthritis - Relevance: HIGH - As Found: Osteo Arthritis - ID: M4476 - Name: Arthritis - Relevance: LOW - As Found: Unknown - ID: M10621 - Name: Joint Diseases - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: M15045 - Name: Rheumatic Diseases - Relevance: LOW - As Found: Unknown - ID: M6323 - Name: Collagen Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000010003 - Term: Osteoarthritis - ID: D000020370 - Term: Osteoarthritis, Knee ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06430229 **Brief Title:** Atelectasis Frequency in Different Ventilation Modes **Official Title:** Evaluation of Atelectasis Frequency in Different Ventilation Modes Used in General Anesthesia in Children With Lung Ultrasonography #### Organization Study ID Info **ID:** AEŞH-BADEK-2024-152 #### Organization **Class:** OTHER_GOV **Full Name:** Ankara Etlik City Hospital ### Status Module #### Completion Date **Date:** 2024-09-20 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-21 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-09-10 **Type:** ESTIMATED #### Start Date **Date:** 2024-03-20 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-09 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER_GOV **Name:** Ankara Etlik City Hospital #### Responsible Party **Investigator Affiliation:** Ankara Etlik City Hospital **Investigator Full Name:** Ahmet Aras **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** General anesthesia is characterized by temporary loss of consciousness and decreased reflex activity without any change in vital functions. It can be performed with intravenous and/or inhalation agents. During general anesthesia, breathing is stopped and respiratory support is provided to patients with various respiratory equipment and ventilation modes on the anesthesia device. The most commonly used ventilation modes during anesthesia are volume controlled (VCV) and pressure controlled (PCV). In pressure-controlled ventilation, ventilation is provided with the airway pressure determined by the anesthesiologist throughout inspiration. While the pressure is constant during inspiration, the tidal volume is variable. In volume controlled ventilation, ventilation executed at the volume is set by the anesthesiologist. In other words, the determined volume is constant, but airway pressures vary. In pediatric anesthesia practice modes have not been shown to have a clear advantage over each other. Both modes have advantages and disadvantages. With the development of modern anesthesia devices in recent years, safe ventilation can be provided even in very young children with volume controlled mode (VCV). Atelectasis is the restriction of gas exchange due to complete or partial collapse of the lung. Atelectasis can be seen in 90 percent of patients receiving general anesthesia. This incidence is reported to be 68-100 percent in children. Lung ultrasonography is an imaging method with many advantages for imaging lung-related diseases, such as not containing ionizing radiation, being inexpensive, and being performed at the bedside. Recently, its use by anesthesiologists has become widespread in many lung pathologies, including atelectasis. Traditional and modified lung ultrasonography scoring systems can be used to evaluate atelectasis in lung parenchyma with ultrasonography. In addition to the traditional system, modified scoring system also enables to evaluate small subpleural consolidations In this study, it was aimed to compare the effects of volume controlled and pressure controlled ventilation modes used in general anesthesia in children on atelectasis with lung ultrasonography. **Detailed Description:** Traditional and modified lung ultrasonography scoring systems can be used to evaluate atelectasis in the lung parenchyma by ultrasonography. The modified scoring system also provides the opportunity to evaluate small subpleural consolidations in addition to the traditional system. Lung tissue is evaluated between the intercostal spaces. On ultrasound, the pleural line can usually be seen as bright white due to the acoustic impedance difference between the aerated lung tissue and the surrounding tissues. Most of the ultrasound waves are reflected from this line. Due to the constantly reflected ultrasound waves between the pleural line and the transducer, hyperechoic lines parallel to the pleural line, called A lines, can be observed in the parenchyma. Vertical hyperechoic lines emerging from the pleural line in the lung ultrasound image are defined as B lines. B lines follow perpendicular to A lines. B lines accompany the sliding movement of the lungs along with the respiratory movement. The patient is usually evaluated while lying in the supine position. The thorax is divided into 12 quadrants when evaluated with ultrasound for atelectasis. Midsternal line, anterior axillary line, posterior axillary line form the vertical boundaries of the quadrants. Each area is divided into two parts, upper and lower, by a line passing through its midpoint. Left hemithorax anterior upper, lateral upper, posterior upper, anterior lower, lateral lower, posterior lateral; The right hemithorax consists of 12 quadrants: anterior upper, lateral upper, posterior upper, anterior lower, lateral lower, and posterior lateral. The ultrasound probe is advanced transversely and each quadrant is examined. The patient may be asked to turn slightly to the side to evaluate the posterior quadrants. The ultrasound probe is placed vertically on the ribs and the lung parenchyma seen between the intercostal spaces is evaluated. Loss of ventilation is evaluated according to the modified lung ultrasonography scoring system for each quadrant. The score is collected by evaluating 12 quadrants from 0 to 3 and a value between 0-36 is obtained. For each quadrant, 0 represents the region with no ventilation loss and 3 indicates the region with severe ventilation loss. 0 indicates normal tissue with no loss of ventilation and 2 or fewer B lines are observed. 1 indicates little loss of ventilation, 3 or more B lines or one or more subpleural consolidations separated by a normal pleural line are observed. 2 indicates moderate loss of ventilation, observed as multiple fused B lines or multiple small subpleural consolidations separated by thickened or irregular pleural lines. 3 indicates severe loss of ventilation and is observed as consolidation or subpleural consolidation larger than 1x2 cm. Each patient underwent transthoracic lung ultrasonography a total of 4 times: before laryngeal mask airway (LMA), at the 10th minute after LMA, before extubation and at the 10th minute after extubation. In addition, data on respiratory mechanics and hemodynamic parameters were recorded twice, at the 10th minute after LMA and before extubation. ### Conditions Module **Conditions:** - Pulmonary Atelectasis - Mechanical Ventilation Complication - General Anesthesia - Lung Ultrasound **Keywords:** - Pulmonary Atelectasis - Mechanic Ventilation - General anesthesia - Lung Ultrasound ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - OUTCOMES_ASSESSOR **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 110 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients to be ventilated with VCV mode were placed on respiratory support (Dräger Primus) with a breathing rate that would provide 8 ml/kg tidal volume, 5 cmH2O positive end expiratory pressure (PEEP), and 30-35 mmHg end-tidal carbon dioxide concentration (etCO2) level. **Intervention Names:** - Procedure: Volume controlled ventilation (VCV) mode **Label:** Patients ventilated with volume controlled ventilation (VCV) mode **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Appropriate peak inspiratory pressure was set to create a tidal volume of 8 ml/kg in patients who would be ventilated with PCV mode. The number of breaths (Dräger Primus) was adjusted to provide an end-tidal carbon dioxide concentration (etCO2) level of 30-35 mmHg. PEEP was set to 5 cmH2O. **Intervention Names:** - Procedure: Pressure controlled ventilation (PCV) mode **Label:** Patients ventilated with pressure controlled ventilation (PCV) mode **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Patients ventilated with volume controlled ventilation (VCV) mode **Description:** Patients to be ventilated with VCV mode were placed on respiratory support (Dräger Primus) with a breathing rate that would provide 8 ml/kg tidal volume, 5 cmH2O PEEP, and 30-35 mmHg end-tidal carbon dioxide concentration (etCO2) level. Lung ultrasonography was performed at 4 different time periods. Modified lung ultrasonography scores of 12 quadrants were recorded. **Name:** Volume controlled ventilation (VCV) mode **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - Patients ventilated with pressure controlled ventilation (PCV) mode **Description:** Appropriate peak inspiratory pressure was set to create a tidal volume of 8 ml/kg in patients who would be ventilated with PCV mode. The number of breaths (Dräger Primus) was adjusted to provide an end-tidal carbon dioxide concentration (etCO2) level of 30-35 mmHg. PEEP was set to 5 cmH2O. Lung ultrasonography was performed at 4 different time periods. Modified lung ultrasonography scores of 12 quadrants were recorded. **Name:** Pressure controlled ventilation (PCV) mode **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** Comparison of the total lung ultrasonography score of 12 quadrants before extubation between groups in terms of atelectasis. **Measure:** Volume-controlled (VCV ) and pressure-controlled (PCV) respiratory ventilation modes modified lung ultrasonography scores before extubation **Time Frame:** Before extubation #### Secondary Outcomes **Description:** Determining the frequency of atelectasis in all quadrants before laryngeal mask airway (LMA) (preoperative period) and comparing it between the two groups **Measure:** Volume-controlled (VCV ) and pressure-controlled (PCV) respiratory ventilation modes **Time Frame:** Before LMA (preoperative period) **Description:** Determining the frequency of atelectasis in all quadrants in the 10th minute after LMA and comparing it between the two groups **Measure:** Volume-controlled (VCV ) and pressure-controlled (PCV) respiratory ventilation modes **Time Frame:** 10th minute after LMA **Description:** Determining the frequency of atelectasis in all quadrants in the 10th minute after extubation and comparing it between the two groups **Measure:** Volume-controlled (VCV ) and pressure-controlled (PCV) respiratory ventilation modes **Time Frame:** 10th minute after extubation **Description:** The frequency of atelectasis in all lung quadrants in the pre-LMA period, at the 10th minute after LMA, in the pre-extubation period, and at the 10th minute after extubation will be determined and compared. **Measure:** Comparison of atelectasis incidence and modified Lung ultrasonography (USG) scores in 12 different lung regions of patients followed in VCV/PCV ventilation modes under general anesthesia **Time Frame:** pre-LMA period (preoperative period), 10th minute after LMA, pre-extubation period, 10th minute after extubation **Description:** Effect of different ventilation modes on lung pressures (peak pressure cmH2O, plat pressure cmH2O, and mean pressure cmH2O parameters. **Measure:** The effects of these ventilation modes on lung pressures parameters. **Time Frame:** 10th minute after LMA, pre-extubation period ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Aged between 2 and 10 * American Society of Anesthesiologists (ASA) Scoring I-II * Elective surgery planned * Cases that will undergo general anesthesia * Surgical time is expected to be \>30 minutes Exclusion Criteria: * Patients who are allergic to ultrasonography (USG) gel * Known obstructive and restrictive lung disease * Pulmonary infection in the last 3 months * Having a history of surgery in the last 3 months * A history of multiple trauma in the last 3 months * Body Mass Index ≥30 * With diaphragmatic hernia * Having undergone laparoscopic abdominal surgery **Maximum Age:** 120 Months **Minimum Age:** 24 Months **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Ahmet Aras, MD **Phone:** 00905373222505 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Aslı Dönmez, Full Prof **Phone:** 00905322256473 **Role:** CONTACT #### Locations **Location 1:** **City:** Yenimahalle **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Ahmet Aras, MD - **Phone:** 00905373222505 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Asli Dönmez, Full Prof - **Phone:** 00905322256473 - **Role:** CONTACT **Country:** Turkey **Facility:** Ahmet Aras **State:** Ankara **Status:** RECRUITING **Zip:** 06170 #### Overall Officials **Official 1:** **Affiliation:** Republic of Türkiye Ministry of Health Ankara Etlik City Hospital **Name:** Ahmet Aras, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M4567 - Name: Pulmonary Atelectasis - Relevance: HIGH - As Found: Atelectasis - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001261 - Term: Pulmonary Atelectasis ### Intervention Browse Module - Browse Branches - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M4107 - Name: Anesthetics - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06430216 **Brief Title:** [Trial of device that is not approved or cleared by the U.S. FDA] **Official Title:** [Trial of device that is not approved or cleared by the U.S. FDA] #### Organization Study ID Info **ID:** 129-1346-01 #### Organization **Full Name:** [Redacted] ### Status Module **Delayed Posting:** True #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-21 **Overall Status:** WITHHELD #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Lead Sponsor **Name:** [Redacted] #### Responsible Party **Old Name Title:** [Redacted] **Old Organization:** [Redacted] ## Derived Section ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06430203 **Brief Title:** Indigenous Youth and Young Adults With Diabetes Peer Mentorship Program **Official Title:** Indigenous Youth and Young Adults With Diabetes Peer Mentorship Program #### Organization Study ID Info **ID:** 2025-10728 #### Organization **Class:** OTHER **Full Name:** McGill University Health Centre/Research Institute of the McGill University Health Centre ### Status Module #### Completion Date **Date:** 2028-09-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-29 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-24 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2028-04-01 **Type:** ESTIMATED #### Start Date **Date:** 2024-09-01 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-16 **Study First Submit QC Date:** 2024-05-23 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** McGill University Health Centre/Research Institute of the McGill University Health Centre #### Responsible Party **Investigator Affiliation:** McGill University Health Centre/Research Institute of the McGill University Health Centre **Investigator Full Name:** Romina Pace **Investigator Title:** Assistant Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The goal of this study is to learn if an Indigenous led peer-mentor program can provide Indigenous youth and young adults with the support needed to improve their distress and improve their diabetes control. Also, we will learn about Indigenous youth and young adults experience with diabetes. * Can a peer-mentoring program reduce diabetes distress among Indigenous youth and young adults with diabetes? * What is it like for Indigenous youth and young adults to be live with diabetes? * Can a peer-mentoring program reduce global distress and improve resilience among Indigenous youth and young adults with diabetes? * Can a peer-mentoring program lead to changes in lifestyle (diet, physical activity, substance use) and diabetes related clinical outcomes among Indigenous youth and young adults with diabetes. Researchers will compare distress, resilience, lifestyles, and diabetes related clinical outcomes before participating in the peer-mentoring program and at 6 and 12 months into the program. Additionally, participants will be asked to share their journey with diabetes through photos throughout the program Participants will: * Be paired with peer-mentors who also have diabetes and they will share their journey with diabetes * Participate in activities (grocery tours, walking clubs, land-based activities, cooking classes) held by peer-mentors * Complete questionnaires on distress, resilience, and lifestyle every 6 months. * Participate in Photovoice workshops to share their stories through pictures. **Detailed Description:** The rates of diabetes are increasing among youth and young adults. This rise is particularly steep among Indigenous peoples who also face high rates of depression and emotional distress due to the ongoing legacy of colonization resulting in systemic racism and intergenerational trauma. Diabetes care includes many aspects of self-care (checking sugar, taking medication, following exercise and diet advice), which is negatively impacted by emotional distress. The emotional distress specific to living with diabetes, known as diabetes distress (DD), is due to feeling overwhelmed by the demands of self-care, fears of complications, and guilt or shame over lifestyle choices. DD is known to be related to decreased wellbeing and poor diabetes control. The rate of DD has not been studied among Indigenous youth, nor have interventions aimed at reducing it to improve diabetes management. Peer support has been shown to help empower youth and young adults by normalizing their experiences and providing a safe space to express themselves. In the Eeyou Istchee Cree community in Quebec, Jonathan Linton, an Indigenous young adult with diabetes, developed a program for youth with diabetes on management and self-care for diabetes that incorporates traditional elements. As he helps participants be more active and eat healthier, he supports them in their journey with diabetes and creates a safe space for them to voice concerns, easing their distress. This research study will build on the initiative developed by Mr. Linton to create a community of peer-mentors to provide Indigenous youth and young adults with the support needed to improve their distress and improve their diabetes control. To evaluate the program, a combination of questionnaires to assess changes in DD and other emotional factors, measures of diabetes outcomes (glycemia, blood pressure, weight), and Photovoice, a research tool that allows participants to use images to explain their experience with diabetes, will be used. ### Conditions Module **Conditions:** - Diabetes Mellitus - Distress, Emotional ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 40 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Peer-mentoring which will include land based activities, nutrition and physical activity teaching. **Intervention Names:** - Behavioral: Peer mentoring **Label:** Peer-mentoring **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Peer-mentoring **Description:** Indigenous young adult peer mentors who will develop and deliver the program based on needs and wants of our participants. The program will be built on their experience and ideas. They will be empowered to guide the program in the direction they see best for their communities. **Name:** Peer mentoring **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** Problem Areas in Diabetes (PAID) scale from 0-100, higher score means more distress **Measure:** Diabetes Distress **Time Frame:** 0,6 and 12 months #### Secondary Outcomes **Description:** 0 item Kessler Psychological Distress scale (K10), from 10-50, the higher the score the greater the global distress. **Measure:** Global Distress **Time Frame:** 0,6 and 12 months **Description:** Child and Youth Resilience Measure-Revised (CYRM-R), for 10-18 years old. Scale from 17-85, the higher the score the greater the resilience **Measure:** Resilience-Children **Time Frame:** 0,6 and 12 months **Description:** Adult Resilience Measure-Revised (ARM-R), for those \> 18 years. Scale from 17-85, the higher the score the greater the resilience **Measure:** Resilience-Adults **Time Frame:** 0,6 and 12 months **Description:** Weight (kg)/\[Height(m)\]\^2 **Measure:** Body Mass Index **Time Frame:** 0 and 12 months **Description:** Percent HbA1c **Measure:** Hemoglobin A1c **Time Frame:** 0 and 12 months **Description:** mg/mmol **Measure:** urine albumin to creatine ratio **Time Frame:** 0 and 12 months **Description:** mmol/L **Measure:** low density lipoprotein **Time Frame:** 0 and 12 months **Description:** mmHg **Measure:** Blood pressure **Time Frame:** 0 and 12 months **Description:** Developed by Cree Board of health to assess diet and physical activity. Not a scale **Measure:** Lifestyle questionnaire **Time Frame:** 0 and 12 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Age 10-29 years old Clinical diagnosis of diabetes or gestational diabetes Exclusion Criteria: Age \> 29 years old Not at risk of diabetes **Healthy Volunteers:** True **Maximum Age:** 29 Years **Minimum Age:** 10 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Sahar Fazeli **Phone:** (438) 860-6079 **Role:** CONTACT #### Overall Officials **Official 1:** **Affiliation:** MUHC-RI **Name:** Romina Pace **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000044882 - Term: Glucose Metabolism Disorders - ID: D000008659 - Term: Metabolic Diseases - ID: D000004700 - Term: Endocrine System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M7115 - Name: Diabetes Mellitus - Relevance: HIGH - As Found: Diabetes - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown - ID: M25403 - Name: Glucose Metabolism Disorders - Relevance: LOW - As Found: Unknown - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003920 - Term: Diabetes Mellitus ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06430190 **Brief Title:** Peginterferon α-2b Combined CO2 Laser in Condylomata Acuminata **Official Title:** A Prospective, Exploratory Study to Evaluate the Efficacy of Peginterferon α-2b Injection Combined With Carbon Dioxide(CO2) Laser in the Treatment of Condylomata Acuminata #### Organization Study ID Info **ID:** Peg IFN α- 2b treatment for CA #### Organization **Class:** OTHER **Full Name:** First People's Hospital of Hangzhou ### Status Module #### Completion Date **Date:** 2025-12 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-24 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2025-01 **Type:** ESTIMATED #### Start Date **Date:** 2024-05 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-24 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Zhangyu Bu #### Responsible Party **Investigator Affiliation:** First People's Hospital of Hangzhou **Investigator Full Name:** Zhangyu Bu **Investigator Title:** Attending Physician **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** This is a prospective, randomized, open-label, controlled study, aiming to enroll 30 patients with Condylomata Acuminata. The study consists of two phases: a treatment phase (Weeks W1-W12) and an observation phase (Weeks W13-W24). Eligible patients will be randomly allocated into three groups at a ratio of 1:1:1: Test Group 1, Test Group 2, or the Control Group. And clinical cure, recurrence rates, adverse events, vital signs, laboratory tests, drug exposure doses, premature withdrawals will be analyzed. ### Conditions Module **Conditions:** - Condylomata Acuminata **Keywords:** - Condyloma Acuminatum, Genital Warts, Peginterferon α-2b, Interferon, CO2 Laser ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 30 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Drug: Peginterferon α-2b injection - Other: CO2 laser **Label:** Lesional group **Type:** EXPERIMENTAL #### Arm Group 2 **Intervention Names:** - Drug: Peginterferon α-2b injection - Other: CO2 laser **Label:** Systemic group **Type:** EXPERIMENTAL #### Arm Group 3 **Intervention Names:** - Other: CO2 laser **Label:** Control group **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Lesional group **Description:** Participants receive CO2 laser treatment followed by local injection of 36mcg of Peginterferon α-2b directly into the base of each treated wart, repeated weekly for 12 weeks, and then followed for another 12 weeks. **Name:** Peginterferon α-2b injection **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Systemic group **Description:** Participants undergo CO2 laser treatment and then receive a weekly subcutaneous injection of 180mcg of Peginterferon α-2b for 12 weeks, and then followed for another 12 weeks. **Name:** Peginterferon α-2b injection **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Control group - Lesional group - Systemic group **Description:** On the day (baseline), CO2 laser treatment was performed to remove all warts, and the treatment range was 0.2cm around the lesion and the depth was up to the dermis. Wound disinfection after laser. Participants are treated with CO2 laser therapy only and are observed for 12 weeks, followed by another 12-week observation period without any additional adjuvant therapy. **Name:** CO2 laser **Type:** OTHER ### Outcomes Module #### Other Outcomes **Measure:** Adverse events **Time Frame:** from baseline to 24 weeks. #### Primary Outcomes **Measure:** Clinical cure rate **Time Frame:** Week 12 #### Secondary Outcomes **Measure:** Recurrence rate **Time Frame:** Week 24 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients must be between 18 and 65 years old. * Patients with positive of human papillomavirus(HPV) nucleic acid test and acetowhite test, were diagnosed as condyloma acuminatum according to clinical manifestations and epidemiological history. * Patients' lesions are located on non-cavity areas such as the foreskin, glans penis, labia majora, labia minora, with a number ranging from 1 to 5 individual lesions, and each individual lesion having a diameter less than 1 centimeter. * For female participants with reproductive capability, a negative pregnancy test result is mandatory at the screening stage. * Participants must volunteer to enroll in the study and be able to understand and sign a written informed consent form. Exclusion Criteria: * Pregnant women, breastfeeding mothers, or individuals planning to conceive during the study period. * Patients who received treatment for genital warts within two weeks prior to screening. * Patients with concurrent skin conditions in the affected area that might significantly impact the evaluation of treatment efficacy. * Individuals with known severe immunodeficiency or those requiring long-term use of corticosteroids and immunosuppressive agents. * Active carriers of hepatitis B virus, hepatitis C virus, human immunodeficiency virus (HIV), or Treponema pallidum (syphilis). * Patients with a history of severe cardiovascular, hepatic, renal, endocrine, digestive, immune, respiratory, or nervous system diseases. * Patients with severe retinal disorders or other serious ophthalmologic conditions. * Patients allergic to interferons or excipients in the medication formulation, or those deemed unsuitable for CO2 laser treatment. * Individuals meeting any contraindications listed in the investigational drug's package insert. * Patients who participated in another interventional clinical trial within three months before screening, or those planning to participate in another clinical trial during the study period. * Other cases deemed inappropriate for enrollment by the investigator due to various reasons. **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Hangzhou **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Zhangyu Bu - **Phone:** 0571-56005600 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Kune Lu - **Phone:** 0571-56005600 - **Role:** CONTACT **Country:** China **Facility:** Hangzhou First People's Hospital **State:** Zhejiang **Zip:** 310006 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000015229 - Term: Sexually Transmitted Diseases, Viral - ID: D000012749 - Term: Sexually Transmitted Diseases - ID: D000003141 - Term: Communicable Diseases - ID: D000007239 - Term: Infections - ID: D000014860 - Term: Warts - ID: D000030361 - Term: Papillomavirus Infections - ID: D000004266 - Term: DNA Virus Infections - ID: D000014777 - Term: Virus Diseases - ID: D000017193 - Term: Skin Diseases, Viral - ID: D000014412 - Term: Tumor Virus Infections - ID: D000091662 - Term: Genital Diseases - ID: D000091642 - Term: Urogenital Diseases - ID: D000012874 - Term: Skin Diseases, Infectious - ID: D000012871 - Term: Skin Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M6443 - Name: Condylomata Acuminata - Relevance: HIGH - As Found: Condylomata - ID: M17603 - Name: Warts - Relevance: LOW - As Found: Unknown - ID: M15558 - Name: Sexually Transmitted Diseases - Relevance: LOW - As Found: Unknown - ID: M17933 - Name: Sexually Transmitted Diseases, Viral - Relevance: LOW - As Found: Unknown - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M23687 - Name: Papillomavirus Infections - Relevance: LOW - As Found: Unknown - ID: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M7442 - Name: DNA Virus Infections - Relevance: LOW - As Found: Unknown - ID: M15674 - Name: Skin Diseases - Relevance: LOW - As Found: Unknown - ID: M19501 - Name: Skin Diseases, Viral - Relevance: LOW - As Found: Unknown - ID: M17162 - Name: Tumor Virus Infections - Relevance: LOW - As Found: Unknown - ID: M2876 - Name: Genital Diseases - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M15677 - Name: Skin Diseases, Infectious - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003218 - Term: Condylomata Acuminata ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M10407 - Name: Interferons - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06430177 **Brief Title:** The Effect of Sujok Therapy on Patient Comfort, Pain Intensity, and Anxiety Level in Cancer Patients With Port Catheter Placement **Official Title:** The Effect of Sujok Therapy on Patient Comfort, Pain Intensity, and Anxiety Level in Cancer Patients With Port Catheter Placement: A Randomized, Placebo and Controlled Study #### Organization Study ID Info **ID:** 2024/07-28 #### Organization **Class:** OTHER **Full Name:** Firat University ### Status Module #### Completion Date **Date:** 2024-12-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-29 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-24 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2024-09-01 **Type:** ESTIMATED #### Start Date **Date:** 2024-06-01 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Firat University #### Responsible Party **Investigator Affiliation:** Firat University **Investigator Full Name:** Gülcan Bahçecioğlu Turan **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Cancer is a fatal disease characterized by uncontrolled growth and proliferation of tissues and organs in the human body. Among cancer treatments, chemotherapy is the most commonly used treatment method. The drugs used in chemotherapy cause vascular toxic effects during administration, frequent blood samples taken from the patient, antibiotic treatments applied, parenteral nutrition treatments. Subcutaneous venous port catheter (SCVPK), which is a permanent and long-term vascular access route that can be used for medical purposes and in emergency situations, is a frequently preferred and safe intravenous access route because it is not visible outside the body, is well tolerated by the patient, and has a low risk of infection. However, invasive procedures such as port needle insertion and replacement can also cause pain, anxiety and changes in vital signs in patients. Nowadays, the use of non-pharmacological approaches as well as pharmacological methods is increasing in the management of symptoms such as anxiety before the invasive procedure and pain during application in patients receiving chemotherapy treatment. These approaches improve the quality of life of patients and have a positive physiological effect. One of these approaches is sujok therapy. In Su Jok application; The reflection points of the organs are on the hands and feet. These points reflect to the body organ in that area and healing occurs. By finding the right point, energy flow is provided by massaging with appropriate applicators. This research will be conducted to examine the effect of Sujok therapy on pain intensity and anxiety level in cancer patients who have undergone port catheter placement. The research will be conducted as a randomized experimental and placebo study with a pretest-posttest control group in the oncology service of Fethi Sekin City Hospital. 90 (30 experimental, 30 control, 30 placebo) cancer patients who accept the research and meet the sample criteria of the study will be subjected to port catheter application. Application areas for pain, anxiety and stress before the port catheter to the patients in the experimental group will be determined with the help of a probe (diagnostic stick), and seeds will be added to these points approximately 45 minutes before the application and fixed with a patch. For cancer patients in the placebo group, the same procedure will be performed with seeds that have a neutral effect on the body. No procedure will be applied to the patients in the control group. Patient Information Form, General Comfort Scale (GAS), Visual Analog Scale -Pain (VAS-P), Visual Analog Scale -Anxiety (VAS-A) and State-Trait Anxiety Scale were used as data collection tools. (DSKÖ) scale will be used. SPPS 21.0 (Statistical Programme for Social Sciences) package program will be used to evaluate the data obtained from the research. It is thought that if the objectives of the study are achieved, it will help reduce the level of pain and anxiety that may occur during and after port catheter application. In addition, it will contribute to the professional advancement of the project manager, which is a career development project. The positive results in this study will guide other interventions to increase the comfort level of cancer patients who will undergo port catheterization and reduce the level of pain and anxiety. ### Conditions Module **Conditions:** - Cancer - Chemotherapy Effect **Keywords:** - Su Jok - Pain - Anxiety ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 90 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Su Jok will be done **Intervention Names:** - Behavioral: Su Jok **Label:** Experimental **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Su Jok will be done **Intervention Names:** - Behavioral: Su Jok **Label:** Placebo **Type:** SHAM_COMPARATOR #### Arm Group 3 **Label:** Control **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Experimental - Placebo **Description:** Su Jok will be done **Name:** Su Jok **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** It is a four-point Likert type consisting of 48 items to measure the expected comfort result of the patient in order to test the taxonomic structure created after completing the conceptual studies of comfort. In this research, the scale adapted to Turkish by Kuğuoğlu and Karabacak was used. The scale is a four/six point Likert type and contains a total of 48 items. A four-point Likert type was preferred in the study due to its ease of use. Scale sub-dimensions; relief (16 items), relaxation (17 items) and overcoming problems (15 items). The response patterns of the scale, which consists of positive and negative items, are given in mixed order. Accordingly, in positive statements, a high score (4p) indicates high comfort, a low score (1p) indicates low comfort, in negative items, a low score (1p) indicates high comfort, and a high score (4p) indicates low comfort. In the evaluation of the scale; The negative scores obtained are reverse coded and added to the positive items. **Measure:** General Comfort Scale **Time Frame:** two hours later **Description:** The patients were asked to measure their anxiety level during rest or activity on a 10 cm long horizontal line. is requested to show. The value 0 is at the beginning of the line and 10 is at the end. 10 indicates extreme anxiety, 0 indicates not at all. It shows that there is no concern. VAS scale is used quite frequently during the evaluation of anxiety severity. is used **Measure:** Visual Analog Scale - Anxiety **Time Frame:** two hours later **Description:** It is used to convert some values that cannot be measured numerically into numerical values. Two extreme definitions of the parameter to be evaluated are written at both ends of a 100 mm line, and the patient is asked to indicate where his/her situation is appropriate on this line by drawing a line, placing a dot, or pointing. **Measure:** Visual Analog Scale -Agrı **Time Frame:** two hours later **Description:** It is a scale developed to measure individuals' state and trait anxiety levels. It is a self-assessment scale whose Turkish validity and reliability studies have been conducted. In this study, the section of the scale measuring state anxiety was used to determine the state anxiety levels of the patients. State Anxiety Scale is a 4-point Likert type with 20 items and is scored according to the severity of the feelings, thoughts or behaviors expressed by the items as "not at all": 1, "somewhat": 2, "a lot": 3, "completely": 4. . The scale includes directly or reverse scored expressions. **Measure:** State-Trait Anxiety Scale **Time Frame:** two hours later ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Being over 18 years of age * Ability to communicate adequately * Being diagnosed with cancer * Will receive chemotherapy treatment * Port catheter placement will be performed * Suitable for Implantable Port Catheter Placement Exclusion Criteria: * Loss of sensation in the hands, amputation, injury, etc. that would prevent practice. to be * Patients with chronic pain or anxiety disorders, using any analgesics or anxiolytics **Healthy Volunteers:** True **Maximum Age:** 85 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Gülcan Bahçecioğlu Turan **Phone:** 05065576086 **Role:** CONTACT **Contact 2:** **Name:** Necla Yıldırım **Phone:** 0551 553 28 58 **Role:** CONTACT #### Locations **Location 1:** **City:** Elazığ **Country:** Turkey **Facility:** Fırat university **State:** Center **Zip:** 25240 ### IPD Sharing Statement Module **Description:** It will be shared after it is finished **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009461 - Term: Neurologic Manifestations ### Condition Browse Module - Browse Branches - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC10 - Name: Nervous System Diseases ### Condition Browse Module - Browse Leaves - ID: M4324 - Name: Anxiety Disorders - Relevance: LOW - As Found: Unknown - ID: M13066 - Name: Pain - Relevance: HIGH - As Found: Pain Intensity - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000010146 - Term: Pain ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06430164 **Brief Title:** AB Gait Estim Neurophysiology **Official Title:** Effects of Gait Training Strategies and Noninvasive Stimulation on Neurophysiology and Walking Performance in Able-Bodied Adults- A Preliminary Study #### Organization Study ID Info **ID:** STUDY00007235 #### Organization **Class:** OTHER **Full Name:** Emory University ### Status Module #### Completion Date **Date:** 2026-12 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-21 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2026-12 **Type:** ESTIMATED #### Start Date **Date:** 2024-02-12 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Emory University #### Responsible Party **Investigator Affiliation:** Emory University **Investigator Full Name:** Trisha Kesar **Investigator Title:** Associate Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** True **Is FDA Regulated Drug:** False **Is US Export:** True **Oversight Has DMC:** True ### Description Module **Brief Summary:** This study is being done to answer the question: What are the effects of electrical stimulation and stepping practice on connections between the brain and muscles? The long-term goal of this project is to develop novel, effective, and personalized rehabilitation protocols founded on an understanding of neurobiological mechanisms that combine electrical stimulation with gait training to improve gait performance in older adults and stroke survivors. The rationale of this project is to explore and generate preliminary data regarding how electrical stimulation-based strategies modulate cortical and spinal circuits in able-bodied individuals. The researchers will evaluate the effects of short treadmill walking bouts or single gait training sessions with and without electrical stimulation on somatosensory, spinal-reflex, corticospinal circuit neurophysiology, and/or gait performance. The study will provide important preliminary and normative data that can explain how brain circuits change with stimulation or stepping practice and inform future rehabilitation studies on patients. The study population is able-bodied individuals. **Detailed Description:** This study is being done to determine the effects of electrical stimulation and walking practice on connections between the brain and muscles. This study consists of 1-5 study visits lasting up to 5 hours each. Participants will complete stepping training with or without electrical stimulation delivered to their leg muscles; noninvasive stimulation will be delivered to the participants' brain or nerves in the leg to measure the strength of connections within their brain and between their brain / spinal cord and their muscles. ### Conditions Module **Conditions:** - Gait **Keywords:** - Corticospinal excitability - Non-invasive stimulation - Functional electrical stimulation (FES) ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** OTHER #### Enrollment Info **Count:** 50 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants will participate in 2 to 5 sessions over 2-8 weeks. Each session will comprise gait or stepping practice on a treadmill with functional electrical stimulation, and non-invasive measurement of neural circuit excitability. Participants will complete multiple 30-second to 4-minute bouts of walking on the treadmill or overground at speeds ranging from self-selected to fast speeds (faster than comfortable self-selected speed), with rest breaks between bouts. For gait training, participants may complete up to six 6-minute bouts of walking with rest breaks between bouts (30-36 minutes walking). **Intervention Names:** - Other: Gait Training - Device: Functional electrical stimulation (FES) **Label:** Gait with functional electrical stimulation **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Participants will participate in 2 to 5 sessions over 2-8 weeks. Each session will comprise gait or stepping practice on a treadmill without functional electrical stimulation, and non-invasive measurement of neural circuit excitability. Participants will complete multiple 30-second to 4-minute bouts of walking on the treadmill or overground at speeds ranging from self-selected to fast speeds (faster than comfortable self-selected speed), with rest breaks between bouts. For gait training, participants may complete up to six 6-minute bouts of walking with rest breaks between bouts (30-36 minutes walking). **Intervention Names:** - Other: Gait Training **Label:** Gait without functional electrical stimulation **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Participants will participate in a single session of peripheral electrical stimulation paired with cortical stimulation pulses (i.e. paired associative stimulation(PAS)) on somatosensory, spinal-reflex, and corticospinal neurophysiology. **Intervention Names:** - Other: Gait Training - Device: Peripheral electrical stimulation paired with cortical stimulation pulses **Label:** Paired stimulation of the cortex and peripheral nervous system **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Gait with functional electrical stimulation - Gait without functional electrical stimulation - Paired stimulation of the cortex and peripheral nervous system **Description:** Gait training: One or multiple short bouts of stepping practice on a treadmill at self-selected or fast speeds will be delivered without FES. **Name:** Gait Training **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - Gait with functional electrical stimulation **Description:** Electrical stimulation involving the parameters and settings proposed here is commonly used in clinical practice and research for pain relief and other applications also referred to as neuromuscular or transcutaneous electrical nerve stimulation. The FES will be delivered using the UDel Stimulator, a custom-designed FES system from the University of Delaware FES lab. Researchers will use a customized, real-time system to control the stimulator and deliver stimulation during appropriate phases of the gait cycle. Stimulation will be delivered to the ankle dorsiflexors when the subject's foot is in the air (swing phase). Stimulation will be delivered to the ankle plantarflexors during the terminal stance phase of gait. 30-Hz variable frequency stimulation trains will be delivered during gait. **Name:** Functional electrical stimulation (FES) **Other Names:** - FES **Type:** DEVICE #### Intervention 3 **Arm Group Labels:** - Paired stimulation of the cortex and peripheral nervous system **Description:** Paired associative stimulation (PAS) on somatosensory, spinal-reflex, and corticospinal neurophysiology delivered with different stimulation parameters. The PAS sessions will be conducted in a static posture (seated or standing). **Name:** Peripheral electrical stimulation paired with cortical stimulation pulses **Type:** DEVICE ### Outcomes Module #### Other Outcomes **Description:** To record muscle activity, small electromyography (EMG) sensors may be attached to various muscles. The EMG sensors will be attached using hypo-allergenic adhesive. EMG signals will be recorded from the following muscles: tibialis anterior, soleus, gastrocnemius, quadriceps femoris, hamstrings, gluteus medius, and erector spinae **Measure:** Muscle activity during gait **Time Frame:** Pretest (up to 60 seconds), during test (up to 36 minutes), post-test (up to 60 seconds) **Description:** Somatosensory transmission and excitability may be assessed using electroencephalography (EEG) responses to peripheral nerve stimulation (PNS) stimuli delivered to the lower limb. **Measure:** Somatosensory excitability **Time Frame:** Pretest (up to 60 seconds), during test (up to 36 minutes), post-test (up to 60 seconds) #### Primary Outcomes **Description:** Marker data will be collected using a 7-camera motion analysis system at 120 Hz (Vicon, Oxford, UK). During treadmill walking, ground reaction forces during treadmill walking will be collected using a treadmill instrumented with two 6-component force platforms under each belt (Bertec, USA). Ground reaction forces will be collected using a force plate embedded within the lab floor (AMTI, USA). **Measure:** Gait Performance **Time Frame:** Pretest (up to 60 seconds), during test (up to 36 minutes), post-test (up to 60 seconds) **Description:** Corticospinal excitability will be assessed using a non-invasive technique called transcranial magnetic stimulation (TMS). TMS will be delivered using MagStim Stimulators with a double circular coil, custom-built double-cone, or batwing coil (Magstim Ltd, Wales, UK). Electrical activity from muscles in response to the TMS will be collected using surface EMG electrodes attached to muscles that play critical roles during walking (e.g., quadriceps femoris, tibialis anterior, soleus, gastrocnemius, hamstrings, etc.). In addition, EMG signals may be recorded from a couple of upper extremity muscles (e.g., first dorsal interosseus, flexor digitorum indicis) to be used as a control. **Measure:** Corticospinal excitability **Time Frame:** Pretest (up to 60 seconds), during test (up to 36 minutes), post-test (up to 60 seconds) **Description:** Spinal excitability may be assessed using peripheral electrical stimulation delivered to the nerves innervating the ankle muscles. The methods for electrical stimulation are similar to those used for delivering functional electrical stimulation except that the subjects are seated and the stimulation is used to obtain outcome measures assessing spinal excitability. Muscles of interest are the soleus and medial gastrocnemius (calf muscles), and tibialis anterior (front of lower leg). EMG activity will be recorded while 50-60 electrical stimuli (short 1 ms square pulses, ranging in intensity from 1mA - 80 mA), 7-10 seconds apart, are delivered to the muscle. Researchers may also deliver 5-20 electrical stimulus pulses at intensities that elicit a percentage of the maximum reflex response. **Measure:** Spinal circuit excitability **Time Frame:** Pretest (up to 60 seconds), during test (up to 36 minutes), post-test (up to 60 seconds) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * 18-65 years * Able-bodied (healthy without any physical disability, neurological, orthopedic, or other medical disorder affecting walking or study protocol participation) * Ability to walk \>10m overground and for 1 minute on a treadmill * Ability to follow 3-stage commands and provide informed consent. Exclusion Criteria: * Self-reported history or evidence of orthopedic or physical disability * History or evidence of neurological pathology * Pregnancy (female) * Uncontrolled hypertension * Cardiac pacemaker or other implanted electronic system * Presence of skin conditions preventing electrical stimulation setup * Impaired sensation in the left upper limb. * Bruises or cuts at the stimulation electrode placement site * Concurrent enrollment in rehabilitation or another investigational study. * History or evidence of orthopedic or physical disability interfering with study procedures * History or evidence of neurological pathology or disorder * Severe uncontrolled medical problems (e.g., hypertension, cardiovascular disease, rheumatoid arthritis, active cancer or renal disease, epilepsy) that may interfere with study procedures * Contraindications to TMS such as metal implants, medications that can increase cortical excitability, unexplained dizziness in the past 6 months **Healthy Volunteers:** True **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Trisha Kesar, PT, PhD **Phone:** 404-712-5803 **Role:** CONTACT #### Locations **Location 1:** **City:** Atlanta **Country:** United States **Facility:** Emory University **State:** Georgia **Status:** RECRUITING **Zip:** 30329 #### Overall Officials **Official 1:** **Affiliation:** Emory University **Name:** Trisha Kesar, PT, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Access Criteria:** Requests sent to PI with supporting documentation. **Description:** Researchers will share group deidentified data. **IPD Sharing:** YES **Time Frame:** Within two years after study completion and in conjunction with peer-reviewed publication ## Derived Section ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06430151 **Brief Title:** Useability and Acceptability of the CUE1 Device in Older People With Parkinson's Disease **Official Title:** Useability and Acceptability of the CUE1 Device in Older People With Parkinson's Disease #### Organization Study ID Info **ID:** A096551 #### Organization **Class:** OTHER **Full Name:** Cambridge University Hospitals NHS Foundation Trust ### Status Module #### Completion Date **Date:** 2024-12-16 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-21 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-11-16 **Type:** ESTIMATED #### Start Date **Date:** 2024-05-16 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-16 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Dr Alistair Mackett #### Responsible Party **Investigator Affiliation:** Cambridge University Hospitals NHS Foundation Trust **Investigator Full Name:** Dr Alistair Mackett **Investigator Title:** Consultant Geriatrician **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The CUE1 device is a non-invasive wearable device for people with Parkinson's Disease (PD) approved for sale in the UK. The CUE1 device utilises two established methods to improve motor symptoms in PD, namely pulsed cueing and vibrotactile stimulation. Many people with PD wish to explore non-pharmacological interventions as an adjunct to manage their motor symptom. Study design and eligibility: This feasibility study is to establish whether the CUE1 device is a useable and acceptable device for older people with PD. 20-25 participants aged \>60 years with PD will be recruited from a movement disorder service to the study. Methodology: Participants will undertake baseline assessments of motor symptoms and quality of life with a PD nurse assessor in their own home. Following this the CUE1 device will be fitted and repeat assessments of motor symptoms will take place after 20 minutes. The participants will complete a daily diary of useability and acceptability for 4 weeks. A second visit will occur at 4 weeks with the same PD nurse assessor where the final set of motor symptom and quality of life assessments will be completed. ### Conditions Module **Conditions:** - Parkinson Disease ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP **Intervention Model Description:** Useability and acceptability study of a vibrotactile stimulation device ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 20 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Device: CUE1 **Label:** CUE1 users **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - CUE1 users **Description:** Sternal worn focused vibrotactile stimulation and cueing device **Name:** CUE1 **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Participants' completion of a patient diary which will collect safety, tolerability, useability, and efficacy reports of the device over the study period. Participants will also complete a Patient Global Impression of Change (PGI-C) questionnaire at the end of the study. **Measure:** Useability and acceptability of the CUE1 device in older people with Parkinson's disease **Time Frame:** 4 weeks #### Secondary Outcomes **Description:** Completion of validated motor scores during the study period to evaluate feasibility of the data collection method for motor symptom change. Any signals of improvement in motor scores would potentially justify larger randomised controlled studies to evaluate this systematically. **Measure:** To undertake standardized, validated measurements of motor function with use of the CUE1 device **Time Frame:** 4 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Individuals under the care of a Cambridge University Hospitals Foundation Trust movement disorder service with an established clinical diagnosis of Parkinson's disease based on the UK Brain bank criteria Exclusion Criteria: 1. Co-existing significant neurological disorder (disabling stroke, multiple sclerosis, dementia, motor neurone disease), 2. Atypical parkinsonian disorder diagnosis (e.g. multiple systems atrophy, progressive supranuclear palsy or cortical basal degeneration syndrome) 3. co-existing physical impairment or disability causing significant mobility impairment (severe lower limb osteoarthritis) 4. trauma or pain to the sternum 5. use of other medical device e.g. pacemaker, deep brain stimulator, TENS machine etc 6. lacking capacity to consent to the study 7. Sensitivity to medical adhesives 8. Existing participant in intervention research trial **Maximum Age:** 100 Years **Minimum Age:** 60 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Alistair J Mackett, MBBS **Phone:** 01223 217483 **Role:** CONTACT #### Locations **Location 1:** **City:** Cambridge **Contacts:** ***Contact 1:*** - **Name:** Alistair J Mackett, MBBS - **Phone:** 01223 217483 - **Role:** CONTACT **Country:** United Kingdom **Facility:** Cambridge University Hospitals Foundation Trust **Status:** RECRUITING ### IPD Sharing Statement Module **Description:** No plans to make IPD available to other researchers **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020734 - Term: Parkinsonian Disorders - ID: D000001480 - Term: Basal Ganglia Diseases - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000009069 - Term: Movement Disorders - ID: D000080874 - Term: Synucleinopathies - ID: D000019636 - Term: Neurodegenerative Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases ### Condition Browse Module - Browse Leaves - ID: M13213 - Name: Parkinson Disease - Relevance: HIGH - As Found: Parkinson's Disease - ID: M22494 - Name: Parkinsonian Disorders - Relevance: LOW - As Found: Unknown - ID: M25603 - Name: Ganglion Cysts - Relevance: LOW - As Found: Unknown - ID: M16358 - Name: Synovial Cyst - Relevance: LOW - As Found: Unknown - ID: M4774 - Name: Basal Ganglia Diseases - Relevance: LOW - As Found: Unknown - ID: M5204 - Name: Brain Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M12029 - Name: Movement Disorders - Relevance: LOW - As Found: Unknown - ID: M2217 - Name: Synucleinopathies - Relevance: LOW - As Found: Unknown - ID: M21558 - Name: Neurodegenerative Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000010300 - Term: Parkinson Disease ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06430138 **Acronym:** ORANGUT **Brief Title:** Bioavailability and Bioactivity of Orange Polyphenols **Official Title:** Bioavailability and Bioactivity of Orange Polyphenols on Gut Health #### Organization Study ID Info **ID:** REC/24/0002 #### Organization **Class:** OTHER **Full Name:** University of Ulster ### Status Module #### Completion Date **Date:** 2024-12-13 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-22 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-09-13 **Type:** ESTIMATED #### Start Date **Date:** 2024-04-26 **Type:** ACTUAL **Status Verified Date:** 2024-04 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-04-23 **Study First Submit QC Date:** 2024-05-22 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** Andalusian Institute of Agricultural and Fisheries Research and Training (IFAPA) #### Lead Sponsor **Class:** OTHER **Name:** University of Ulster #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study will provide a greater insight into the relationship between orange consumption and health (particularly gut health) and could be used to help with the development of novel food products. Oranges are a rich source of (poly)phenols, and although the advantages of a (poly)phenol-rich diet are well-established, the bioavailability and bioactivity of orange (poly)phenols in the context of human digestion are poorly understood. This study will address this gap in research. **Detailed Description:** This study will provide a greater insight into the relationship between orange consumption and health (particularly gut health) and could be used to help with the development of novel food products. Oranges are a rich source of (poly)phenols, and although the advantages of a (poly)phenol-rich diet are well-established, the bioavailability and bioactivity of orange (poly)phenols in the context of human digestion are poorly understood. Until recently, analysis of biofluids with HPLC-MS revealed relatively simple phenolic profiles. However, with current high resolution (HR)-MS instrumentation detection limits and selectivity have improved greatly and HPLC-HR-MS methodology is now the analytical method of choice. Consequently, the number of phenolics that can be monitored has increased markedly in recent years. A previous study, using validated methodology, identified 65 phenolic compounds in urine collected after ingestion of orange juice. In the proposed project it is planned to use such analytical methodology for targeted and untargeted metabolomics of flavanone metabolites and colonic catabolites in biofluids collected after consumption of orange juice by ileostomists and subjects with a functioning colon. Metabolomics refers to the measurement of metabolites present within a cell, tissue, or organism resulting from physiological stimulus - in the context of the current study, the stimulus is orange juice consumption. Untargeted metabolomics involves a comprehensive analysis of all measurable substances in a sample of unknown metabolites, and targeted metabolomics denotes the quantification of defined group(s) of metabolites. The particular value of including ileostomists in the study is that analysis of their ileal fluid and urine will provide valuable information on compounds derived from the ingested OJ flavanones, prior to digestion and absorption by the large intestine. Acute bioavailability feeding study in two groups; ileostomists and healthy adults. The study will take place in the Human Intervention Studies Unit (HISU), at Ulster University, Coleraine Campus. Prior to attending the HISU, participants will be asked to follow a restriction diet for 72 hours before the study and the 24 hours of the study day, which will involve the intake of food containing low levels of (poly)phenols. The participants will be provided with a restriction (low (poly)phenol) meal, which they will consume the evening before the study (at approximately 6 - 7.00pm) and fast until attending the HISU the following morning. This means no food will be taken overnight and no breakfast taken prior to attending the HISU. Low (poly)phenol foods will be provided to participants on the day of the study, and they will be asked to continue this restriction diet until all samples have been collected. Healthy participants and Ileostomists (N=20) will provide 10 blood samples and 3 urine samples over the study period. Blood samples: Upon arrival at the HISU, a qualified phlebotomist will fit a cannula, and collect a blood sample (0hr) (\~8ml). The participant will then be given the intervention; 300 ml of orange juice. A further 8 blood samples will be collected at 1hr intervals (1hr, 2hr, 3hr, 4hr, 5hr, 6hr, 7hr, 8hr). After the 8hr blood draw the cannula will be removed by the phlebotomist and the participant will be free to go home. They will return to the HISU the following morning to provide a final blood sample (24hr). Ten blood samples will be collected in total. Urine samples: Participants will start a 24-hour urine collection the day before the study day. They will be provided with a 2L urine container in advance of commencing the urine collection; participants will use this to deposit urine samples over the 24-hr period. Upon arrival at the HISU on the morning of the study, participants will return the urine container holding the -24 to 0 hr urine sample. Participants will complete two additional urine collections (0-8hr and 8-24hr samples), a fresh urine container will be provided at each time point. The 8-24hr sample will be returned by the participant when they return to the HISU to provide the 24hr blood sample. Ileostomist participants (n=10) will also provide three ileal samples over the study period. Ileal samples: Participants will be asked to refrain from emptying their stoma bag upon waking on the morning of the study. Upon arrival at the HISU, an ileal sample will be collected; the overnight stoma bag will be removed and replaced with a new stoma bag by the participant. Two additional ileal samples will be collected at 0-8 hr and 8-24 hrs, the stoma bag will be removed and replaced with a new stoma bag by the participant at each sampling point. The 8-24hr sample will be returned by the participant when they return to the HISU to provide the 24hr blood sample. Multiple stoma bags may be used by the participant as required. Height and weight measurements will also be taken for all participants (N=20), during their visit to the HISU. ### Conditions Module **Conditions:** - Healthy Nutrition **Keywords:** - Orange, - polyphenols - ileostomy ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** FACTORIAL **Intervention Model Description:** Acute intervention in populations with and without colon ##### Masking Info **Masking:** SINGLE **Masking Description:** Single Blind(with masked participant) **Who Masked:** - PARTICIPANT **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 20 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participant will be given Orange Juice 300ml to drink **Intervention Names:** - Dietary Supplement: 300ml Orange Juice **Label:** Healthy participants **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Participant will be given orange Juice 300ml to drink **Intervention Names:** - Dietary Supplement: 300ml Orange Juice **Label:** Ileostomy participants **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Healthy participants - Ileostomy participants **Description:** Acute intervention in populations with and without colon **Name:** 300ml Orange Juice **Type:** DIETARY_SUPPLEMENT ### Outcomes Module #### Primary Outcomes **Description:** Quantification of polyphenols via LC-MS/MS **Measure:** Quantification of circulating (blood) (poly)phenols and microbially derived metabolites in participants with colon compared to without colon (ileostomates). **Time Frame:** Change over 24 hours compared **Description:** Quantification of polyphenols via LC-MS/MS **Measure:** Quantification of urinary (poly)phenols and microbially derived metabolites in participants with colon compared to without colon (ileostomates). **Time Frame:** Change over 24 hours ] #### Secondary Outcomes **Description:** Mass spectrometry analysis of In vitro gut model colonic fermentation of ileal fluid (µmol/L) **Measure:** ileal fluid polyphenolic metabolites. **Time Frame:** Change over 24 hours **Description:** Mass spectrometry analysis of In vitro gut model colonic fermentation of ileal fluid (µmol/L) **Measure:** Ileal fluid microbial mediated metabolites **Time Frame:** Change over 24 hours ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: (ileostomates) * Adult with an ileostomy, ≥1.5-years post-operative * Aged 18-75 years at recruitment * Not pregnant / lactating * No learning or other disabilities * Not currently taking antibiotics * Not currently taking plant-based dietary supplements * Not currently taking any prescribed medications that would prevent overnight fasting Inclusion Criteria Healthy adults; no pre-existing chronic disease (GI related) * Aged 18-75 years at recruitment * Not pregnant / lactating * No learning or other disabilities * Not currently taking antibiotics * Not currently taking plant-based dietary supplements * Not currently taking any prescribed medications that would prevent overnight fasting Exclusion criteria (Ileostomates): * Adults \<18 or \>75 years at recruitment * Ileostomy, \<1.5 years post-operative * Pregnant/lactating females * Adults with learning or other disabilities * Citrus fruit (orange) allergy or sensitivity * Currently taking antibiotics * Currently taking plant-based dietary supplements * Currently taking any prescribed medications that would prevent overnight fasting Exclusion criteria (Healthy adults): * Adults \<18 or \>70 years at recruitment * Pregnant/lactating females * Adults with learning or other disabilities * Citrus fruit (orange) allergy or sensitivity * Currently taking antibiotics * Currently taking plant-based dietary supplements * Currently taking any prescribed medications that would prevent overnight fasting **Healthy Volunteers:** True **Maximum Age:** 75 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Prof Gill, PhD **Phone:** +44 28 7012 3181 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Ruth Price, PhD **Phone:** +442870123878 **Role:** CONTACT #### Locations **Location 1:** **City:** Coleraine **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Ruth Price, PhD - **Phone:** 00442870123878 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Geraldine Horigan, PhD - **Phone:** +44 2870 123043 - **Phone Ext:** 23043 - **Role:** CONTACT **Country:** United Kingdom **Facility:** Ulster University,Human Intervention Studies Unit, **State:** Co. Londonderry **Status:** RECRUITING **Zip:** BT521SA ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Intervention Browse Module - Browse Branches - Abbrev: HB - Name: Herbal and Botanical - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: T244 - Name: Orange - Relevance: HIGH - As Found: Self-monitoring - ID: T120 - Name: Cola - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06430125 **Brief Title:** Nephroprotective Effect of Nicorandil in Type 2 Diabetes Mellitus **Official Title:** Clinical Study Evaluating the Nephroprotective Effect of Nicorandil in Patients With Type 2 Diabetes Mellitus #### Organization Study ID Info **ID:** Nicorandil Nephroprotective #### Organization **Class:** OTHER **Full Name:** Tanta University ### Status Module #### Completion Date **Date:** 2025-02 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-21 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2025-02 **Type:** ESTIMATED #### Start Date **Date:** 2023-02-28 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Tanta University #### Responsible Party **Investigator Affiliation:** Tanta University **Investigator Full Name:** Mohammed Atta Ali El-Hazzab **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** This study aims to evaluate the possible nephroprotective effect of nicorandil in patients with type 2 diabetes mellitus . ### Conditions Module **Conditions:** - Type2 Diabetes Mellitus ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 46 **Type:** ESTIMATED **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** this group will include 23 patients who will receive metformin 2gm/day. The initial dose of metformin will be 1 g/day taken orally with the meal. After 7 days (week 1), the dose will be up titrated to daily dose of 2,000 mg/day. Treatment duration will be 12 weeks . **Label:** Control group **Type:** NO_INTERVENTION #### Arm Group 2 **Description:** this group will include 23 patients who will receive a combination of metformin 2g/day and nicorandil 10 mg twice daily. The initial dose of metformin will be 1 g/day taken orally with the meal. After 7 days (week 1), the dose will be uptitrated to daily dose of 2,000 mg/day. Treatment duration will be 12 weeks . **Intervention Names:** - Drug: Nicorandil 10 MG Oral Tablet **Label:** Nicorandil group **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Nicorandil group **Description:** Nicorandil 10 MG oral tablet twice daily **Name:** Nicorandil 10 MG Oral Tablet **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Patients wii undergo clinical assesment for progression of diabetic nephropathy as measured by KDIGO at baseline and after 12 weeks **Measure:** prevention of progression of kidney disease as measured by KDIGO. **Time Frame:** 12 weeks #### Secondary Outcomes **Description:** Venous blood will be collected before treatment and after 12 week . **Measure:** change in the serum concentrations of Kidney injury molecule 1(Kim-1). **Time Frame:** 12 weeks **Description:** Venous blood will be collected before treatment and after 12 week . **Measure:** change in the serum concentrations of Interleukin 18 (IL-18). **Time Frame:** 12 weeks **Description:** Venous blood will be collected before treatment and after 12 week . **Measure:** change in the serum concentrations of Nitric oxide (NO). **Time Frame:** 12 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients newly diagnosed with T2DM with diet control and good glycemic index ( Hb A1C\< 7 ) * Age range between 18 and 60 years old. * Both sexes. * Stage 1and Stage 2 CKD according to KDIGO . * Controlled HTN . Exclusion Criteria: * Pregnant and lactating females. * Patients with hypersensitivity to nicorandil. * Other Causes of CKD or Nephropathy eg : Uncontrolled HTN , Renal Malignancy , collagen disease as Amyloidosis and some autoimmune disease as ( SLE and Rh.fever ) . * Uncontrolled HTN and its antihypertensive medications ( ACEI , ARB ) and other antihypertensive medications . * Patients receiving nephrotoxic drugs as aminoglycosides, non-steroidal anti inflammatory drugs and contrast media. **Maximum Age:** 60 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Mohammed A El-hazzab **Phone:** 201151998914 **Role:** CONTACT #### Locations **Location 1:** **City:** Tanta **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Mohammed A El-hazzab - **Phone:** 201151998914 - **Role:** CONTACT **Country:** Egypt **Facility:** Tanta University **State:** EL Gharbia **Status:** RECRUITING ## Derived Section ### Condition Browse Module - Ancestors - ID: D000044882 - Term: Glucose Metabolism Disorders - ID: D000008659 - Term: Metabolic Diseases - ID: D000004700 - Term: Endocrine System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M7115 - Name: Diabetes Mellitus - Relevance: HIGH - As Found: Diabetes Mellitus - ID: M7119 - Name: Diabetes Mellitus, Type 2 - Relevance: HIGH - As Found: Type 2 Diabetes Mellitus - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown - ID: M25403 - Name: Glucose Metabolism Disorders - Relevance: LOW - As Found: Unknown - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003920 - Term: Diabetes Mellitus - ID: D000003924 - Term: Diabetes Mellitus, Type 2 ### Intervention Browse Module - Ancestors - ID: D000000889 - Term: Anti-Arrhythmia Agents - ID: D000000959 - Term: Antihypertensive Agents - ID: D000014665 - Term: Vasodilator Agents - ID: D000014803 - Term: Vitamin B Complex - ID: D000014815 - Term: Vitamins - ID: D000018977 - Term: Micronutrients - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: Hypo - Name: Hypoglycemic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Micro - Name: Micronutrients - Abbrev: AnArAg - Name: Anti-Arrhythmia Agents - Abbrev: AnAg - Name: Antihypertensive Agents - Abbrev: VaDiAg - Name: Vasodilator Agents - Abbrev: Hemat - Name: Hematinics - Abbrev: Vi - Name: Vitamins ### Intervention Browse Module - Browse Leaves - ID: M11667 - Name: Metformin - Relevance: LOW - As Found: Unknown - ID: M21946 - Name: Nicorandil - Relevance: HIGH - As Found: Anterior chamber - ID: M4213 - Name: Anti-Arrhythmia Agents - Relevance: LOW - As Found: Unknown - ID: M4277 - Name: Antihypertensive Agents - Relevance: LOW - As Found: Unknown - ID: M17412 - Name: Vasodilator Agents - Relevance: LOW - As Found: Unknown - ID: M17558 - Name: Vitamins - Relevance: LOW - As Found: Unknown - ID: M17546 - Name: Vitamin B Complex - Relevance: LOW - As Found: Unknown - ID: M8618 - Name: Folic Acid - Relevance: LOW - As Found: Unknown - ID: M21009 - Name: Micronutrients - Relevance: LOW - As Found: Unknown - ID: M16885 - Name: Trace Elements - Relevance: LOW - As Found: Unknown - ID: T446 - Name: Folic Acid - Relevance: LOW - As Found: Unknown - ID: T448 - Name: Folate - Relevance: LOW - As Found: Unknown - ID: T475 - Name: Vitamin B9 - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000020108 - Term: Nicorandil ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06430112 **Brief Title:** Liposomal Bupivacaine vs Ropivacaine for TAPBs **Official Title:** Liposomal Bupivacaine vs Ropivacaine for Ultrasound-guided Transversus Abdominis Plane Blocks in Laparoscopic Lower Abdominal Tumor Resection: A Prospective Randomized Trial #### Organization Study ID Info **ID:** B2023-485-01 #### Organization **Class:** OTHER **Full Name:** Sun Yat-sen University ### Status Module #### Completion Date **Date:** 2024-06 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-21 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-05-20 **Type:** ACTUAL #### Start Date **Date:** 2023-11-01 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Sun Yat-sen University #### Responsible Party **Investigator Affiliation:** Sun Yat-sen University **Investigator Full Name:** Ping Yu **Investigator Title:** Doctor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Is US Export:** False ### Description Module **Brief Summary:** Few studies have compared the efficacy of ultrasound (US)-guided TAP blocks with Liposomal bupivacaine(LB) versus ropivacaine in reducing postoperative opioid usage in patients undergoing laparoscopic lower abdominal tumor Resection. Therefore, we are conducting this prospective, randomized controlled trial to compare the postoperative analgesic effects of LB and ropivacaine for TAP blocks among patients undergoing laparoscopic colorectal procedures. **Detailed Description:** This study aimed to investigate the impact of liposomal bupivacaine (LB) on postoperative opioid usage for ultrasound(US)-guided transversus abdominis plane (TAP) blocks in laparoscopic colorectal resections. We divided 76 patients into two groups. An injection of bilateral TAP blocks was administered to LB group using 133mg liposomal bupivacaine in each block (266mg total), and to R group using 20 ml 0.25% ropivacaine in each block (40 ml total). Opioid consumption and pain scores at 6h, 24h, 48h and 72h were recorded postoperatively, as well as the total intraoperative remifentanil dose, the hospital stay lengths after surgery, and adverse events including dizziness, nausea, and vomiting. ### Conditions Module **Conditions:** - Abdominal Tumor - Postoperative Analgesia - Liposomal Bupivacaine - Ropivacaine **Keywords:** - liposomal bupivacaine - ropivacaine - transversus abdominis plane block - laparoscopic lower abdominal tumor resection - opioid consumption ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - PARTICIPANT **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 74 **Type:** ESTIMATED **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Liposomal Bupivacaine was used in the group **Intervention Names:** - Drug: Liposomal Bupivacaine **Label:** Liposomal Bupivacaine group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Ropivacaine was used in this group **Intervention Names:** - Drug: Ropivacaine **Label:** Ropivacaine group **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Liposomal Bupivacaine group **Description:** After induction of anesthesia, bilateral TAPB was performed under ultrasound guidance. The patients in the bupivacaine liposome group were injected with bupivacaine liposome 133mg(10ml+ 10ml 0.9% normal saline mixed into 20ml)/ point (two points in total). **Name:** Liposomal Bupivacaine **Other Names:** - Bupivacaine liposome **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Ropivacaine group **Description:** Patients in ropivacaine group were given 0.25% ropivacaine 20ml/ point (two points in total). **Name:** Ropivacaine **Other Names:** - Ropivacaine Hydrochloride Injection **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The amount of drug used in the postoperative analgesia pump **Measure:** Postoperative opioid use **Time Frame:** 3 days postoperatively #### Secondary Outcomes **Description:** Postoperative VAS score **Measure:** Postoperative pain score **Time Frame:** 3 days postoperatively **Description:** Postoperative adverse reactions were followed up **Measure:** Postoperative adverse reactions **Time Frame:** 3 days postoperatively ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Patients undergoing laparoscopic resection of lower abdominal tumors 2. ASA grade II-III 3. Age: 18-70 years. Exclusion Criteria: 1. (1) The patient does not agree to participate in the clinical study 2. (2) The patient has a clear history of opioid tolerance or allergy 3. (3) The patient has a history of local anesthetic allergy 4. (4) Previous history of dementia, mental illness or other central nervous system diseases 5. (5) Have a history of chronic pain or are taking opioids and other analgesics 6. (6) Patients are generally in poor condition with a history of serious diseases of cardiovascular system, respiratory system, digestive system, urinary system or central nervous system, and may not survive for more than 3 months 7. (7) The patient had any of the following conditions in the 12 months before surgery: myocardial infarction, severe/unstable angina pectoris, coronary artery bypass grafting, congestive heart failure, cerebrovascular accident, pulmonary embolism 8. (8) Pregnant women 9. (9) Unable to cooperate with follow-up or poor compliance 10. (10) Patients with acute myocardial infarction, cardiac arrest or shock during surgery or hospitalization 11. (11) ASA score above grade III. **Maximum Age:** 70 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Ping Yu **Phone:** 00-86-13631373286 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Jingdun Xie **Phone:** 00-86-13560380116 **Role:** CONTACT #### Locations **Location 1:** **City:** Guangzhou **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Jingdun Xie - **Phone:** +8613560380116 - **Role:** CONTACT **Country:** China **Facility:** Jingdun Xie **State:** Guangdong **Status:** RECRUITING **Zip:** 510060 #### Overall Officials **Official 1:** **Affiliation:** Department of Anesthesiology,Sun Yat-Sen University Cancer Center **Name:** Jingdun Xie **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Access Criteria:** The persons who were willing to study. **Description:** https://www.medicalresearch.org.cn/,Time: After completing the academic paper for publication **Info Types:** - STUDY_PROTOCOL **IPD Sharing:** YES **Time Frame:** After completing the academic paper for publication ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M7 - Name: Abdominal Neoplasms - Relevance: HIGH - As Found: Abdominal Tumors ### Condition Browse Module - Meshes - ID: D000000008 - Term: Abdominal Neoplasms ### Intervention Browse Module - Ancestors - ID: D000000779 - Term: Anesthetics, Local - ID: D000000777 - Term: Anesthetics - ID: D000002492 - Term: Central Nervous System Depressants - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000018689 - Term: Sensory System Agents - ID: D000018373 - Term: Peripheral Nervous System Agents ### Intervention Browse Module - Browse Branches - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Analg - Name: Analgesics ### Intervention Browse Module - Browse Leaves - ID: M4107 - Name: Anesthetics - Relevance: LOW - As Found: Unknown - ID: M5315 - Name: Bupivacaine - Relevance: HIGH - As Found: Following - ID: M1700 - Name: Ropivacaine - Relevance: HIGH - As Found: Current - ID: M4033 - Name: Analgesics, Opioid - Relevance: LOW - As Found: Unknown - ID: M4109 - Name: Anesthetics, Local - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000002045 - Term: Bupivacaine - ID: D000077212 - Term: Ropivacaine ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06430099 **Brief Title:** Rate of Blood Pressure Control Among Hypertensive Patients With Hemodialysis in Sohag University Hospital **Official Title:** Rate of Blood Pressure Control Among Hypertensive Patients With Hemodialysis in Sohag University Hospital #### Organization Study ID Info **ID:** Sohagu. #### Organization **Class:** OTHER **Full Name:** Sohag University ### Status Module #### Completion Date **Date:** 2024-12-20 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-31 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-29 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2024-12-20 **Type:** ESTIMATED #### Start Date **Date:** 2024-05-24 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Hager Abdo Mohamed #### Responsible Party **Investigator Affiliation:** Sohag University **Investigator Full Name:** Hager Abdo Mohamed **Investigator Title:** Principal Investigator **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** The goal of this Cross-sectional study is to detect hypertensive patients with hemodialysis in Sohag University Hospital and controlled patients and noncontrolled patients. The main questions it aims to answer are: 1. What is the pattern of blood pressure control among patients receiving hemodialysis? 2. What are factors associated with successful blood pressure control? 3. What is the level of patient knowledge and awareness regarding blood pressure management? 4. What are the challenges and barriers faced by patients in achieving optimal blood pressure control? Participants Blood pressure calculated by taking the average of three consecutive days measurement. **Detailed Description:** 1. Survey Type: Cross-sectional study. 2. Target Population: Patients undergoing hemodialysis. 3. Sample Size: The target sample size are all hypertensive patients in Sohag university hospital dialysis unit 4. Survey Method: person to person interview in dialysis units will be used for data collection. Blood pressure calculated by taking the average of three consecutive days * 1st day (Dialysis Day): - Blood pressure will be measured (pre dialysis, inter dialysis, post dialysis). * 2nd day (Inter Dialytic Day): - Blood pressure will be measured two times (AM, PM). * 3rd day (Dialysis Day): - Blood pressure will be measured (pre dialysis, inter dialysis, post dialysis). ### Conditions Module **Conditions:** - Hemodialysis - Hypertension **Keywords:** - hypertension hemodialysis ### Design Module #### Design Info **Observational Model:** CASE_ONLY **Time Perspective:** CROSS_SECTIONAL #### Enrollment Info **Count:** 200 **Type:** ESTIMATED **Patient Registry:** True **Study Type:** OBSERVATIONAL **Target Duration:** 3 Days ### Outcomes Module #### Primary Outcomes **Measure:** Rate of blood pressure control among hypertensive patients with hemodialysis in Sohag University Hospital with hemodialysis in Sohag University Hospital **Time Frame:** 3 days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: - Participants must be * 18 years or older. * currently receiving hemodialysis. * Hypertensive patients. Exclusion Criteria: * patients under 18 years old. * Patients stopped hemodialysis. * Patients with ESRD not receiving hemodialysis. **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** hypertensive patients with hemodialysis in Sohag University Hospital ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Hager A Mohamed, M.B.B.CH **Role:** CONTACT #### Locations **Location 1:** **City:** Sohag **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Hager A Mohamed, M.B.B.CH - **Role:** CONTACT ***Contact 2:*** - **Name:** Hager A Mohamed, M.B.B.CH - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Egypt **Facility:** Faculty of Medicine Sohag University **Zip:** 82524 #### Overall Officials **Official 1:** **Affiliation:** Sohag University **Name:** Hassan A Hassanien, professor **Role:** STUDY_CHAIR **Official 2:** **Affiliation:** Sohag University **Name:** Alaa A Ghaleb, professor **Role:** STUDY_CHAIR **Official 3:** **Affiliation:** Sohag University **Name:** Ahmed N Nour Eldin, Lecturer **Role:** STUDY_CHAIR ### References Module #### References **Citation:** Susel J, Batycka-Baran A, Reich A, Szepietowski JC. Uraemic pruritus markedly affects the quality of life and depressive symptoms in haemodialysis patients with end-stage renal disease. Acta Derm Venereol. 2014 May;94(3):276-81. doi: 10.2340/00015555-1749. **PMID:** 24217858 **Citation:** Lopes AA, Bragg J, Young E, Goodkin D, Mapes D, Combe C, Piera L, Held P, Gillespie B, Port FK; Dialysis Outcomes and Practice Patterns Study (DOPPS). Depression as a predictor of mortality and hospitalization among hemodialysis patients in the United States and Europe. Kidney Int. 2002 Jul;62(1):199-207. doi: 10.1046/j.1523-1755.2002.00411.x. **PMID:** 12081579 **Citation:** Joshi VD. Quality of life in end stage renal disease patients. World J Nephrol. 2014 Nov 6;3(4):308-16. doi: 10.5527/wjn.v3.i4.308. **PMID:** 25374827 **Citation:** Garcia-Llana H, Remor E, Selgas R. Adherence to treatment, emotional state and quality of life in patients with end-stage renal disease undergoing dialysis. Psicothema. 2013 Feb;25(1):79-86. doi: 10.7334/psicothema2012.96. **PMID:** 23336548 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M10024 - Name: Hypertension - Relevance: HIGH - As Found: Hypertension - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006973 - Term: Hypertension ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06430086 **Brief Title:** Mechanistic Effect of Walnut Consumption on Sleep Quality **Official Title:** Mechanistic Effect of Walnut Consumption on Sleep Quality #### Organization Study ID Info **ID:** AAAV1362 #### Organization **Class:** OTHER **Full Name:** Columbia University #### Secondary ID Infos **Domain:** USDA/NIFA **ID:** GRANT13949102 **Type:** OTHER_GRANT ### Status Module #### Completion Date **Date:** 2026-12-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-06-04 **Type:** ACTUAL **Last Update Submit Date:** 2024-06-03 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2026-12-31 **Type:** ESTIMATED #### Start Date **Date:** 2024-06-01 **Type:** ESTIMATED **Status Verified Date:** 2024-06 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Collaborators **Class:** FED **Name:** United States Department of Agriculture (USDA) **Class:** OTHER **Name:** California Walnut Commission #### Lead Sponsor **Class:** OTHER **Name:** Columbia University #### Responsible Party **Investigator Affiliation:** Columbia University **Investigator Full Name:** Marie-Pierre St-Onge **Investigator Title:** Associate Professor of Nutritional Medicine **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Poor sleep quality is very common in modern society. Walnuts contain many nutrients that may be helpful for sleep, including melatonin and polyphenols. Some studies show that eating foods high in melatonin and polyphenols improves sleep quality, but walnuts have not been studied specifically. This study proposes to test if eating walnuts improves sleep compared to a food that lacks these sleep-promoting factors. The investigators expect that walnut consumption for 4 days will increase melatonin levels and lead to better sleep quality compared to a high-carbohydrate, high-sugar food. The study will enroll middle-aged and older adults with sleep complaints to participate in this study. Each person will eat the two different foods for 4 days each in random order. The 4-day periods will be separated by at least 2-3 weeks. Sleep quality will be measured by questionnaire and with a wrist monitor every day. The investigators will also do a sleep study using electroencephalography (EEG) on night 3 and take measures of circadian physiology (natural body rhythms) in the laboratory on day 4 (including overnight) by measuring body temperature and blood and urine melatonin. The study findings may provide new options to improve sleep health from increased walnut consumption. **Detailed Description:** Walnuts are a nutrient-rich food which provides melatonin and polyphenols. While there is evidence that dietary intakes of foods high in melatonin and polyphenols positively influence sleep quality, the effect of walnuts has not been investigated. The investigators propose to fill this knowledge gap by testing the effects of walnut consumption on serum melatonin and resulting sleep and circadian biology. The study hypotheses are that walnut consumption for 4 days will increase melatonin levels, suggestive of more robust circadian rhythms, and lead to better sleep quality compared to a high-carbohydrate high-sugar (HCHS) equivalent. Using a randomized controlled crossover trial, the study aims to: 1) determine the effect of walnut vs HCHS consumption on melatonin levels; and 2) determine the effect of walnut vs HCHS consumption on sleep and circadian physiology. Adult males and females with poor sleep quality will consume three servings/day of walnuts or an equicaloric HCHS food for 4 days. Sleep quality will be measured nightly using the Karolinska Sleep Diary and wrist actigraphy; sleep architecture from polysomnography will be measured on night 3. Circadian physiology will be assessed on day 4 using body temperature and hourly serum melatonin and on the morning of day 5 from overnight urinary 6-sulfatoxymelatonin. Given the extent of poor sleep, our findings may open new avenues to improve sleep health from increased walnut consumption. ### Conditions Module **Conditions:** - Poor Sleep Quality **Keywords:** - Randomized crossover study - Controlled feeding - Dietary intervention - Inpatient visit - Outpatient monitoring ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER **Intervention Model Description:** Randomized crossover design ##### Masking Info **Masking:** SINGLE **Masking Description:** Statistician will be masked to study condition. Participants cannot be masked. Other personnel involved in the study cannot be masked. **Who Masked:** - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 24 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants will consume 3 servings/day of walnuts (3 oz/d) over 4 days and have a washout for 2-3 weeks then crossover to consume 3 equicaloric servings of a HCHS food over 4 days. Over each 4-day period, participants will sleep and eat at home for the first 3 days and will be admitted to the Inpatient Clinical Research Resource of the Irving Institute for Clinical and Translational Research of CUIMC on day 4 for in-depth profiling circadian physiology. Participants will be discharged on the morning of day 5. **Intervention Names:** - Other: Walnut consumption - Other: HCHS consumption **Label:** Walnut - washout - HCHS **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Participants will consume 3 equicaloric servings of a HCHS food over 4 days and have a washout for 2-3 weeks then crossover to consume 3 servings/day of walnuts (3 oz/d) for 4 days. Over each 4-day period, participants will sleep and eat at home for the first 3 days and will be admitted to the Inpatient Clinical Research Resource of the Irving Institute for Clinical and Translational Research of CUIMC on day 4 for in-depth profiling circadian physiology. Participants will be discharged on the morning of day 5. **Intervention Names:** - Other: Walnut consumption - Other: HCHS consumption **Label:** HCHS - washout - Walnut **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - HCHS - washout - Walnut - Walnut - washout - HCHS **Description:** Participants will add one serving (1 oz) of walnuts at their self-defined breakfast, lunch, and dinner for 4 days. The study will provide study foods at 3 main meals each day to evaluate a temporal effect of the food on melatonin concentrations throughout the day. **Name:** Walnut consumption **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - HCHS - washout - Walnut - Walnut - washout - HCHS **Description:** Participants will add one HCHS food (one PopTarts® pastry) to each of their 3 main meals of the day for 4 days. The study will provide study foods at 3 main meals each day to evaluate a temporal effect of the food on melatonin concentrations throughout the day. An energy-matched high-carbohydrate, high-sugar (HCHS) alternative, representative of a common US snack food, on sleep quality in adults with habitually poor sleep quality. **Name:** HCHS consumption **Type:** OTHER ### Outcomes Module #### Other Outcomes **Description:** This is to measure Endothelial cell inflammation in endothelial cells collected from a forearm vein. Repeated for each phase. Fasted sample. **Measure:** NFkB level **Time Frame:** Day 4 (or Day 5) #### Primary Outcomes **Description:** Serum melatonin will be measured via last testing of blood samples collected on day 4, in an inpatient setting. Repeated for each phase. **Measure:** Serum melatonin **Time Frame:** Baseline (9AM; Hour 0), Hour 1, Hour 2, Hour 3, Hour 4, Hour 5, Hour 6, Hour 7, Hour 8, Hour 9, Hour 10, Hour 11, Hour 12, Hour 13, Hour 14, Hour 15 (Midnight) **Description:** Sleep quality will be assessed daily using wrist actigraphy. Variables include sleep fragmentation index and sleep efficiency. Repeated for each phase. **Measure:** Sleep quality index **Time Frame:** Night 1, Night 2, Night 3, Night 4 **Description:** Slow wave sleep will be measured using electroencephalography, in the participant's home. Repeated for each phase. **Measure:** Slow wave sleep index **Time Frame:** Night 3 #### Secondary Outcomes **Description:** This is to measure Melatonin production in urine samples. Repeated for each phase. **Measure:** 6-sulfatoxymelatonin level **Time Frame:** Night 4 to morning of Day 5 (Approximately up to 12 hours) **Description:** Proximal to distal body temperature gradient measured using thermochron devices (iButtons). Repeated for each phase. In patient. Over 24 hours. **Measure:** Body temperature **Time Frame:** Day 4 **Description:** Self-reported sleep quality assessed using the Karolinska Sleep Diary (higher score represents better sleep). Repeated for each phase. **Measure:** Sleep quality score **Time Frame:** Days 2, 3, 4, 5 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Equal numbers of men and women (12 male and 12 post-menopausal female) * Equal number of individuals with normal weight (18.5-24.9 kg/m2) and overweight (25-29.9 kg/m2) * Participants will self-report poor sleep quality, reflected by a global score \>5 on Pittsburgh Sleep Quality Index Exclusion Criteria: * Diagnosed sleep disorder * Participants with conditions that could affect sleep will be excluded: * smoking, excessive caffeine intake (\>300 mg/day) * shift work * chronic pain * diagnosis of a chronic disease (e.g., uncontrolled hypertension, pre-diabetes, type 2 diabetes, chronic kidney disease, chronic obstructive pulmonary disease), * autoimmune diseases * cardiovascular event or cancer in the past 24 months * psychiatric/neurologic disease or disorder, or sleep disorder (diagnosed or high risk for sleep apnea, chronic insomnia, restless leg syndrome, narcolepsy) * use of medications that influence CYP1A2 enzymes * Allergy/intolerance to nuts, tree nuts, or unwilling to eat study foods **Healthy Volunteers:** True **Maximum Age:** 65 Years **Minimum Age:** 45 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Lena Navarro, BS **Phone:** 347-963-8845 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Claudia Dreyer, BS **Phone:** 347-881-6008 **Role:** CONTACT #### Locations **Location 1:** **City:** New York **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Lena Navarro, BS - **Phone:** 347-963-8845 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Claudia Dreyer, BS - **Phone:** 347-881-6008 - **Role:** CONTACT ***Contact 3:*** - **Name:** Marie-Pierre St-Onge, PhD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** Columbia University Irving Medical Center **State:** New York **Zip:** 10032 #### Overall Officials **Official 1:** **Affiliation:** Associate Professor of Nutritional Medicine **Name:** Marie-Pierre St-Onge, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Description:** Data will be submitted to Zenodo, a generalist repository that is participating in the NIH Generalist Repository Ecosystem Initiative. We will submit metadata associated with the datasets to Zenodo. The repository will provide metadata, persistent identifiers, and long-term access for open and controlled access. Each study created in Zenodo is assigned a digital object identifier (DOI). This data DOI will be referenced in the publication to allow the research community easy access to the exact data used in the publication. To request access of the data, researchers will use the standard processes at Zenodo. Given that we seek the widest possible availability, in most cases all that is necessary is obtaining a Zenodo account from the repository web site. **Info Types:** - STUDY_PROTOCOL - SAP - ICF - CSR - ANALYTIC_CODE **IPD Sharing:** YES **Time Frame:** Within 12 months of final study completion. **URL:** https://about.zenodo.org/policies/ ## Derived Section ### Intervention Browse Module - Browse Branches - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Ot - Name: Other Dietary Supplements - Abbrev: HB - Name: Herbal and Botanical ### Intervention Browse Module - Browse Leaves - ID: M11533 - Name: Melatonin - Relevance: LOW - As Found: Unknown - ID: T410 - Name: Melatonin - Relevance: LOW - As Found: Unknown - ID: T143 - Name: English Walnut - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06430073 **Acronym:** INFRAGEN **Brief Title:** Effect of Infections and Global DNA Methylation on Frailty Trajectories in Hospitalized Older Patients (INFRAGEN) **Official Title:** Effect of Infections and Global DNA Methylation on Frailty Trajectories in Hospitalized Older Patients: a Multicenter Observational Study (INFRAGEN) #### Organization Study ID Info **ID:** 83/2023/Oss/AOUFe #### Organization **Class:** OTHER **Full Name:** University Hospital of Ferrara ### Status Module #### Completion Date **Date:** 2026-03-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-22 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2025-09-01 **Type:** ESTIMATED #### Start Date **Date:** 2024-05-20 **Type:** ESTIMATED **Status Verified Date:** 2024-03 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-03-26 **Study First Submit QC Date:** 2024-05-22 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Azienda Ospedaliera di Padova **Class:** OTHER **Name:** Fondazione IRCCS San Gerardo dei Tintori **Class:** OTHER **Name:** Azienda Ospedaliera Universitaria Policlinico #### Lead Sponsor **Class:** OTHER **Name:** University Hospital of Ferrara #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** This prospective multicenter study aims at exploring the impact of infections on intra-hospital and 3-month changes in the frailty profile of older inpatients. To understand the complex pathways under the relationship between infections and frailty, this study will evaluate infection-related clinical and biochemical markers of systemic inflammation and genetics/epigenetics markers at ward admission. The interplay between clinical, functional, and genetics/epigenetics factors will be evaluated in a subgroup of patients by testing whether 3-month changes in frailty concur with changes in the genomic DNA markers. This study will help characterize the pathophysiological mechanisms of frailty and identify at-risk conditions that may accelerate its course. **Detailed Description:** Infectious diseases are among the most common causes of hospitalization in older adults. Indeed, recent data report that more than 15% of hospital admissions in adults 65 years or older are due to infections, mainly in the urinary and respiratory tracts. Frailty is a well-known geriatric syndrome characterized by reduced individual resilience and increased vulnerability to external stressors. The prevalence of frailty ranges from around 10% in the community setting to almost 50% among institutionalized individuals. Although both infectious diseases and frailty are associated with negative outcomes for the health of older adults and the healthcare system, their interplay has not been largely explored. In particular, it is not clear whether and to which extent acute infectious diseases might affect frailty, fastening its development or hampering its reversion. The overall goal of the proposed project is to evaluate the impact of acute infections on frailty trajectories in older hospitalized patients from the pre-admission status to 3 months after hospital discharge. Moreover, a comprehensive set of sociodemographic, clinical, functional, and genetic/epigenetic factors will be assessed as possible effect modifiers in the association between infections and frailty trajectories. This multicenter prospective observational study includes four geriatric wards (Ferrara, Padova, Milano, and Napoli) and involves individuals with no or mild-to-moderate frailty. A novel and interesting aspect will be represented by the analysis of genetic and epigenetic factors, i.e. global DNA methylation and telomere length. This point will make possible exploring the complex pathophysiologic mechanisms of frailty development using a translational approach involving both basic science and clinical researchers. Overall, this study will help better identify at-risk conditions that may accelerate the course of frailty. Therefore, the project findings may promote the importance of interventions that could counteract frailty development during the hospital stay and should be addressed primarily to the categories of patients at highest risk. ### Conditions Module **Conditions:** - Aging - Frailty - Telomere Shortening - Inflammation - Hospital Infection ### Design Module #### Bio Spec **Description:** Blood sample **Retention:** SAMPLES_WITH_DNA #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 340 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The study cohort will be composed of 340 older patients hospitalized in a Geriatric Unit with no or mild frailty in the pre-admission period, and who will present acute infections at admission or during the hospital stay. **Label:** Total sample ### Outcomes Module #### Primary Outcomes **Description:** Frailty will be valuated through the Frailty Index (i.e. score from 0 to 1, with higher values corresponding to higher frailty), considering clinical and functional data. Pre-admission frailty will be retrospectively assessed to reflect the participant's status in the two weeks prior to the hospital admission. Frailty assessment will be repeated within 48h before the hospital discharge. **Measure:** Change in frailty index from pre-admission to hospital discharge **Time Frame:** From 14 days before admission to hospital discharge (up to 60 days) #### Secondary Outcomes **Description:** Frailty will be evaluated through the Clinical Frailty Scale (i.e. score from 1 to 9, with higher values corresponding to higher frailty). Pre-admission frailty will be retrospectively assessed to reflect the participant's status in the two weeks prior to the hospital admission. Frailty assessment will be repeated within 48h before the hospital discharge. **Measure:** Change in Clinical Frailty Scale from pre-admission to hospital discharge **Time Frame:** From 14 days before admission to hospital discharge (up to 60 days) **Description:** All-cause mortality will be computed for participants with vs without infections associated with a systemic inflammatory response. **Measure:** Difference in in-hospital mortality between inpatients with vs without infections with systemic inflammation **Time Frame:** From 14 days before admission to hospital discharge (up to 60 days) **Description:** The length of hospital stay (number of days from hospital admission to hospital discharge) will be computed for participants with vs without infections associated with a systemic inflammatory response. **Measure:** Difference in the length of hospital stay between inpatients with vs without infections with systemic inflammation **Time Frame:** From 14 days before admission to hospital discharge (up to 60 days) **Description:** DNA extraction from whole blood will be performed by Automated Genomic DNA Purification EZ1 XL machine (QIAGEN). Global DNA methylation assessment will be performed by "highly quantitative pyrosequencing" technique as genome-wide DNA methylation levels and as gene promoter associated CpG islands utilizing selected age-related methylation marker loci and at LINE-1 repetitive elements (as a surrogate for genome-wide methylation). The patterns of global DNA methylation will be assessed in duplicate for each sample and expressed in percentage as the mean obtained by the two evaluations and considered valuable with a discrepancy \<2%. Methylation percentages can be stratified into quartiles, and the middle two quartiles combined will be used as the reference category. The frequencies of individuals belonging to the highest and lowest DNA methylation quartiles will be compared between individuals reporting worsening in FI or CFS during the hospitalization vs those stable in frailty levels. **Measure:** Difference in the global DNA methylation between individuals with stable vs worsened frailty during the hospital stay. **Time Frame:** From 14 days before admission to hospital discharge (up to 60 days) **Description:** Telomere length will be compared between individuals with stable vs worsened frailty during the hospital stay. DNA extraction from whole blood will be performed by Automated Genomic DNA Purification EZ1 XL machine (QIAGEN). Leukocyte Telomere Length (LTL) will be assessed by quantitative PCR as previously described as predictors of biological age in frailty and mortality association studies. As a measure of the relative Telomere length, the ratio of the telomere repeat copy number to the number of single-copy gene ratio (T/S ratio) will be determined by quantitative PCR using the single-copy gene 36B4 for reference and a standard curve. Quality controls and assay validation tests will be assessed by official commercial recognized standards (Qiagen, LifeTechnology). **Measure:** Difference in telomere length between individuals with stable vs worsened frailty during the hospital stay **Time Frame:** From 14 days before admission to hospital discharge (up to 60 days) **Description:** Frailty will be valuated through the Frailty Index (i.e. score from 0 to 1, with higher values corresponding to higher frailty), considering clinical and functional data. Frailty assessment will be performed within 48h before the hospital discharge and after 3-month from the hospital discharge. **Measure:** Change in frailty index from hospital discharge to 3-month follow-up **Time Frame:** From hospital discharge until 3 months after hospital discharge (time frame: 3 months) **Description:** Frailty will be evaluated through the Clinical Frailty Scale (i.e. score from 1 to 9, with higher values corresponding to higher frailty). Frailty assessment will be performed within 48h before the hospital discharge and after 3-month from the hospital discharge. **Measure:** Change in Clinical Frailty Scale from hospital discharge to 3-month follow-up **Time Frame:** From hospital discharge until 3 months after hospital discharge (time frame: 3 months) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * confirmed diagnosis of acute infection diseases at hospital admission or during the hospital stay, according to specific ICD-9 codes with or without systemic inflammatory reaction; * pre-admission non-frailty or mild frailty assessed using the Clinical Frailty Scale (CFS \< 6). Exclusion Criteria: * terminally ill patients with an estimated life expectancy less than 3 months; * presence of pre-admission frailty (CFS ≥ 6); * unwillingness to participate in the study or to complete the follow-up assessments **Minimum Age:** 70 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - OLDER_ADULT **Study Population:** The project will involve older patients hospitalized in the Geriatric Units of the University Hospital of Ferrara, Padua, Monza, and Napoli. All patients non-frail or with mild frailty in the pre-admission period, and who will present a confirmed diagnosis of acute infection diseases at hospital admission or during the hospital stay, will be enrolled in the study. ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Caterina Trevisan, PhD **Phone:** +393896743650 **Role:** CONTACT #### Overall Officials **Official 1:** **Affiliation:** Università degli Studi di Ferrara **Name:** Stefano Volpato, MD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Franceschi C, Campisi J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci. 2014 Jun;69 Suppl 1:S4-9. doi: 10.1093/gerona/glu057. **PMID:** 24833586 **Citation:** Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA; Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001 Mar;56(3):M146-56. doi: 10.1093/gerona/56.3.m146. **PMID:** 11253156 **Citation:** Greco GI, Noale M, Trevisan C, Zatti G, Dalla Pozza M, Lazzarin M, Haxhiaj L, Ramon R, Imoscopi A, Bellon S, Maggi S, Sergi G. Increase in Frailty in Nursing Home Survivors of Coronavirus Disease 2019: Comparison With Noninfected Residents. J Am Med Dir Assoc. 2021 May;22(5):943-947.e3. doi: 10.1016/j.jamda.2021.02.019. Epub 2021 Feb 22. **PMID:** 33757725 **Citation:** Huoman J, Sayyab S, Apostolou E, Karlsson L, Porcile L, Rizwan M, Sharma S, Das J, Rosen A, Lerm M. Epigenetic rewiring of pathways related to odour perception in immune cells exposed to SARS-CoV-2 in vivo and in vitro. Epigenetics. 2022 Dec;17(13):1875-1891. doi: 10.1080/15592294.2022.2089471. Epub 2022 Jun 26. **PMID:** 35758003 **Citation:** Iwai-Saito K, Shobugawa Y, Aida J, Kondo K. Frailty is associated with susceptibility and severity of pneumonia in older adults (A JAGES multilevel cross-sectional study). Sci Rep. 2021 Apr 12;11(1):7966. doi: 10.1038/s41598-021-86854-3. **PMID:** 33846416 **Citation:** Lapham K, Kvale MN, Lin J, Connell S, Croen LA, Dispensa BP, Fang L, Hesselson S, Hoffmann TJ, Iribarren C, Jorgenson E, Kushi LH, Ludwig D, Matsuguchi T, McGuire WB, Miles S, Quesenberry CP Jr, Rowell S, Sadler M, Sakoda LC, Smethurst D, Somkin CP, Van Den Eeden SK, Walter L, Whitmer RA, Kwok PY, Risch N, Schaefer C, Blackburn EH. Automated Assay of Telomere Length Measurement and Informatics for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort. Genetics. 2015 Aug;200(4):1061-72. doi: 10.1534/genetics.115.178624. Epub 2015 Jun 19. **PMID:** 26092717 **Citation:** Park CM, Kim W, Rhim HC, Lee ES, Kim JH, Cho KH, Kim DH. Frailty and hospitalization-associated disability after pneumonia: A prospective cohort study. BMC Geriatr. 2021 Feb 5;21(1):111. doi: 10.1186/s12877-021-02049-5. **PMID:** 33546614 **Citation:** Prampart S, Le Gentil S, Bureau ML, Macchi C, Leroux C, Chapelet G, de Decker L, Rouaud A, Boureau AS. Functional decline, long term symptoms and course of frailty at 3-months follow-up in COVID-19 older survivors, a prospective observational cohort study. BMC Geriatr. 2022 Jun 30;22(1):542. doi: 10.1186/s12877-022-03197-y. **PMID:** 35768781 **Citation:** Rockwood K, Mitnitski A. Frailty in relation to the accumulation of deficits. J Gerontol A Biol Sci Med Sci. 2007 Jul;62(7):722-7. doi: 10.1093/gerona/62.7.722. **PMID:** 17634318 **Citation:** Schneider CV, Schneider KM, Teumer A, Rudolph KL, Hartmann D, Rader DJ, Strnad P. Association of Telomere Length With Risk of Disease and Mortality. JAMA Intern Med. 2022 Mar 1;182(3):291-300. doi: 10.1001/jamainternmed.2021.7804. **PMID:** 35040871 **Citation:** Schork NJ, Beaulieu-Jones B, Liang W, Smalley S, Goetz LH. Does Modulation of an Epigenetic Clock Define a Geroprotector? Adv Geriatr Med Res. 2022;4(1):e220002. doi: 10.20900/agmr20220002. Epub 2022 Mar 29. **PMID:** 35466328 **Citation:** Seligman BJ, Berry SD, Lipsitz LA, Travison TG, Kiel DP. Epigenetic Age Acceleration and Change in Frailty in MOBILIZE Boston. J Gerontol A Biol Sci Med Sci. 2022 Sep 1;77(9):1760-1765. doi: 10.1093/gerona/glac019. **PMID:** 35037036 **Citation:** Vetter VM, Kalies CH, Sommerer Y, Spira D, Drewelies J, Regitz-Zagrosek V, Bertram L, Gerstorf D, Demuth I. Relationship Between 5 Epigenetic Clocks, Telomere Length, and Functional Capacity Assessed in Older Adults: Cross-Sectional and Longitudinal Analyses. J Gerontol A Biol Sci Med Sci. 2022 Sep 1;77(9):1724-1733. doi: 10.1093/gerona/glab381. **PMID:** 35032170 **Citation:** Vlachogiannis NI, Baker KF, Georgiopoulos G, Lazaridis C, van der Loeff IS, Hanrath AT, Sopova K, Tual-Chalot S, Gatsiou A, Spyridopoulos I, Stamatelopoulos K, Duncan CJA, Stellos K. Clinical frailty, and not features of acute infection, is associated with late mortality in COVID-19: a retrospective cohort study. J Cachexia Sarcopenia Muscle. 2022 Jun;13(3):1502-1513. doi: 10.1002/jcsm.12966. Epub 2022 Mar 7. **PMID:** 35257497 **Citation:** Wang J, Maxwell CA, Yu F. Biological Processes and Biomarkers Related to Frailty in Older Adults: A State-of-the-Science Literature Review. Biol Res Nurs. 2019 Jan;21(1):80-106. doi: 10.1177/1099800418798047. Epub 2018 Sep 9. **PMID:** 30198309 **Citation:** Yoshikawa TT, Norman DC. Geriatric Infectious Diseases: Current Concepts on Diagnosis and Management. J Am Geriatr Soc. 2017 Mar;65(3):631-641. doi: 10.1111/jgs.14731. Epub 2017 Jan 31. **PMID:** 28140454 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes - ID: D000007049 - Term: Iatrogenic Disease ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC01 - Name: Infections - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10293 - Name: Inflammation - Relevance: HIGH - As Found: Inflammation - ID: M1175 - Name: Frailty - Relevance: HIGH - As Found: Frailty - ID: M10283 - Name: Infections - Relevance: HIGH - As Found: Infection - ID: M6368 - Name: Communicable Diseases - Relevance: HIGH - As Found: Infection - ID: M6642 - Name: Cross Infection - Relevance: HIGH - As Found: Hospital Infection - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown - ID: M10099 - Name: Iatrogenic Disease - Relevance: LOW - As Found: Unknown - ID: T4202 - Name: Oculocerebral Syndrome With Hypopigmentation - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007239 - Term: Infections - ID: D000003141 - Term: Communicable Diseases - ID: D000003428 - Term: Cross Infection - ID: D000007249 - Term: Inflammation - ID: D000073496 - Term: Frailty ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06430060 **Brief Title:** The Clinical Investigation of Colgate Dual Zinc Toothpaste as Compared to Colgate Cavity Protection Toothpaste in Controlling Established Plaque and Gingivitis **Official Title:** The Clinical Investigation of Colgate Dual Zinc Toothpaste as Compared to Colgate Cavity Protection Toothpaste in Controlling Established Plaque and Gingivitis (A Threemonth Clinical Study) #### Organization Study ID Info **ID:** CRO-2024-03-GIN-DZN-CN-YPZ #### Organization **Class:** INDUSTRY **Full Name:** Colgate Palmolive ### Status Module #### Completion Date **Date:** 2024-08 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-24 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2024-08 **Type:** ESTIMATED #### Start Date **Date:** 2024-05 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-24 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Colgate Palmolive #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Qualified subjects will be enrolled and randomized to either one of the two study groups described above based on their initial Plaque and Gingivitis scores. Subjects will be instructed to use the products according to the instructions provided. Subjects will return to the dental office for evaluation after three months of product use. All subjects will be followed for adverse events throughout the study. ### Conditions Module **Conditions:** - Plaque, Dental - Gingivitis ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 90 **Type:** ESTIMATED **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** toothpaste **Intervention Names:** - Drug: zinc containing toothpaste **Label:** Colgate Dual Zinc Toothpaste **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** toothpaste **Intervention Names:** - Drug: MFP Fluoride toothpaste **Label:** Colgate Cavity Protection Toothpaste **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Colgate Dual Zinc Toothpaste **Description:** Toothpaste **Name:** zinc containing toothpaste **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Colgate Cavity Protection Toothpaste **Description:** toothpaste **Name:** MFP Fluoride toothpaste **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** A Loe-Silness Gingival Index score from 0 to 3 will be assigned by the examining dentist to all scoreable surfaces of the maxillary and mandibular teeth using a dental light and dental mirror. A whole mouth mean score for each subject will be determined by adding the values given by the examining dentist to each scoreable surface and dividing that number by the total number of surfaces scored. **Measure:** Loe-Silness Gingival Index score **Time Frame:** baseline, 2 week, 6 week, 3 month **Description:** A Quigley-Hein Plaque Index score of 0 to 5 will be assigned to all scoreable disclosed surfaces of the maxillary and mandibular teeth using a dental light and dental mirror. A whole mouth score for each subject will be determined by adding the values given by the dental examiner to each scoreable surface and dividing that number by the total number of surfaces scored. **Measure:** Quigley-Hein Plaque Index score **Time Frame:** baseline, 2 week, 6 week, 3 month ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Subjects, ages 18-70, inclusive. * Availability for the three-month duration of the clinical research study. * Good general health. * Minimum of 20 uncrowned permanent natural teeth (excluding third molars). * Initial gingivitis index of at least 1.0 as determined by the use of the Loe and Silness Gingival Index. * Initial plaque index of at least 1.5 as determined by the use of the Quigley and Hein Plaque Index (Turesky Modification). * Signed Informed Consent Form Exclusion Criteria: * Presence of orthodontic bands. * Presence of partial removable dentures. * Tumor(s) of the soft or hard tissues of the oral cavity. * Advanced periodontal disease (purulent exudate, tooth mobility, and/or extensive loss of periodontal attachment or alveolar bone). * Five or more carious lesions requiring immediate restorative treatment. * Antibiotic use any time during the one month prior to entry into the study. * Participation in any other clinical study or test panel within the one month prior to entry into the study. * Dental prophylaxis during the past two weeks prior to baseline examinations. * History of allergies to oral care/personal care consumer products or their ingredients. * On any prescription medicines that might interfere with the study outcome. * An existing medical condition which prohibits eating or drinking for periods up to 4 hours. * History of alcohol or drug abuse. * Pregnant or lactating subjects **Healthy Volunteers:** True **Maximum Age:** 70 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Deyu Hu, DDS, MS **Phone:** 86-1390-803-4990 **Role:** CONTACT #### Locations **Location 1:** **City:** Chengdu **Country:** China **Facility:** West China Dental Institute of Chengdu **State:** Sichuan **Zip:** 610041 #### Overall Officials **Official 1:** **Affiliation:** West China Dental Institute of Chengdu **Name:** Deyu Hu, DDS, MS **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007239 - Term: Infections - ID: D000005882 - Term: Gingival Diseases - ID: D000010510 - Term: Periodontal Diseases - ID: D000009059 - Term: Mouth Diseases - ID: D000009057 - Term: Stomatognathic Diseases - ID: D000003741 - Term: Dental Deposits - ID: D000014076 - Term: Tooth Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: BC07 - Name: Mouth and Tooth Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M9003 - Name: Gingivitis - Relevance: HIGH - As Found: Gingivitis - ID: M6970 - Name: Dental Plaque - Relevance: HIGH - As Found: Plaque, Dental - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M8994 - Name: Gingival Diseases - Relevance: LOW - As Found: Unknown - ID: M13419 - Name: Periodontal Diseases - Relevance: LOW - As Found: Unknown - ID: M12019 - Name: Mouth Diseases - Relevance: LOW - As Found: Unknown - ID: M12017 - Name: Stomatognathic Diseases - Relevance: LOW - As Found: Unknown - ID: M6938 - Name: Dental Deposits - Relevance: LOW - As Found: Unknown - ID: M16831 - Name: Tooth Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000005891 - Term: Gingivitis - ID: D000003773 - Term: Dental Plaque ### Intervention Browse Module - Ancestors - ID: D000002327 - Term: Cariostatic Agents - ID: D000020011 - Term: Protective Agents - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: Micro - Name: Micronutrients ### Intervention Browse Module - Browse Leaves - ID: M8587 - Name: Fluorides - Relevance: HIGH - As Found: Components - ID: M140080 - Name: Listerine - Relevance: LOW - As Found: Unknown - ID: M15771 - Name: Sodium Fluoride - Relevance: LOW - As Found: Unknown - ID: M17768 - Name: Zinc - Relevance: LOW - As Found: Unknown - ID: M21869 - Name: Protective Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000005459 - Term: Fluorides ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06430047 **Brief Title:** Efficacy and Safety of EsoDuo® **Official Title:** The Role of an EsoDuo® to Control Reflux Symptoms Related to the Acid; a Multicenter, Open-labeled, Phase 4 Study [RACER Study] #### Organization Study ID Info **ID:** B73_02GERD2107 #### Organization **Class:** INDUSTRY **Full Name:** Chong Kun Dang Pharmaceutical ### Status Module #### Completion Date **Date:** 2025-05 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-21 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2025-01 **Type:** ESTIMATED #### Start Date **Date:** 2022-11-25 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Chong Kun Dang Pharmaceutical #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Clinical Trial to Evaluate the Effects of EsoDuo® in Controlling Reflux Symptoms Related to the Acid **Detailed Description:** The Role of an EsoDuo® to Control Reflux Symptoms Related to the Acid; a Multicenter, Open-labeled, Phase 4 Study \[RACER Study\] ### Conditions Module **Conditions:** - Gastro Esophageal Reflux ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 180 **Type:** ESTIMATED **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Drug: EsoDuo® Tablet **Label:** Experimental Group **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Experimental Group **Description:** QD, PO **Name:** EsoDuo® Tablet **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** the symptoms of GERD : heartburn or acid reflux **Measure:** The time taken to control the symptoms of GERD **Time Frame:** 2 weeks after the clinical trial participation ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Male or Female aged ≥ 19 years 2. Patients diagnosed with non-erosive reflux disease or mild erosive reflux disease 3. Episode of heartburn the GERD symptom(either heartburn or gastric acid reflux) Exclusion Criteria: 1. Surgery history on stomach or esophagus 2. Barrett's esophagus (over 3cm), esophageal varices, esophageal stricture, esophageal achalasia, eosinophilic esophagitis, and primary motility disorders 3. Patients diagnosed with Grade C or Grade D according to the LA Classification system during upper gastrointestinal endoscopy 4. Patients with a history of malignancy within the past 5 years prior to the screening visit (Visit 1) 5. Patients who have taken prohibited concomitant medications within 14 days prior to the screening visit or require continuous administration of prohibited medications during the trial period. 6. Clinically significant Abnormal Lab test 7. Pregnant woman, Breastfeeding woman. **Minimum Age:** 19 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Hwoon-Yong Jung, M.D, PhD **Phone:** 82+2-3010-3197 **Role:** CONTACT #### Locations **Location 1:** **City:** Seoul **Contacts:** ***Contact 1:*** - **Name:** Hwoon-Yong Jung, PhD - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Phone:** 82+2-3010-3197 - **Role:** CONTACT **Country:** Korea, Republic of **Facility:** Asan Medical Center **Status:** RECRUITING #### Overall Officials **Official 1:** **Affiliation:** Asan Medical Cental of Korea **Name:** Hwoon-Yong Jung, M.D, PhD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000015154 - Term: Esophageal Motility Disorders - ID: D000003680 - Term: Deglutition Disorders - ID: D000004935 - Term: Esophageal Diseases - ID: D000005767 - Term: Gastrointestinal Diseases - ID: D000004066 - Term: Digestive System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC09 - Name: Ear, Nose, and Throat Diseases ### Condition Browse Module - Browse Leaves - ID: M8880 - Name: Gastroesophageal Reflux - Relevance: HIGH - As Found: Gastro Esophageal Reflux - ID: M17874 - Name: Esophageal Motility Disorders - Relevance: LOW - As Found: Unknown - ID: M17875 - Name: Esophageal Spasm, Diffuse - Relevance: LOW - As Found: Unknown - ID: M6882 - Name: Deglutition Disorders - Relevance: LOW - As Found: Unknown - ID: M8085 - Name: Esophageal Diseases - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000005764 - Term: Gastroesophageal Reflux ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06430034 **Brief Title:** Contributions of 3D Photography and Stereophotogrammetry to the Evaluation of Facial Symmetrization by Botulinum Toxin Injections. Study of Facial Symmetry Before and After Botulinum Toxin Injections on the Face of Patients Suffering From Sequellar Peripheral Facial Paralysis **Official Title:** Contributions of 3D Photography and Stereophotogrammetry to the Evaluation of Facial Symmetrization Through Botulinum Toxin Injections, in Patients With Peripheral Facial Palsy #### Organization Study ID Info **ID:** 24IUFC01 #### Organization **Class:** OTHER **Full Name:** Centre Hospitalier Universitaire de Nice ### Status Module #### Completion Date **Date:** 2025-11-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-06-05 **Type:** ACTUAL **Last Update Submit Date:** 2024-06-04 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2025-11-01 **Type:** ESTIMATED #### Start Date **Date:** 2023-11-01 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-24 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Centre Hospitalier Universitaire de Nice #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** "This is a prospective, single-center study. The main objective of our study will be to objectively evaluate the improvement of facial symmetry after botulinum toxin injection on the face in patients suffering from sequelae of peripheral facial paralysis. A secondary objective will be to assess the utility of 3D photography and stereophotogrammetry to detect and quantify facial changes relevant to this type of treatment. The number of patients included in the study is expected to be 15 at minimum. Our study will rely on 3D photographs taken with the Vectra H2 Imaging System camera device (Canfield Scientific, Inc., Fairfield, New Jersey), which will be captured before and 3 weeks to 1 month after botulinum toxin injection into the facial muscles. Various analyses of static and dynamic symmetry will be performed using the Vectra software: bi-pupillary line angle / bi-commissural line angle, superposition of healthy and pathological sides followed by RMS (root mean square) calculation, analysis of pre- and post-injection skin displacement vectors. The results of these analyses will allow conclusions to be drawn regarding the objective efficacy of botulinum toxin injections for facial symmetrization in patients with peripheral facial paralysis, as well as to adapt injection patterns based on the severity of facial paralysis." ### Conditions Module **Conditions:** - Peripheral Facial Palsy ### Design Module #### Design Info **Observational Model:** CASE_ONLY **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 20 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Outcomes Module #### Primary Outcomes **Description:** Assessment of static and dynamic symmetry: bi-pupillary line / bi-commissural line angle - measure in degrees **Measure:** Objective assessment of facial symmetrization after botulinum toxin injection - line **Time Frame:** Day of injection and 3-4 weeks after. **Description:** Assessment of static and dynamic symmetry: superposition of healthy and pathological sides and calculation of RMS (root mean square) **Measure:** Objective assessment of facial symmetrization after botulinum toxin injection **Time Frame:** Day of injection and 3-4 weeks after. **Description:** Assessment of static and dynamic symmetry: analysis of pre- and post-injection skin displacement vectors, Before and after botulinum toxin injection. **Measure:** Objective assessment of facial symmetrization after botulinum toxin injection **Time Frame:** Day of injection and 3-4 weeks after. #### Secondary Outcomes **Description:** Measure of symmetrization : degrees of facial palsy. **Measure:** Evaluation of the importance of symmetrization based on injection patterns, types, and degrees of facial palsy. **Time Frame:** Day of injection and 3-4 weeks after. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: -Patients who received injections of botulinum toxin in the facial muscles, aimed at facial symmetrization at Head and Neck Institute, Nice, France at Head and Neck Institute, Nice, France. Exclusion Criteria: * History of corrective surgery for facial palsy, significant facial surgery, neurodegenerative diseases, the presence of skin imperfections or facial tumors that would impede a rigorous analysis of wrinkles and facial movements. **Maximum Age:** 100 Years **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Patients who received injections of botulinum toxin in the facial muscles, aimed at facial symmetrization at Head and Neck Institute, Nice, France ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Robin PRADEL **Phone:** 0673398497 **Phone Ext:** +33 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Charles SAVOLDELLI, MD **Phone:** 0648275014 **Phone Ext:** +33 **Role:** CONTACT #### Locations **Location 1:** **City:** Nice **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Robin PRADEL - **Phone:** 0673398497 - **Phone Ext:** +33 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Charles SAVOLDELLI, MD - **Phone:** 0648275014 - **Phone Ext:** +33 - **Role:** CONTACT **Country:** France **Facility:** CHU NICE **State:** Alpes Maritimes **Status:** RECRUITING **Zip:** 0600 #### Overall Officials **Official 1:** **Affiliation:** Centre Hospitalier Universitaire de Nice **Name:** Charles SAVOLDELLI **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes - ID: D000009059 - Term: Mouth Diseases - ID: D000009057 - Term: Stomatognathic Diseases - ID: D000010243 - Term: Paralysis - ID: D000009461 - Term: Neurologic Manifestations - ID: D000009422 - Term: Nervous System Diseases - ID: D000006566 - Term: Herpesviridae Infections - ID: D000004266 - Term: DNA Virus Infections - ID: D000014777 - Term: Virus Diseases - ID: D000007239 - Term: Infections - ID: D000005155 - Term: Facial Nerve Diseases - ID: D000003389 - Term: Cranial Nerve Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC01 - Name: Infections - Abbrev: BC07 - Name: Mouth and Tooth Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M13157 - Name: Paralysis - Relevance: LOW - As Found: Unknown - ID: M22138 - Name: Bell Palsy - Relevance: HIGH - As Found: Facial Palsy - ID: M8301 - Name: Facial Paralysis - Relevance: HIGH - As Found: Facial Palsy - ID: M21089 - Name: Facies - Relevance: HIGH - As Found: Facial - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown - ID: M12019 - Name: Mouth Diseases - Relevance: LOW - As Found: Unknown - ID: M12017 - Name: Stomatognathic Diseases - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M9643 - Name: Herpesviridae Infections - Relevance: LOW - As Found: Unknown - ID: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M7442 - Name: DNA Virus Infections - Relevance: LOW - As Found: Unknown - ID: M8298 - Name: Facial Nerve Diseases - Relevance: LOW - As Found: Unknown - ID: M6605 - Name: Cranial Nerve Diseases - Relevance: LOW - As Found: Unknown - ID: T707 - Name: Bell's Palsy - Relevance: HIGH - As Found: Facial Palsy ### Condition Browse Module - Meshes - ID: D000020330 - Term: Bell Palsy - ID: D000005158 - Term: Facial Paralysis - ID: D000019066 - Term: Facies ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M5183 - Name: Botulinum Toxins - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06430021 **Acronym:** PRO-NEM1 **Brief Title:** Study of the Value of hPG80 (Circulating Progastrin) for the Diagnosis of Neuroendocrine Tumours in Patients With an MEN1 Mutation **Official Title:** Study of the Value of hPG80 (Circulating Progastrin) for the Diagnosis of Neuroendocrine Tumours in Patients With an NEM1 Mutation: the Progastrin-NEM1 Study #### Organization Study ID Info **ID:** GOUDET BIODENA 2023 #### Organization **Class:** OTHER **Full Name:** Centre Hospitalier Universitaire Dijon ### Status Module #### Completion Date **Date:** 2025-06 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-21 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2025-06 **Type:** ESTIMATED #### Start Date **Date:** 2024-06 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Centre Hospitalier Universitaire Dijon #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant disease with a high degree of penetrance (\>80% of patients). It is caused by the presence of the MEN1 mutation located on chromosome 11q13. The prevalence of this mutation is estimated at approximately 1/30,000. This hereditary syndrome is characterized by the presence of tumours of the endocrine system (adenoma of the parathyroid, pituitary and adrenal glands, neuroendocrine tumors - NETs - of the endocrine pancreas, duodenum, lung or thymus), which threaten the health of these patients. Other malignant tumors such as breast cancer are also more common in patients with MEN1. The clinical manifestations of MEN1 are linked to the location of the adenomas and NETs and their secretory products. Indeed, most NETs produce and secrete numerous peptide hormones (in the case of Insulinomas, Gastrinomas, VIPomas, Glucagonomas or PPomas for example). This causes a specific clinical syndrome, which can be detected in the blood serum. However, most NETs are "non-functional" tumors, which do not have specific secretions. Among general tumor markers, chromogranin A (CgA) is widely used as a biomarker for monitoring NETs. CgA is a secretory protein released into the blood by neuroendocrine cells. However, the performance of CgA as a diagnostic biomarker is too limited to be used for the early identification of NETs, particularly in patients with MEN1. This is why patients with MEN1 undergo regular biological and morphological examinations, at least once a year, to screen for the development of adenomas and NETs. However, CgA or hormone secretions assays, and imaging examinations (MRI, CT scan, or duodenopancratic endoscopic ultrasound (EUS)) are tedious and stressful for patients; in addition, they all have their limitations (poor performance for biological tests; irradiation for CT scan; need for anesthesia for endoscopic ultrasound, etc.). Consequently, there is a need for new markers to identify NETs in this population as early as possible. Progastrin is a pro-hormone that, under physiological conditions, is matured into gastrin in the G cells of the antrum of the stomach. The role of gastrin is to stimulate gastric acid secretion during digestion. It also plays an important role in regulating cell growth in the gastric mucosa. In pathological situations, it has been shown that the GAST gene, which codes for progastrin, is over-expressed in human tumor cells of different origins, leading to the accumulation of progastrin within them. Tumor cells that are unable to mature progastrin into gastrin, either because the maturation enzymes are not expressed or are inhibited, will secrete it. This circulating progastrin is then called hPG80 (to differentiate it from intracellular progastrin) and is detectable in patient blood. hPG80 is a new biomarker for the detection of different types of cancer. It appears to be elevated in the early stages of the disease, potentially more so than other biomarkers such as circulating tumor DNA (ctDNA) or NETest. In addition, hPG80 is easily measured in plasma using the DxPG80.Lab ELISA (Progastrin Manufacturing). The analytical characteristics of this CE-marked in vitro diagnostic test have been published in the Analytical Methods journal. It has been validated in numerous studies of various cancers, including NET patients. In addition, a study conducted by the team at Progastrin Manufacturing (formerly ECS-Progastrin) showed that hPG80 was unequivocally present in the peripheral blood of patients with 11 different types of cancer, with a concentration significantly higher than that found in blood donors considered to be healthy. We therefore hypothesize that hPG80 could also be a biomarker for NETs in MEN1. ### Conditions Module **Conditions:** - Neuroendocrine Tumors - MEN1 Mutation ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 297 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** patients with proven MEN1, symptomatic or not **Intervention Names:** - Biological: blood sample **Label:** patient ### Interventions #### Intervention 1 **Arm Group Labels:** - patient **Description:** 8 mL blood sample in EDTA tube **Name:** blood sample **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Description:** Significant NET = metastatic or progressive morphologically or supracentimetric NET of the pancreas, duodenum, lung/bronchus or thymus absence of significant NET = patient with sub-centimetric, stable and asymptomatic NET / with or without adenoma **Measure:** Presence of at least one significant NET vs. absence of significant NET or resected NET without relapse confirmed by thoracic-abdominal imaging **Time Frame:** Within 3 months before or after inclusion. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients with proven MEN1, symptomatic or not, confirmed on the basis of the following international criteria (Thakker et al.): * patients with an MEN1 mutation; * patients belonging to an identified MEN1 family in which at least one first-degree relative has been affected and has at least one MEN1-related lesion; * patients without a positive genetic test or a family history of the disease, but with at least two of the three main MEN1 lesions (parathyroid adenomas, duodenopancreatic NETs and pituitary tumours). * Patients aged between 18 and 60 years, * Patients who have undergone thoracoabdominal imaging (MRI, and/or CT and/or somatostatin receptor imaging (PET or octreotide scan)) within 3 months prior to inclusion or are due to undergo imaging within 3 months of inclusion to document the presence of NETs, * Regardless of the treatment they are receiving (treatment naïve or treated patient), * Regardless of the type of disease associated with MEN1 (presence or absence of NET, adenoma....), * Patients who did not object to taking part in the study. Exclusion Criteria: * Person not affiliated to national health insurance * Person subject to a measure legal protection (curatorship, guardianship) or a court order * Pregnant, parturient or breastfeeding mothers **Maximum Age:** 60 Years **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT **Study Population:** Patients will be seen for follow-up consultations ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Côme LEPAGE **Phone:** 0380293750 **Phone Ext:** +33 **Role:** CONTACT #### Locations **Location 1:** **City:** Dijon **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Côme LEPAGE - **Phone:** 0380293750 - **Phone Ext:** +33 - **Role:** CONTACT **Country:** France **Facility:** Chu Dijon Bourgogne **Zip:** 21000 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000017599 - Term: Neuroectodermal Tumors - ID: D000009373 - Term: Neoplasms, Germ Cell and Embryonal - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000009380 - Term: Neoplasms, Nerve Tissue ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M20495 - Name: Neuroendocrine Tumors - Relevance: HIGH - As Found: Neuroendocrine Tumors - ID: M19845 - Name: Neuroectodermal Tumors - Relevance: LOW - As Found: Unknown - ID: M20388 - Name: Neuroectodermal Tumors, Primitive - Relevance: LOW - As Found: Unknown - ID: M12318 - Name: Neoplasms, Germ Cell and Embryonal - Relevance: LOW - As Found: Unknown - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M12325 - Name: Neoplasms, Nerve Tissue - Relevance: LOW - As Found: Unknown - ID: T4091 - Name: Neuroendocrine Tumor - Relevance: HIGH - As Found: Neuroendocrine Tumors - ID: T4092 - Name: Neuroepithelioma - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000018358 - Term: Neuroendocrine Tumors ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06430008 **Brief Title:** The Relationship Between Total Sialic Acid and Superoxide Dismutase and the Diagnosis and Prognosis of Lipoid Pneumonia **Official Title:** A Study to Explore the Correlation Between Total Sialic Acid Combined With Superoxide Dismutase and the Diagnosis and Prognosis of Lipoid Pneumonia #### Organization Study ID Info **ID:** 2024-KY-144 #### Organization **Class:** OTHER **Full Name:** China-Japan Friendship Hospital ### Status Module #### Completion Date **Date:** 2024-12-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-21 **Overall Status:** ENROLLING_BY_INVITATION #### Primary Completion Date **Date:** 2024-10-01 **Type:** ESTIMATED #### Start Date **Date:** 2024-05-01 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Hu Yinan #### Responsible Party **Investigator Affiliation:** China-Japan Friendship Hospital **Investigator Full Name:** Hu Yinan **Investigator Title:** China-Japan Friendship Hospital **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** The goal of this observational study is to explore the correlation between total sialic acid combined with superoxide dismutase and the diagnosis and prognosis of lipid pneumonia in the patient with lipid pneumonia, cough, bacterial and fungal pneumonia, cryptogenic organizing pneumonia, pulmonary alveolar proteinosis, lung mucinous adenocarcinoma and pulmonary edema. The main question it aims to answer is: Whether superoxide dismutase (SOD) and total sialic acid (TSA) could be used as diagnostic markers to distinguish lipid pneumonia from patient with cough, and bacterial and fungal pneumonia, cryptogenic organizing pneumonia, pulmonary alveolar proteinosis, lung mucinous adenocarcinoma and pulmonary edema, whether SOD and TSA be associated with the prognosis of patients with lipid pneumonia? Participants will answer online survey questions about their symptoms, changes in oxygen status, and changes in the most recent CT image of the lung for up to 10 years after treatment. We will count participants' baseline data including: gender, age, smoking history, comorbidities, lung function, imaging findings, hormone use or not, ICU treatment, death or not, the type of cause of lipid pneumonia, how it is diagnosed, and their baseline SOD and TSA. ### Conditions Module **Conditions:** - Lipid Pneumonia - Superoxide Dismutase - Sialic Acid ### Design Module #### Design Info **Observational Model:** CASE_CONTROL **Time Perspective:** RETROSPECTIVE #### Enrollment Info **Count:** 160 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Label:** lipid pneumonia #### Arm Group 2 **Label:** cough #### Arm Group 3 **Label:** cryptogenic organizing pneumonia #### Arm Group 4 **Label:** pulmonary alveolar proteinosis #### Arm Group 5 **Label:** bacterial pneumonia #### Arm Group 6 **Label:** fungal pneumonia #### Arm Group 7 **Label:** pulmonary edema #### Arm Group 8 **Label:** mucinous adenocarcinoma of the lung ### Outcomes Module #### Primary Outcomes **Measure:** superoxide dismutase **Time Frame:** At the time of admission #### Secondary Outcomes **Measure:** sialic acid **Time Frame:** At the time of admission **Measure:** death or not **Time Frame:** Within 10 years after discharge **Measure:** neutrophil-to-lymphocyte ratio **Time Frame:** At the time of admission ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Age≥ 18 years old; 2. The diagnosis of lipoid pneumonia must be supported by lung biopsy pathological support or positive oil red O or Sudan staining in bronchoalveolar lavage fluid; 3. Patients with bacterial and fungal pneumonia must be supported by etiological evidence; 4. Patients with cryptogenic organizing pneumonia and pulmonary alveolar proteinosis must be supported by lung biopsy pathology; 5. Patients with lung mucinous adenocarcinoma must be supported by lung tissue biopsy; 6. Lung imaging of patients with pulmonary edema must show paving stone signs; Exclusion Criteria: 1. Age\&lt; 18 years old; 2. The patient only has a history of lipid inhalation and no pathology or positive lipoid staining; 3. Co-infection with the corona virus disease 2019 at the onset of illness; 4. Pregnant **Minimum Age:** 18 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** This study includes the lipoid pneumonia patients, patients with cough in the upper respiratory tract only, patients with bacterial and fungal pneumonia, patients with cryptogenic organizing pneumonia and pulmonary alveolar proteinosis, patients with lung mucinous adenocarcinoma and patients with pulmonary edema. ### Contacts Locations Module #### Locations **Location 1:** **City:** Beijing **Country:** China **Facility:** China-Japan Friendship Hospital **State:** Beijing **Zip:** 100000 #### Overall Officials **Official 1:** **Affiliation:** China-Japan Friendship Hospital **Name:** Yinan Hu **Role:** STUDY_CHAIR ### IPD Sharing Statement Module **Description:** All IPD collected throughout the trial, only IPD used in the results publication **Info Types:** - STUDY_PROTOCOL - SAP - ICF - CSR - ANALYTIC_CODE **IPD Sharing:** YES **URL:** http://www.medresman.org.cn ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012141 - Term: Respiratory Tract Infections - ID: D000007239 - Term: Infections - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases - ID: D000011015 - Term: Pneumonia, Aspiration ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M13904 - Name: Pneumonia - Relevance: HIGH - As Found: Pneumonia - ID: M13907 - Name: Pneumonia, Lipid - Relevance: HIGH - As Found: Lipoid Pneumonia - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M14978 - Name: Respiratory Tract Infections - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: M13905 - Name: Pneumonia, Aspiration - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000011014 - Term: Pneumonia - ID: D000011017 - Term: Pneumonia, Lipid ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M16264 - Name: Superoxide Dismutase - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429995 **Acronym:** SFPMAMMA **Brief Title:** Standard Follow-up Program (SFP) for Breast Cancer Patients **Official Title:** Standard Follow-up Program (SFP) for Breast Cancer Patients #### Organization Study ID Info **ID:** SFP MAMMA #### Organization **Class:** OTHER **Full Name:** University Medical Center Groningen ### Status Module #### Completion Date **Date:** 2030-01-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-22 **Overall Status:** ENROLLING_BY_INVITATION #### Primary Completion Date **Date:** 2030-01-01 **Type:** ESTIMATED #### Start Date **Date:** 2008-01-01 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2023-09-22 **Study First Submit QC Date:** 2024-05-22 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University Medical Center Groningen #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Motive: In order to improve the treatment technique, a comprehensive follow-up program is needed to obtain all relevant patient, treatment and toxicity data from breast cancer patients. Goal:to set-up and maintain a database containing treatment results in terms of tumor control, side effects, complications and patient-reported quality of life. A standard database of patiënts receiving photon treatment will be created. These data are then linked to dose-volume data of radiotherapy, with the aim to build prediction models for both tumor control and toxicity after radio (chemo) therapy that can later be used for selecting patients for proton treatment. To set-up and maintain a database containing treatment results in terms of tumor control, side effects, complications and patient-reported quality of life. A standard database of patients receiving photon treatment will be created. These data are then linked to dose-volume data of radiotherapy, with the aim to build prediction models for both tumor control and toxicity after radio (chemo) therapy that can later be used for selecting patients for proton treatment. ### Conditions Module **Conditions:** - Breast Cancer **Keywords:** - Acute toxicity - Late toxicity - Prediction models ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 10000 **Type:** ESTIMATED **Patient Registry:** True **Study Type:** OBSERVATIONAL **Target Duration:** 30 Years ### Arms Interventions Module ### Interventions #### Intervention 1 **Name:** Radiotherapy **Other Names:** - chemoradiation **Type:** RADIATION ### Outcomes Module #### Other Outcomes **Description:** Hb level (mmol/l) measured in blood **Measure:** Hemoglobin (Hb) **Time Frame:** Before start of radiation therapy **Description:** Ht levels (L/L) measured in blood **Measure:** Hematocrit (Ht) **Time Frame:** Before start of radiation therapy **Description:** Leukocytes + differential count (10E9/l) measured in blood **Measure:** Leukocytes **Time Frame:** Before start of radiation therapy **Description:** Creatinine levels (mmol/l) measured in blood **Measure:** Creatinine **Time Frame:** Before start of radiation therapy **Description:** eGFR calculated from creatinine levels (ml/min) **Measure:** Estimated Glomerular filtration rate (eGFR) **Time Frame:** Before start of radiation therapy **Description:** Urea levels (mmol/l) measured in blood **Measure:** Urea **Time Frame:** Before start of radiation therapy **Description:** HbA1c levels (mmol/mol) measured in blood **Measure:** Hemoglobin A1c (HbA1c) **Time Frame:** Before start of radiation therapy **Description:** Cholesterol levels (mmol/L) measured in blood **Measure:** Cholesterol **Time Frame:** Before start of radiation therapy **Description:** HDL cholesterol levels (mmol/L) measured in blood **Measure:** High-densitiy-lipoprotein cholesterol (HDL cholesterol) **Time Frame:** Before start of radiation therapy **Description:** LDL cholesterol levels (mmol/L) measured in blood **Measure:** Low-density-lipoprotein cholesterol (LDL cholesterol) **Time Frame:** Before start of radiation therapy **Description:** Triglycerides levels (mmol/L) measured in blood **Measure:** Triglycerides **Time Frame:** Before start of radiation therapy **Description:** HsCRP levels (mg/L) measured in blood **Measure:** High sensitive C-reactive protein (hsCRP) **Time Frame:** Before start of radiation therapy **Description:** TSH levels (mU/L) measured in blood **Measure:** Thyroid stimulating hormone (TSH) **Time Frame:** Before start of radiation therapy, 1 and 2 years after radiation therapy **Description:** FT4 levels (pmol/L) measured in blood **Measure:** Free Thyroxine-4 (FT4) **Time Frame:** Before start of radiation therapy, 1 and 2 years after radiation therapy **Description:** Patient-rated demographics measured with the baseline questionnaire on Demographics (unvalidated questionnaire) **Measure:** Patient-rated Demographics measured with the baseline questionnaire on Demographics **Time Frame:** Before start of radiation therapy **Description:** Patient-rated symptoms are measured with the Quality of Life Questionnaire-BR23 (EORTC QLQ-BR23) **Measure:** Patient-rated symptoms measured with the EORTC QLQ-BR23 **Time Frame:** Before start of radiation therapy, at 2 weeks after last day of radiation therapy, and at 3,6,12 months after last day of radiation therapy and thereafter yearly, anticipated average 20 years **Description:** Patient-rated symptoms are measured with the Breast Cancer Questionnaire (BCSCQ: Based on the BCTOS (1) and the questionnaire on Patients' satisfaction with the cosmetic outcome by Sneeuw at al.(2)) **Measure:** Patient-rated symptoms measured with the BCSCQ **Time Frame:** Before start of radiation therapy, at 2 weeks after last day of radiation therapy, and at 3,6,12 months after last day of radiation therapy and thereafter yearly, anticipated average 20 years. **Description:** Patient-rated symptoms are measured with the baseline questionnaire on Cardiovascular Diseases and Risk Factors and Lung Diseases before start of radiation therapy (unvalidated questionnaire) **Measure:** Patient-rated symptoms measured with the questionnaire on Cardiovascular Diseases and Risk Factors and Lung Diseases (baseline) **Time Frame:** Before start of radiation therapy **Description:** Patient-rated symptoms are measured with the follow up questionnaire on Cardiovascular Diseases and Risk Factors and Lung Diseases (semi)annually after last day of radiation therapy (unvalidated questionnaire) **Measure:** Patient-rated symptoms with the questionnaire on Cardiovascular Diseases and Risk Factors and Lung Diseases (follow up) **Time Frame:** 6 and 12 months after last day of radiation therapy and thereafter yearly, anticipated average 20 years **Description:** Patient-rated symptoms are measured with the questionnaire on Performance Status (unvalidated questionnaire) **Measure:** Patient-rated symptoms measured with the questionnaire on Performance Status **Time Frame:** Before start of radiation therapy, at 2 weeks after last day of radiation therapy, and at 3,6,12 months after last day of radiation therapy and thereafter yearly, anticipated average 20 years **Description:** Patient-rated symptoms are measured with the questionnaire on Locoregional Tumor Control/New Primary Tumor (unvalidated questionnaire) **Measure:** : Patient-rated symptoms measured with the questionnaire on Locoregional Tumor Control/New Primary Tumor **Time Frame:** 6 and 12 months after last day of radiation therapy and thereafter yearly, anticipated average 20 years **Description:** Patient-rated quality of life is measured with the Quality-of-Life Questionnaire-C30 (EORTC QLQ-C30) **Measure:** Patient-rated Quality of Life measured with the EORTC QLQ-C30 **Time Frame:** Before start of radiation therapy, at 2 weeks after last day of radiation therapy, and at 3,6,12 months after last day of radiation therapy and thereafter yearly, anticipated average 20 years **Description:** Patient-rated quality of life is measured with the EuroQol Health questionnaire 5-level version (EuroQoL-5D_5L) **Measure:** Patient-rated Quality of Life measured with the EuroQoL-5D_5L **Time Frame:** Before start of radiation therapy, at 2 weeks after last day of radiation therapy, and at 3,6,12 months after last day of radiation therapy and thereafter yearly, anticipated average 20 years **Description:** Patient-rated quality of life is measured with the Quality of Life Questionnaire-BR23 (EORTC QLQ-BR23). **Measure:** Patient-rated Quality of Life measured with EORTC QLQ-BR23 **Time Frame:** Before start of radiation therapy, at 2 weeks after last day of radiation therapy, and at 3,6,12 months after last day of radiation therapy and thereafter yearly, anticipated average 20 years #### Primary Outcomes **Description:** Acute Toxicity is measured with Common Terminology Criteria for Adverse Events (CTCAE). **Measure:** Score of Acute toxicity **Time Frame:** Before start of radiation therapy and during radiation therapy and at 2 weeks after last day of radiation therapy. **Description:** Late Toxicity is measured with Common Terminology Criteria for Adverse Events (CTCAE). **Measure:** Score of Late toxicity **Time Frame:** At one and two years after last day of radiation therapy. #### Secondary Outcomes **Description:** Overall survival **Measure:** Overall survival **Time Frame:** At 2 weeks after last day of radiation therapy and thereafter yearly, anticipated average 5-10 years. **Description:** Loco-regional tumor control **Measure:** Loco-regional tumor control **Time Frame:** At 2 weeks after last day of radiation therapy and thereafter yearly, anticipated average 5-10 years. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients with breast cancer Patients receiving a radiotherapy dose Exclusion Criteria: * Failure to comply with any of the inclusion criteria **Gender Based:** True **Maximum Age:** 99 Years **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Patients with breast cancer receiving radiotherapy ### Contacts Locations Module #### Locations **Location 1:** **City:** Groningen **Country:** Netherlands **Facility:** University Medical Center Groningen **Zip:** 9700RB #### Overall Officials **Official 1:** **Affiliation:** UMCG **Name:** Anne Crijns, MD, PhD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Stanton AL, Krishnan L, Collins CA. Form or function? Part 1. Subjective cosmetic and functional correlates of quality of life in women treated with breast-conserving surgical procedures and radiotherapy. Cancer. 2001 Jun 15;91(12):2273-81. **PMID:** 11413515 **Citation:** Sneeuw KC, Aaronson NK, Yarnold JR, Broderick M, Regan J, Ross G, Goddard A. Cosmetic and functional outcomes of breast conserving treatment for early stage breast cancer. 1. Comparison of patients' ratings, observers' ratings, and objective assessments. Radiother Oncol. 1992 Nov;25(3):153-9. doi: 10.1016/0167-8140(92)90261-r. **PMID:** 1470691 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000001941 - Term: Breast Diseases - ID: D000012871 - Term: Skin Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M5220 - Name: Breast Neoplasms - Relevance: HIGH - As Found: Breast Cancer - ID: M5218 - Name: Breast Diseases - Relevance: LOW - As Found: Unknown - ID: M15674 - Name: Skin Diseases - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001943 - Term: Breast Neoplasms ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429982 **Brief Title:** Dexamethasone Use in Pediatric Rhabdomyolysis Patients in Addition to Standard Protocols **Official Title:** A Clinical Trial to Assess Whether Dexamethasone Addition to Standard Protocols for Non-Traumatic Rhabdomyolysis of Unknown or Genetic Etiologies Improves Patient Outcomes #### Organization Study ID Info **ID:** STUDY00000710 #### Organization **Class:** OTHER **Full Name:** Children's National Research Institute ### Status Module #### Completion Date **Date:** 2026-12-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-23 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2025-12-01 **Type:** ESTIMATED #### Start Date **Date:** 2024-10-01 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2023-08-31 **Study First Submit QC Date:** 2024-05-23 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Children's National Research Institute #### Responsible Party **Investigator Affiliation:** Children's National Research Institute **Investigator Full Name:** Natasha Shur **Investigator Title:** MD, Principal Investigator, Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Oversight Has DMC:** True ### Description Module **Brief Summary:** There is a significant unmet need for optimized treatment in rhabdomyolysis. There are few prospective interventional studies on treatment for rhabdomyolysis, a condition which affects diverse and underrepresented populations at a higher rate. While steroids are often used off-label, a systematic study has not yet been initiated, and steroids have not been yet considered in as a consideration to standard care guidelines. The hypothesis is that patients who receive dexamethasone in addition to standard care versus placebo and standard care will have improvement in pain, length of hospital stay, and decrease in kidney complications. **Detailed Description:** Study Objective: This is a single center, 2-year, blinded prospective randomized study for those diagnosed with rhabdomyolysis age six months-25 years using dexamethasone versus placebo treatment in addition to standard care in up to 50 patients. Study Design: Patients will be enrolled with a 2:1 ratio of treatment of dexamethasone for 5 days versus placebo treatment for 5 days in addition to receiving standard care. The treatment period for each subject will be five days treatment with oral treatment once per day with study drug (dexamethasone versus placebo). All patients will also receive standard care. Patients and their parent/ caregiver will have the option to complete surveys before and after treatment in order to assess pain level and treatment improvement. Chart review will be performed on all patients throughout and after the five-day study treatment period. There will be no additional interventions. ### Conditions Module **Conditions:** - Rhabdomyolysis ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** There will be a 2: 1 treatment ratio of dexamethasone treated group versus placebo. ##### Masking Info **Masking:** QUADRUPLE **Masking Description:** This study will be double-blinded. The pharmacy will determine which patients are in the study group. **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 50 **Type:** ESTIMATED **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Dexamethasone five days with 0.6 mg/ kg dose per day max 16 mg dose. Standard care will also be provided. **Intervention Names:** - Drug: Dexamethasone **Label:** Dexamethasone group **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Placebo for five days with one dose per day placebo oral dosing. Standard care will also be provided. **Intervention Names:** - Drug: Placebo **Label:** Placebo group **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Dexamethasone group **Description:** Steroid five day treatment **Name:** Dexamethasone **Other Names:** - DexPak **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo group **Description:** Placebo control group **Name:** Placebo **Other Names:** - Sugar Pill **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Number of days Length of Stay in Each Group **Measure:** Length of Stay **Time Frame:** Primarily 5 days - 1 year **Description:** Creatinine Kinase trend comparison between groups **Measure:** Muscle breakdown **Time Frame:** Primarily 5 days - 1 year **Description:** Bun/ Creatinine **Measure:** Renal complications **Time Frame:** Primarily 5 days - 1 year #### Secondary Outcomes **Description:** EHR pain scores **Measure:** Quantitative Pain Outcomes **Time Frame:** 14 days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria 1. Diagnosis of rhabdomyolysis defined as creatine kinase\> 5000 with trauma excluded 2. Ability of parents/patients to understand and the willingness to sign a written informed consent document. 3. Patients ages 12 and older will sign written assent Exclusion Criteria: * Already taking systemic steroids. * Inability to comply with study instructions. * Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements. * Pregnant women. o A urine pregnancy test will be performed for women of child-bearing potential. * Below gestational age of 40 weeks * Allergy to fluconazole, clotrimazole or nystatin. * Cannot tolerate PO medications **Maximum Age:** 25 Years **Minimum Age:** 6 Months **Sex:** ALL **Standard Ages:** - CHILD - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Washington **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Natasha Shur - **Phone:** 202-545-2515 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Seth Berger - **Phone:** 202 476-6156 - **Role:** CONTACT **Country:** United States **Facility:** Childrens National **State:** District of Columbia **Zip:** 20010 ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Chavez LO, Leon M, Einav S, Varon J. Beyond muscle destruction: a systematic review of rhabdomyolysis for clinical practice. Crit Care. 2016 Jun 15;20(1):135. doi: 10.1186/s13054-016-1314-5. **PMID:** 27301374 **Citation:** Summerlin ML, Regier DS, Fraser JL, Chapman KA, Kafashzadeh D, Billington C Jr, Kisling M, Grochowsky A, Ah Mew N, Shur N. Use of dexamethasone in idiopathic, acute pediatric rhabdomyolysis. Am J Med Genet A. 2021 Feb;185(2):500-507. doi: 10.1002/ajmg.a.62000. Epub 2020 Dec 10. **PMID:** 33300687 **Citation:** Szugye HS. Pediatric Rhabdomyolysis. Pediatr Rev. 2020 Jun;41(6):265-275. doi: 10.1542/pir.2018-0300. **PMID:** 32482689 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009135 - Term: Muscular Diseases - ID: D000009140 - Term: Musculoskeletal Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases ### Condition Browse Module - Browse Leaves - ID: M15035 - Name: Rhabdomyolysis - Relevance: HIGH - As Found: Rhabdomyolysis - ID: M12092 - Name: Muscular Diseases - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000012206 - Term: Rhabdomyolysis ### Intervention Browse Module - Ancestors - ID: D000000893 - Term: Anti-Inflammatory Agents - ID: D000000932 - Term: Antiemetics - ID: D000001337 - Term: Autonomic Agents - ID: D000018373 - Term: Peripheral Nervous System Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000005765 - Term: Gastrointestinal Agents - ID: D000005938 - Term: Glucocorticoids - ID: D000006728 - Term: Hormones - ID: D000006730 - Term: Hormones, Hormone Substitutes, and Hormone Antagonists - ID: D000018931 - Term: Antineoplastic Agents, Hormonal - ID: D000000970 - Term: Antineoplastic Agents ### Intervention Browse Module - Browse Branches - Abbrev: Infl - Name: Anti-Inflammatory Agents - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: AnEm - Name: Antiemetics - Abbrev: Gast - Name: Gastrointestinal Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M7102 - Name: Dexamethasone - Relevance: HIGH - As Found: Children - ID: M235549 - Name: Dexamethasone acetate - Relevance: LOW - As Found: Unknown - ID: M199152 - Name: BB 1101 - Relevance: LOW - As Found: Unknown - ID: M4217 - Name: Anti-Inflammatory Agents - Relevance: LOW - As Found: Unknown - ID: M4251 - Name: Antiemetics - Relevance: LOW - As Found: Unknown - ID: M8881 - Name: Gastrointestinal Agents - Relevance: LOW - As Found: Unknown - ID: M9047 - Name: Glucocorticoids - Relevance: LOW - As Found: Unknown - ID: M9789 - Name: Hormones - Relevance: LOW - As Found: Unknown - ID: M9788 - Name: Hormone Antagonists - Relevance: LOW - As Found: Unknown - ID: M20966 - Name: Antineoplastic Agents, Hormonal - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000003907 - Term: Dexamethasone ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429969 **Acronym:** NMR **Brief Title:** Metabolomic Profile of Vitreoretinal Diseases: an NMR-Based Approach Using Vitreous. **Official Title:** Nuclear Magnetic Resonance (NMR)-Based Metabolomic Characterisation of Vitreoretinal Diseases Using Vitreous Fluid #### Organization Study ID Info **ID:** WDRY2022-K222 #### Organization **Class:** OTHER **Full Name:** Renmin Hospital of Wuhan University ### Status Module #### Completion Date **Date:** 2027-12-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-21 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2027-04-17 **Type:** ESTIMATED #### Start Date **Date:** 2024-01-17 **Type:** ACTUAL **Status Verified Date:** 2024-01 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Renmin Hospital of Wuhan University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** The goal of this observational study was to learn about metabolomics profiles in vitreoretinal diseases by nuclear magnetic resonance (NMR)using vitreous fluid. The main question it aimed to answer was abnormal biomarkers for common retinal diseases such as idiopathic macular hole(IMH), diabetic retinopathy(DR) and retinal detachment(RD). Participants would not be subjected to any intervention and the investigators would only collect preoperative information and remaining vitreous samples. The investigators divided the participants into groups with appropriate disease names based on the disease diagnosis, such as IMH group, DR group, and RD group. The MH group was used as a control group, investigators compared other groups to see the metabolomic abnormalities. **Detailed Description:** This study aimed to analyze vitreous fluid using NMR to discover potential biomarkers for the prevention, early diagnosis, and treatment of vitreoretinal diseases and to reveal the mechanisms of disease progression. Patients suffering from IMH, DR, RD, idiopathic macular epiretinal membrane (IMM), and retinal vein occlusion (RVO) quiring for pars plana vitrectomy (PPV), who visited Renmin Hospital of Wuhan University, were chosen to participate in this study. Participants were not subjected to any intervention and the investigator only collected preoperative information and remaining vitreous samples. Participants provided preoperative examination information and medical history, and the investigators divided the participants into five groups with corresponding disease names based on the disease diagnosis, including five groups for five diseases: IMH group, DR group, RD group, IMM group, and RVO group. The control group for the diseases was the IMH group, and metabolomic differences were observed. These patients are usually treated with PPV, during PPV typically performed on these patients, vitreous fluid is usually disposed of as waste, and investigators collected 100-250 ul of the fluid for NMR analysis to see metabolomic characterization of these diseases. ### Conditions Module **Conditions:** - Vitreoretinal Disease ### Design Module #### Bio Spec **Description:** The vitreous body is a transparent gel composed mainly of fibrous collagen and hydrophilic hyaluronic acid, with a volume of approximately 4.5 ml, constituting the largest volume in the eye. When patients suffer from vitreoretinal diseases such as IMH, DR, RD, IMM, RVO, PPV is usually required so that it can constitute a passageway to allow instruments to enter the retina for manipulation, at which point the vitreous is disposed of as waste. **Retention:** SAMPLES_WITHOUT_DNA #### Design Info **Observational Model:** CASE_CONTROL **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 450 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants diagnosed with idiopathic macular hole(IMH) requiring PPV were enrolled in the IMH group, and this group was a control group because the vitreous of IMH may be closest to normal and normal people do not undergo PPV. 100-250ul of vitreous fluid was collected intraoperatively for NMR analysis. **Label:** IMH group #### Arm Group 2 **Description:** In patients with a confirmed diagnosis of diabetic retinopathy (DR) and requiring PPV surgery, 100-250ul of vitreous fluid was collected intraoperatively for NMR analysis. **Label:** DR group #### Arm Group 3 **Description:** In patients with a confirmed diagnosis of retinal detachment (RD) and requiring PPV surgery, 100-250ul of vitreous fluid was collected intraoperatively for NMR analysis. **Label:** RD group #### Arm Group 4 **Description:** In patients with a confirmed diagnosis of idiopathic macular epiretinal membrane (IMM) and requiring PPV surgery, 100-250ul of vitreous fluid was collected intraoperatively for NMR analysis. **Label:** IMM group #### Arm Group 5 **Description:** In patients with a confirmed diagnosis of retinal vein occlusion (RVO) and requiring PPV surgery, 100-250ul of vitreous fluid was collected intraoperatively for NMR analysis. **Label:** RVO group ### Outcomes Module #### Primary Outcomes **Description:** NMR provides spectral data to show the relative concentration of various amino acids, and the use of NMR to measure vitreous humor and compare changes in amino acid content across disease species leads to speculation about biological markers of disease progression. **Measure:** Relative amino acid concentration(Unite: %) **Time Frame:** intraoperative #### Secondary Outcomes **Description:** Macromolecules such as glucose and lipids also play a role in the metabolism of vitreoretinal diseases, so NMR spectroscopy will be used to show the relative concentration of macromolecules. **Measure:** Relative concentrations of macromolecules such as glucose and lipids(Unite: %) **Time Frame:** intraoperative ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Confirmation of IMH diagnosis with concomitant need for PPV surgery; 2. Confirmation of DR diagnosis with concomitant need for PPV surgery; 3. Confirmation of RD diagnosis with concomitant need for PPV surgery; 4. Confirmation of IMM diagnosis with concomitant need for PPV surgery; 5. Confirmation of RVO diagnosis with concomitant need for PPV surgery. Exclusion Criteria: 1. Diagnosed vitreoretinal disease with no need for PPV surgery; 2. Previous history of PPV surgery; 3. Combination of other active ophthalmic diseases, such as acute conjunctivitis and uveitis; 4. Combination of serious systemic diseases such as hypertension and diabetes mellitus. **Maximum Age:** 90 Years **Minimum Age:** 40 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** The enrolled participants were patients who attended Renmin Hospital of Wuhan University with a confirmed diagnosis of vitreoretinal disease. As a result, most of the participants were residents of Hubei Province, China. It is expected that vitreous fluid samples collected from patients with IMH, DR, RD, IMM, and RVO were 50, 100, 100, 50, and 50, respectively, for a total of 450, with about a mean age of 56 years. ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Liwei Cheng **Phone:** 027-88041911 **Phone Ext:** 86346 **Role:** CONTACT #### Locations **Location 1:** **City:** Wuhan **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Liwei Cheng - **Phone:** 02788041911 - **Phone Ext:** 86346 - **Role:** CONTACT **Country:** China **Facility:** Eye, Center, Renmin Hospital of Wuhan University **State:** Hubei **Status:** RECRUITING **Zip:** 430060 #### Overall Officials **Official 1:** **Affiliation:** Renmin Hospital of Wuhan University **Name:** Lei Du **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Description:** This is not considered for the time being, as further processing of the samples are required subsequently and there may be culling data. **IPD Sharing:** NO ## Derived Section ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429956 **Brief Title:** Combining Treatment Components in Transdiagnostic Therapy for Anxiety and Depression **Official Title:** Combining Treatment Components in Transdiagnostic Therapy for Anxiety and Depression: A Randomized Controlled Trial #### Organization Study ID Info **ID:** Combinatory effects in CBT 24 #### Organization **Class:** OTHER **Full Name:** University of Aarhus ### Status Module #### Completion Date **Date:** 2026-06 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-22 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2026-06 **Type:** ESTIMATED #### Start Date **Date:** 2024-06 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-13 **Study First Submit QC Date:** 2024-05-22 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of Aarhus #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** The present study is a randomized controlled trial that will evaluate the effect of combining two treatment components (i.e., cognitive restructuring and detached mindfulness) drawn from cognitive behavioral therapies (CBTs) that are often combined in clinical practice. However, knowledge about the effect of combining these treatment components is lacking. Therefore, this study aims to explore single, combined, and sequencing effects of these two treatment components in patients with depression and/or anxiety disorders. Furthermore, the study aims to explore possible demographic and clinical moderators of the effects to address the question of what works for whom. **Detailed Description:** A relatively large proportion of psychotherapists endorse practicing eclectic or integrative therapy, drawing from different schools of therapy (Norcross \& Alexander, 2019). This tendency towards integrative therapy has been expressed by former president of the Association of Cognitive and Behavioral Therapies, J. B. Persons, who writes: "We \[clinicians\] rarely proceed through a single protocol from beginning to end. Instead, we use what might be called a mix-and-match strategy, in which we select interventions or modules from one or even two or more protocols that we believe will be helpful to the patient" (Persons, 2005, p. 107). Indeed, there has been a growing research and clinical interest in personalized therapy where treatment components from different therapies are combined with the aim of targeting the symptomatology and theorized maintenance processes of the individual patient (Cohen et al., 2021; DeRubeis et al., 2014; Fisher et al., 2019; Fisher \& Boswell, 2016; Hayes et al., 2022; Huibers et al., 2021; Sauer-Zavala et al., 2022). In addition to this, an increasing number of therapies are designed by combining components from different treatment models (e.g., modular and process-based therapies; Barlow et al., 2018; Hofmann \& Hayes, 2019; Hofmann et al., 2021). As a result, patients are likely to be the recipients of several different techniques or strategies, based on different theoretical models, emphasizing different change principles. However, the extent to which compatibility exists between different treatment components remains an underexplored scientific question. The present study aims to fill this gap. Combining cognitive behavioral therapies Cognitive behavioral therapies (CBTs) are among the most well-researched psychological treatments for anxiety and depressive disorders (Cuijpers, 2017; Cuijpers et al., 2014). While CBT is often viewed as one of the major schools of psychotherapy, specific CBTs differ in their rationale and understanding of the key maintaining processes in psychopathology (Hayes, 2004). A core tenet of traditional CBT, also known as second-wave CBT, is that psychopathology is maintained by maladaptive or irrational thoughts (Beck, 1976). Thus, a commonly used therapeutic component derived from second-wave CBT is cognitive restructuring, where the patient is taught to think more realistically about emotion-evoking situations (Beck et al., 1979; Clark \& Beck, 2010). Thus, cognitive restructuring can be said to target the content of thoughts. In contrast, newer contemporary or so-called third-wave CBTs such as metacognitive therapy (MCT), acceptance and commitment therapy (ACT), and mindfulness-based cognitive therapy (MBCT) target thought processes (Hayes, 2004). A commonly used therapeutic component across third-wave CBTs involves teaching the patient to meet their experiences with mindfulness and acceptance rather than attempting to change their form (termed detached mindfulness in MCT, defusion in ACT, and decentering in MCT; Hayes et al., 2012; Segal et al., 2002; Wells, 2009). Thus, it can be argued that second- and third-wave CBTs reflect very different ways of approaching one's inner life. Despite the differences between second- and third-wave CBTs, treatment components from each wave are often combined. One example of this is the widely employed Unified Protocol (UP) which is a transdiagnostic modular cognitive-behavioral treatment for emotional disorders (e.g., anxiety and depression) (Barlow et al., 2018). In UP, patients are asked to engage in cognitive restructuring (within the treatment module of cognitive flexibility) in one module and to practice detached mindfulness (within the treatment module of mindful emotion awareness) in another (Barlow et al., 2018). Several studies have documented that UP is an effective treatment for anxiety and depression (Longley \& Gleiser, 2023). However, since the treatment modules in UP are rooted in different therapeutic traditions with different rationales, an intriguing question remains whether the treatment modules are in fact compatible. If not, then it is possible that UP is effective not because but rather despite the combination of the treatment modules (O'Toole et al., 2024). Compatibility of components Regarding the combination of mindful emotion awareness and cognitive flexibility, it is theoretically plausible that these modules might be incompatible since the technique of noticing and accepting one's thoughts/emotions (in the module mindful emotion awareness) could be argued to be in opposition to the technique of actively changing one's thoughts (in the module cognitive flexibility). This notion is supported by a small study (N=12) by Gkika and Wells (2015) which investigated the effect of cognitive restructuring and detached mindfulness in an anxiety-provoking situation in patients with elevated symptoms of social anxiety. They found that each technique alone reduced symptoms of social anxiety. However, when combined, a sequencing effect emerged where detached mindfulness followed by cognitive restructuring, but not the reverse, led to increased anxiety (Gkika \& Wells, 2015). Borlimi et al. (2019) similarly demonstrated a sequencing effect. They asked non-clinical participants (N=35) to recall an unpleasant experience and apply either cognitive restructuring or an acceptance technique. Acceptance reduced sympathetic reactivity (i.e., galvanic skin response) more than cognitive restructuring, and importantly, the effect was significantly larger when acceptance followed cognitive restructuring than vice versa (Borlimi et al., 2019). The studies by Gkika and Wells (2015) and Borlimi et al. (2019) are both laboratory experimental studies. The question thus remains whether and how their findings can be generalized to a clinical context with longer duration of each treatment component. Only one larger intervention study exploring combinatory and sequencing effects exists. In this study, Brose et al. (2023) investigated the effect of internet-based cognitive restructuring and behavioral activation on symptoms of depression delivered over 6 weeks. Individuals with mild to moderate depressive symptoms (N=2,304) were randomized to one of two treatment arms, one receiving behavioral activation followed by cognitive restructuring, the other vice versa. The groups had similar dropout rates and showed similar improvements over time, indicating no incongruency between those two components. Besides differences in size and setting (experimental vs. actual treatment), the study by Brose et al. (2023) also differs from the other clinical studies by testing a "cognitive" component against a "behavioral" component instead of comparing different "cognitive" components (e.g., cognitive restructuring and detached mindfulness) against each other. In this case, the rationales may be more consistent with each other. Taken together, the research findings described above, coupled with results from the few other available studies of combinatory effects (Dibbets et al., 2012; Woelk et al., 2022), testify that combining otherwise effective stand-alone treatment components 1) does not necessarily yield an additive effect, 2) may even sometimes detract from a positive outcome, and 3) that the combined effect may depend on the order of the components. Thus, to be able to combine different treatment components for anxiety and depression effectively, there is a need for intervention studies examining single, combined, and sequencing effects for treatment components from different therapies that are often combined. Currently, such research is sparse, thereby motivating the present study. Moreover, understanding for whom these effects are likely to occur is important for the appropriate adaptations of therapeutic interventions to fit the needs of the individual patients (i.e., personalized therapy; Cohen et al., 2021). Aims and hypotheses The primary aim of the present study is to explore the effect of combining treatment components drawn from different CBTs. Thus, we will explore single, combined, and sequencing effects of two treatment modules (i.e., mindful emotion awareness and cognitive flexibility). These modules are routinely delivered together in UP for patients with anxiety disorders or MDD. It is hypothesized that both mindful emotion awareness and cognitive flexibility, when delivered individually, will be effective in reducing symptoms of anxiety and depression. The study will take an exploratory stance regarding combined and sequencing effects and will explore if combined effects are best understood as non-additive, additive, synergistic or antagonistic (cf. O'Toole et al., 2024). A secondary aim of the study is to explore possible demographic and clinical moderators of the effects (e.g., primary diagnosis, baseline cognitive function and symptomatology) to address the question of what works for whom. ### Conditions Module **Conditions:** - Depression - Anxiety ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Participants will be randomized to receive either 1) the mindful emotion awareness module followed by the cognitive flexibility module or 2) the cognitive flexibility module followed by the mindful emotion awareness module. All participants will undergo a three-week waiting period before starting treatment. ##### Masking Info **Masking:** SINGLE **Masking Description:** It will not be known to participants that we are testing combinatory and sequencing effects and that participants are randomly allocated to receive the treatment modules in a specific order. **Who Masked:** - PARTICIPANT **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 93 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants will receive 6 therapy sessions starting with 3 sessions of mindful emotion awareness followed by 3 sessions of cognitive flexibility. Each session will have a duration of approximately 1 hour. Treatment will follow the UP manual by Barlow et al. (2018). **Intervention Names:** - Behavioral: Mindful emotion awareness - Behavioral: Cognitive flexibility **Label:** Order 1 (mindful emotion awareness + cognitive flexibility) **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Participants will receive 6 therapy sessions starting with 3 sessions of cognitive flexibility followed by 3 sessions of mindful emotion awareness. Each session will have a duration of approximately 1 hour. Treatment will follow the UP manual by Barlow et al. (2018). **Intervention Names:** - Behavioral: Mindful emotion awareness - Behavioral: Cognitive flexibility **Label:** Order 2 (cognitive flexibility + mindful emotion awareness) **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Order 1 (mindful emotion awareness + cognitive flexibility) - Order 2 (cognitive flexibility + mindful emotion awareness) **Description:** The mindful emotion awareness module will follow the manual by Barlow et al. (2018). In session 1, the participant will receive psychoeducation about the purpose of mindful emotion awareness (i.e., to cultivate present-focused, non-judgmental attention to one's emotional experiences) and will complete an in-session guided meditation exercise which they will be asked to practice daily using an audio file. In session 2 and 3, two additional exercises are introduced. With "mindful mood induction", the participant is instructed to induce emotions and then practice mindful emotion awareness in this context. With "anchoring in the present", the participant is taught four steps to help them use mindful emotion awareness to pull themself back to the present whenever they feel an emotional response start to build in their everyday life. For homework, the participant will practice mindful emotion using these exercises and the audio file. **Name:** Mindful emotion awareness **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - Order 1 (mindful emotion awareness + cognitive flexibility) - Order 2 (cognitive flexibility + mindful emotion awareness) **Description:** The cognitive flexibility module will follow the manual by Barlow et al. (2018) which is based on the principles by Beck (1976). In session 1, the participant will be psychoeducated about the purpose of cognitive flexibility (i.e., to encourage flexible thinking through reappraisal of one's automatic thinking), and how their thoughts influence their emotional reactions. For homework, the participant will be asked to monitor their automatic thoughts. In session 2, the participant will be introduced to the technique of cognitive flexibility (i.e., generating other possible interpretations), and this technique will be practiced throughout session 2 and 3. For homework, the participant will continue to monitor their automatic thoughts and generate and record other possible interpretations. **Name:** Cognitive flexibility **Type:** BEHAVIORAL ### Outcomes Module #### Other Outcomes **Description:** The Anxiety and Related Disorders Interview Schedule for DSM-5 (ADIS-5; Brown \& Barlow, 2014) will be used to confirm a diagnosis of an anxiety disorder or MDD and establish the number of episodes, onset age, and potential comorbid disorders. The interview will also be used to confirm that none of the above listed reasons for exclusion are present (e.g., bipolar disorder, current or past psychosis). **Measure:** Clinical diagnosis (ADIS-5) **Time Frame:** Baseline only **Description:** Trail Making Test part A (TMT-A; Reitan, 1958). **Measure:** Objective cognitive function - processing speed (TMT-A) **Time Frame:** Baseline only **Description:** Wechsler Adult Intelligence Scale - Fourth Edition, Coding (WAIS-IV coding; Wechsler, 2008). **Measure:** Objective cognitive function - processing speed (WAIS-IV coding) **Time Frame:** Baseline only **Description:** Wechsler Adult Intelligence Scale - Fourth Edition, Digit span (WAIS-IV Digit span; Wechsler, 2008). **Measure:** Objective cognitive function - attention and working memory (WAIS-IV Digit span) **Time Frame:** Baseline only **Description:** Controlled Oral Word Association Test (COWAT; Harrison et al., 2000). **Measure:** Objective cognitive function - executive function (COWAT) **Time Frame:** Baseline only **Description:** Trail Making Test part B (TMT-B; Reitan, 1958). **Measure:** Objective cognitive function - executive function (TMT-B) **Time Frame:** Baseline only **Description:** The Stroop Color and Word Test (STROOP; Stroop, 1935). **Measure:** Objective cognitive function - executive function (STROOP) **Time Frame:** Baseline only **Description:** Wechsler Adult Intelligence Scale - Fourth Edition, Information (WAIS-IV Information; Wechsler, 2008) will be included to control for premorbid intellectual abilities. **Measure:** Objective cognitive function - premorbid intellectual abilities (WAIS-IV Information) **Time Frame:** Baseline only #### Primary Outcomes **Description:** Patient Health Questionnaire-9 (PHQ-9; Kroenke et al., 2001; Spitzer et al., 1999; Spitzer et al., 2000). **Measure:** Depressive symptoms (PHQ-9) **Time Frame:** Development from pre-treatment to post-treatment (6 weeks) **Description:** Beck's Anxiety Inventory (BAI; Beck et al., 1988; Beck \& Steer, 1991). **Measure:** Anxiety symptoms (BAI) **Time Frame:** Development from pre-treatment to post-treatment (6 weeks) **Description:** The General Anxiety Disorder-7 (GAD-7; Spitzer et al., 2006). **Measure:** Symptoms of generalized anxiety disorder (GAD-7) **Time Frame:** Development from pre-treatment to post-treatment (6 weeks) **Description:** The Social Interaction Anxiety Scale (SIAS; Mattick \& Clarke, 1998). **Measure:** Symptoms of social anxiety disorder (SIAS) **Time Frame:** Development from pre-treatment to post-treatment (6 weeks) **Description:** The Panic Disorder Severity Scale - Self-Report Version (PDSS-SR; Houck et al., 2002). **Measure:** Symptoms of panic disorder (PDSS-SR) **Time Frame:** Development from pre-treatment to post-treatment (6 weeks) #### Secondary Outcomes **Description:** Patient Health Questionnaire-9 (PHQ-9; Kroenke et al., 2001; Spitzer et al., 1999; Spitzer et al., 2000). **Measure:** Depressive symptoms (PHQ-9) **Time Frame:** Development from pre-treatment through 3-month follow-up **Description:** Beck's Anxiety Inventory (BAI; Beck et al., 1988; Beck \& Steer, 1991). **Measure:** Anxiety symptoms (BAI) **Time Frame:** Development from pre-treatment through 3-month follow-up **Description:** The General Anxiety Disorder-7 (GAD-7; Spitzer et al., 2006). **Measure:** Symptoms of generalized anxiety disorder (GAD-7) **Time Frame:** Development from pre-treatment through 3-month follow-up **Description:** The Social Interaction Anxiety Scale (SIAS; Mattick \& Clarke, 1998). **Measure:** Symptoms of social anxiety disorder (SIAS) **Time Frame:** Development from pre-treatment through 3-month follow-up **Description:** The Panic Disorder Severity Scale - Self-Report Version (PDSS-SR; Houck et al., 2002). **Measure:** Symptoms of panic disorder (PDSS-SR) **Time Frame:** Development from pre-treatment through 3-month follow-up **Description:** The World Health Organization (WHO)-5 questionnaire (Bech, 1999; Topp et al., 2015). **Measure:** Quality of life (WHO-5) **Time Frame:** Development from pre-treatment to post-treatment and development from pre-treatment through 3-month follow-up **Description:** The Ruminative Response Scale (RRS) brooding subscale (Treynor et al., 2003). **Measure:** Rumination (RRS brooding subscale) **Time Frame:** Development from pre-treatment to post-treatment and development from pre-treatment through 3-month follow-up **Description:** The Penn State Worry Questionnaire (PSWQ; Meyer et al., 1990). **Measure:** Worry (PSWQ) **Time Frame:** Development from pre-treatment to post-treatment and development from pre-treatment through 3-month follow-up **Description:** For in-session questionnaires, the Ambulatory Worry Scale (AWS; Kramer et al., 2021) will be used because it has been specially developed to evaluate state variations in worry. **Measure:** Worry (AWS) **Time Frame:** Session by session development during the 6 weeks of active treatment **Description:** The Experiences Questionnaire (EQ) decentering subscale (Fresco et al., 2007). **Measure:** Decentering (EQ decentering subscale) **Time Frame:** Development from pre-treatment to post-treatment and development from pre-treatment through 3-month follow-up **Description:** Emotion Regulation Questionnaire (ERQ) reappraisal subscale (Gross \& John, 2003). **Measure:** Reappraisal (ERQ) **Time Frame:** Development from pre-treatment to post-treatment and development from pre-treatment through 3-month follow-up **Description:** Five Facet Mindfulness Questionnaire - 15 (FFMQ-15; Baer et al., 2006). **Measure:** Mindfulness (FFMQ-15) **Time Frame:** Development from pre-treatment to post-treatment and development from pre-treatment through 3-month follow-up **Description:** Perceived Deficits Questionnaire - Depression (PDQ-D; Fehnel et al., 2016) **Measure:** Subjective cognitive function (PDQ-D) **Time Frame:** Development from pre-treatment to post-treatment and development from pre-treatment through 3-month follow-up **Description:** Five questions concerning the participants' experience or expectations concerning the components have been developed by the project group due to a lack of such assessment in the field. **Measure:** Experience of therapy **Time Frame:** Session by session development during the 6 weeks of active treatment and through 3-month follow-up **Description:** Working Alliance Inventory - Short Revised (WAI-SR; Munder et al., 2010). **Measure:** Working alliance (WAI-SR) **Time Frame:** Session 3 and 5 only **Description:** The Information Overload (IO) scale, consisting of 8 items. This is our own adaptation of the Cancer Information Overload scale (Jensen et al., 2014) to assess perceived information overload related to the received treatment. This is included in all session questionnaires. **Measure:** Information overload (IO) **Time Frame:** Session by session development during the 6 weeks of active treatment ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Age ≥ 18 years. 2. A diagnosis of an anxiety disorder (generalized anxiety disorder, social anxiety disorder, or panic disorder with or without agoraphobia) and/or mild to moderate major depressive disorder (MDD) according to DSM-5 (American Psychiatric Association, 2022). 3. Danish language proficiency. 4. Ability and willingness to give informed consent. 5. No or stable antidepressant/antianxiety medication (i.e., same dosage for ≥ 8 weeks). 6. Access to either a smartphone, tablet, or computer with video camera. Exclusion Criteria: 1. Severe depression deemed to require more intense psychotherapy or medication. 2. Persistent depressive disorder (i.e., depressive symptoms have persisted for 2 years or more). 3. Non-stabilized medication (see above). 4. Currently receiving other psychotherapy or counseling. 5. Not capable of participating online. 6. Lack of Danish proficiency. 7. A history of bipolar disorder. 8. Current or past psychosis. 9. Substance abuse or dependence judged to require treatment. 10. Suicide risk requiring immediate hospitalization. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Caroline Nørskov, MSc **Phone:** +4587150193 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Mia O'Toole, PhD **Phone:** +4587165289 **Role:** CONTACT #### Overall Officials **Official 1:** **Affiliation:** University of Aarhus **Name:** Caroline Nørskov, MSc **Role:** PRINCIPAL_INVESTIGATOR ## Document Section ### Large Document Module #### Large Docs - Date: 2024-05-13 - Filename: SAP_000.pdf - Has ICF: False - Has Protocol: False - Has SAP: True - Label: Statistical Analysis Plan - Size: 207843 - Type Abbrev: SAP - Upload Date: 2024-05-13T05:33 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001526 - Term: Behavioral Symptoms - ID: D000019964 - Term: Mood Disorders - ID: D000001523 - Term: Mental Disorders ### Condition Browse Module - Browse Branches - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M7061 - Name: Depressive Disorder - Relevance: HIGH - As Found: Depression - ID: M7058 - Name: Depression - Relevance: HIGH - As Found: Depression - ID: M4324 - Name: Anxiety Disorders - Relevance: HIGH - As Found: Anxiety - ID: M4818 - Name: Behavioral Symptoms - Relevance: LOW - As Found: Unknown - ID: M21835 - Name: Mood Disorders - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003863 - Term: Depression - ID: D000003866 - Term: Depressive Disorder - ID: D000001008 - Term: Anxiety Disorders ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429943 **Brief Title:** Cerebrolysin in SAH (Subarachnoidal Haemorrhage) - Observational Study **Official Title:** Cerebrolysin in Patients Diagnosed With SAH - an Observational Cohort Study (PILOT) #### Organization Study ID Info **ID:** SAH/2020/2023 #### Organization **Class:** OTHER **Full Name:** Pomeranian Medical University Szczecin ### Status Module #### Completion Date **Date:** 2023-01-10 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-21 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2022-10-15 **Type:** ACTUAL #### Start Date **Date:** 2021-01-15 **Type:** ACTUAL **Status Verified Date:** 2023-12 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Pomeranian Medical University Szczecin #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Is US Export:** False ### Description Module **Brief Summary:** Subarachnoid haemorrhage often affects people in middle age and is associated with high mortality or neurological damage. In recent years, advances in surgical techniques have im-proved the mortality rate. However, there is still need for the research for the optimal possible final effect of treatment. In our study, we've decided to examine the effect of a multimodal approach including Cerebrolysin in the supportive treatment of patients. We've examined the supply of neuroprotective drugs and neuromonitoring. ### Conditions Module **Conditions:** - SAH (Subarachnoid Hemorrhage) **Keywords:** - SAH - Cerebrolysin - neuromonitoring ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** OTHER #### Enrollment Info **Count:** 47 **Type:** ACTUAL **Patient Registry:** True **Study Type:** OBSERVATIONAL **Target Duration:** 1 Month ### Arms Interventions Module #### Arm Group 1 **Description:** Cerebrolysin administration **Label:** A #### Arm Group 2 **Description:** without Cerebrolysin administration **Label:** B ### Outcomes Module #### Primary Outcomes **Description:** Glasgow Outcome Scale - 5 points scale, characterizing the patients' deficits **Measure:** GOS Glasgow Outcome Scale **Time Frame:** 1 month #### Secondary Outcomes **Description:** length of stay in days, that patient spent in hospital/ intensive care unit **Measure:** LOS Length of Stay **Time Frame:** hospitalisation time **Description:** mortality **Measure:** mortality **Time Frame:** 1 month ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * age \>18 years old, diagnosis of SAH, treatment in ICU conditions Exclusion Criteria: * age \<18 years, medical history of allergy to Cerebrolysin, acute renal failure, pregnancy, multi organ trauma, death within 48 hours after admission **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** The study population is the population of patients diagnosed with SAH, treated in University Hospital no.1 in Szczecin, Poland. Mainly the patients come from the population of westerpomeranian county, but as SAH is an acute disease also patients from the whole region of Poland, treated in the Hospital were included in the study. ### Contacts Locations Module #### Locations **Location 1:** **City:** Szczecin **Country:** Poland **Facility:** Pomeranian Medical University, University Hospital no.1 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000020300 - Term: Intracranial Hemorrhages - ID: D000002561 - Term: Cerebrovascular Disorders - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M16135 - Name: Subarachnoid Hemorrhage - Relevance: HIGH - As Found: Subarachnoid Hemorrhage - ID: M9556 - Name: Hemorrhage - Relevance: HIGH - As Found: Hemorrhage - ID: M22113 - Name: Intracranial Hemorrhages - Relevance: LOW - As Found: Unknown - ID: M5810 - Name: Cerebrovascular Disorders - Relevance: LOW - As Found: Unknown - ID: M5204 - Name: Brain Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000013345 - Term: Subarachnoid Hemorrhage - ID: D000006470 - Term: Hemorrhage ### Intervention Browse Module - Browse Branches - Abbrev: NeuroAg - Name: Neuroprotective Agents - Abbrev: NootAg - Name: Nootropic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M352392 - Name: Cerebrolysin - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429930 **Brief Title:** Safety, Tolerability and Pharmacokinetics Study of L608 in Healthy Adults **Official Title:** A Phase 1, Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses of L608 for Inhalation in Healthy Participants #### Organization Study ID Info **ID:** PBI-L608-B12 #### Organization **Class:** INDUSTRY **Full Name:** Pharmosa Biopharm Inc. ### Status Module #### Completion Date **Date:** 2025-09-30 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-21 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2025-08-14 **Type:** ESTIMATED #### Start Date **Date:** 2024-09-01 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** Novotech (New Zealand) Limited #### Lead Sponsor **Class:** INDUSTRY **Name:** Pharmosa Biopharm Inc. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** This is the second single ascending dose study of L608 in healthy participants and is being conducted to evaluate the safety of L608 with higher dose levels, starting from 20 μg and escalating up to a planned maximum dose of 110 μg. **Detailed Description:** L608 inhalation Solution (L608) is developed by Pharmosa Biopharm Inc. (PBI) as a new liposomal Iloprost formulation for inhalation use in the treatment of patients with WHO Group 1 PAH. As a liposomal formulation of iloprost, L608 is intended to reduce the dosing frequency, as well as provide sustained and selective release along with achieving therapeutically relevant iloprost level. Meanwhile, L608 is expected to mitigate burst release related local irritation and systemic side effects (e.g., hypotension due to plasma peak) in clinical practice. This Phase I, randomized, double-blinded, placebo-controlled study will be conducted in healthy participants in New Zealand to evaluate the safety, tolerability, and pharmacokinetic of L608. The dose escalation design is applied in this study. The sentinel dosing design will be applied for all cohorts. ### Conditions Module **Conditions:** - Pulmonary Arterial Hypertension **Keywords:** - Pulmonary Arterial Hypertension - Hypertension, Pulmonary - Lung Diseases - Respiratory Tract Diseases - Pharmaceutical Solutions ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** SINGLE_GROUP **Intervention Model Description:** Randomized, Placebo-controlled, double-blinded, single ascending dose escalation ##### Masking Info **Masking:** DOUBLE **Masking Description:** This is a double-blinded, single ascending dose escalation design. After confirmation of eligibility, subjects will be randomized at a ratio of 1:1 (for sentinel dosing) followed by 5:1 for rest of the cohorts to receive the assigned dose of L608 or placebo. **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 56 **Type:** ESTIMATED **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Eight participants will be enrolled in each cohort and be randomized to receive assigned dose of L608 or placebo (6:2). **Intervention Names:** - Drug: L608 Liposomal inhalation solution **Label:** L608 Liposomal inhalation solution **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Eight participants will be enrolled in each cohort and be randomized to receive assigned dose of L608 or placebo (6:2). **Intervention Names:** - Drug: Placebo Solution **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - L608 Liposomal inhalation solution **Description:** Participants will be randomized at a ratio of 1:1 (for sentinel dosing) followed by 5:1 for the rest of the cohort to receive the assigned dose of L608 or placebo. **Name:** L608 Liposomal inhalation solution **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** Participants will be randomized at a ratio of 1:1 (for sentinel dosing) followed by 5:1 for the rest of the cohort to receive the assigned dose of L608 or placebo. **Name:** Placebo Solution **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** DLT: Dose-limiting toxicity **Measure:** Percentage of participants with DLT **Time Frame:** 7 days after administration **Description:** TEAEs: treatment emergent adverse events; SAEs: serious adverse events **Measure:** Percentage of participants with TEAEs and SAEs **Time Frame:** 2 weeks after administration **Description:** TEAEs: treatment emergent adverse events; SAEs: serious adverse events **Measure:** Frequency and severity of TEAEs and SAEs **Time Frame:** 2 weeks after administration #### Secondary Outcomes **Description:** Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration **Measure:** AUC0-t **Time Frame:** 24 hours after administration **Description:** Area under the plasma concentration-time curve from time 0 to infinity **Measure:** AUC0-inf **Time Frame:** 24 hours after administration **Description:** AUC extrapolated from the last measurable concentration to infinity as a percentage of total AUC **Measure:** %AUCextrap **Time Frame:** 24 hours after administration **Description:** Maximum observed plasma concentration **Measure:** Cmax **Time Frame:** 24 hours after administration **Description:** Time to reach the maximum observed plasma concentration **Measure:** Tmax **Time Frame:** 24 hours after administration **Description:** Apparent plasma terminal elimination half-life **Measure:** T1/2 **Time Frame:** 24 hours after administration **Description:** Apparent total plasma clearance **Measure:** CL/F **Time Frame:** 24 hours after administration **Description:** Apparent volume of distribution during the terminal phase **Measure:** Vz/F **Time Frame:** 24 hours after administration **Description:** Terminal elimination rate constant **Measure:** λz **Time Frame:** 24 hours after administration **Description:** Dose-normalized Cmax. **Measure:** Cmax/D **Time Frame:** 24 hours after administration **Description:** Dose-normalized AUC0-t. **Measure:** AUC0-t/D **Time Frame:** 24 hours after administration **Description:** Dose-normalized AUC0-inf. **Measure:** AUC0-inf/D **Time Frame:** 24 hours after administration ### Eligibility Module **Eligibility Criteria:** Key Inclusion Criteria: 1. Men and women aged between 18 and 65 (inclusive) at the time of Screening visit. 2. Participants with Body Mass Index (BMI) of ≥18.5 and ≤32.0 kg/m2 and weight of at least 50 kg at Screening. 3. Non-smokers or former smokers who have smoked ≤ 100 cigarettes in their lifetime and have not consumed any tobacco or tobacco-containing products for at least 3 months prior to Screening. 4. Females must not be pregnant or lactating and must use acceptable, highly effective double contraception from Screening until 3 months after the last dose of the Investigational product. Key Exclusion Criteria: 1. Participants with contraindications or sensitivity to any components of the study treatment. 2. Participants with histories or active conditions of unexplained bleeding events, hemoptysis, abnormal bleeding tendencies, and/or coagulation disorders. 3. Participants with histories or active conditions of asthma, sleep apnea, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, bronchiectasis, bronchospasm, and/or reactive airway. Subjects who have had childhood asthma which have resolved as deemed by the PI can be considered. 4. Participants with histories or active conditions of myocardial infarction (MI), cerebrovascular accident (CVA), coronary artery disease (CAD), unstable angina, heart failure, significant cardiac arrhythmias, congenital or acquired valvular heart disease with clinically insignificant symptom, suspected lung congestion, and/or pulmonary arterial hypertension (PAH) causing by venous thromboembolism. 5. Participants with systolic blood pressure \< 90 mmHg or \> 140 mmHg and/or diastolic blood pressure \< 50 mmHg or \> 95 mmHg at Screening or check-in visit. 6. Participants with FEV1 less than 80% predicted, FVC ˂ 80% predicted, or resting oxygen saturation less than 95% at Screening or check-in visit. 7. Participants with histories of drug or alcohol abuse within 1 year prior to subject check-in (Day -1). Regular alcohol consumption defined as \> 14 standard drinks per week for female and \> 21 standard drinks per week for male. 8. Consumption of products containing caffeine/methylxanthines, poppy seeds and/or alcohol within 48 hours before dosing and products containing grapefruit and/or pomelo (shown to inhibit cytochrome P450 \[CYP\] 3A4 activity) within 10 days prior to drug administration, and/or participants unwilling to refrain from consumption of alcohol from 48 hours before dosing to Day 14. 9. Receipt of blood products within 2 months prior to dosing. 10. Positive results of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and pregnancy test. 11. Blood donation or significant blood loss (\>480 ml) within 3 months prior to Screening. 12. Participants unwilling to refrain from strenuous exercises from 7 days prior to dosing until the EOS visit. 13. Participants planning to receive a tattoo, body piercing, or undergo any invasive procedure during the study period. **Healthy Volunteers:** True **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Pei Kan, PhD **Phone:** +886-2-2782-7561 **Phone Ext:** 102 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Sydney Chuang **Phone:** +886-2-2782-7561 **Phone Ext:** 110 **Role:** CONTACT #### Locations **Location 1:** **City:** Christchurch **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Christopher John Wynne - **Phone:** +64 3 372-9477 - **Role:** CONTACT **Country:** New Zealand **Facility:** NZCR Ltd (New Zealand Clinical Research) **Zip:** 8011 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000006976 - Term: Hypertension, Pulmonary - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10024 - Name: Hypertension - Relevance: HIGH - As Found: Hypertension - ID: M2261 - Name: Pulmonary Arterial Hypertension - Relevance: HIGH - As Found: Pulmonary Arterial Hypertension - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M10027 - Name: Hypertension, Pulmonary - Relevance: LOW - As Found: Unknown - ID: M27137 - Name: Respiratory Aspiration - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: T4807 - Name: Pulmonary Arterial Hypertension - Relevance: HIGH - As Found: Pulmonary Arterial Hypertension ### Condition Browse Module - Meshes - ID: D000081029 - Term: Pulmonary Arterial Hypertension - ID: D000006973 - Term: Hypertension ### Intervention Browse Module - Browse Branches - Abbrev: PhSol - Name: Pharmaceutical Solutions - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M21860 - Name: Pharmaceutical Solutions - Relevance: HIGH - As Found: Procedure ### Intervention Browse Module - Meshes - ID: D000019999 - Term: Pharmaceutical Solutions ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429917 **Brief Title:** Impact of Subgingival Instrumentation on Jaw Symptoms of Probable Bruxers Among Patients With Periodontitis **Official Title:** Impact of Subgingival Instrumentation on Jaw Symptoms of Probable Bruxers Among Patients With Periodontitis- An Interventional Study #### Organization Study ID Info **ID:** PGIDS/BHRC/24/37 #### Organization **Class:** OTHER **Full Name:** Postgraduate Institute of Dental Sciences Rohtak ### Status Module #### Completion Date **Date:** 2025-09 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-21 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2025-08 **Type:** ESTIMATED #### Start Date **Date:** 2024-08 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Postgraduate Institute of Dental Sciences Rohtak #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study aims to explore the mechanisms by which periodontal disease affects the bruxers and to assess the impact of subgingival instrumentation on jaw symptoms of probable bruxers among patients with periodontitis . **Detailed Description:** Patients with chronic periodontitis usually describe itching and persistent pain of moderate intensity. Applying masticatory pressure provides relief in these symptoms. However, this practice may lead to the development of bruxism habits in patients over time. A deeper comprehension of the dynamic interplay between periodontal health and bruxism is crucial for crafting holistic treatment approaches aimed at addressing both symptoms and root causes effectively. Till now, there has been no report examining the effect of subgingival instrumentation on probable bruxers in periodontitis patients. . This study aims to assess the impact of subgingival instrumentation on jaw symptoms of probable bruxers in patients with periodontitis ### Conditions Module **Conditions:** - Periodontitis - Bruxism **Keywords:** - Inflammation ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 60 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** All the participants will undergo subgingival instrumentation with hand scalers, curettes and ultrasonic scaler. Parameters will be recorded at baseline and two, three and six months of time points after subgingival instrumentation. **Intervention Names:** - Other: Subgingival instrumentation **Label:** Periodontitis with bruxism **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - Periodontitis with bruxism **Description:** All the participants will undergo subgingival instrumentation with hand scalers, curettes and ultrasonic scaler. Parameters will be recorded at baseline and two, three and six months of time points after subgingival instrumentation. **Name:** Subgingival instrumentation **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Improvement in frequency and intensity of Jaw Symptoms (pain, unpleasantness, sensitivity, tiredness, tension and stiffness) as perceived by the patient. **Measure:** Jaw symptoms **Time Frame:** baseline , 2 months , 3 months and 6 months #### Secondary Outcomes **Description:** BOP recorded as 1 if bleeding occurs within 15 seconds of probing and 0 (absent) if no bleeding occurred. It will be calculated in %. After adding all the scores, total score will be divided by the total no. of surfaces accessed and multiplied by 100 **Measure:** Bleeding on probing **Time Frame:** baseline , 2 months , 3 months and 6 months **Description:** Gingival index by Loe and Silness (1963) will be used to assess severity of gingival inflammation. **Measure:** Gingival index **Time Frame:** baseline , 2 months , 3 months and 6 months **Description:** Probing Pocket Depth (PPD): Probing pocket depth will be measured as the distance from gingival margin to the base of pocket. The probing depth measurements will be assessed using the Periodontal probe. The probe will be inserted in the bottom of pocket and maintained parallel to vertical axis of the tooth. Measurements will be noted at 6sites of a tooth (mesio-buccal, mid-buccal, disto- buccal, mesio-lingual, mid-lingual and disto- lingual). Measurements will be rounded to the nearest whole millimeter. **Measure:** Probing pocket depth **Time Frame:** baseline , 2 months , 3 months and 6 months **Description:** Tooth mobility is assessed using Miller Mobility Index **Measure:** tooth mobility **Time Frame:** baseline , 2 months , 3 months and 6 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * 1. Systemically healthy patients 2. Patient having habit of bruxism diagnosed with periodontitis 3. Age between 30-40 years 4. Minimum 20 teeth present in oral cavity Exclusion Criteria: 1. History of systemic disease such as diabetes or autoimmune disease 2. History of drugs having the potential impact on periodontal status like phenytoin, cyclosporin, calcium-channel blockers or antidepressant drugs. 3. Pregnant or lactating females. 4. Post-menopausal women. 5. Patients diagnosed with temporomandibular disorders- pain and tenderness in the masticatory muscles 6. Patients receiving interventions for bruxism. 7. History of Psychological disorders **Healthy Volunteers:** True **Maximum Age:** 40 Years **Minimum Age:** 30 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** RAJINDER KR SHARMA, MDS **Phone:** 9416358222 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** VARSHA KAPOOR, BDS **Phone:** 9991802339 **Role:** CONTACT #### Locations **Location 1:** **City:** Rohtak **Country:** India **Facility:** Post Graduate Institute of Dental Sciences **State:** Haryana **Zip:** 124001 #### Overall Officials **Official 1:** **Affiliation:** PGIDS, ROHTAK **Name:** VARSHA KAPOOR, BDS **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010510 - Term: Periodontal Diseases - ID: D000009059 - Term: Mouth Diseases - ID: D000009057 - Term: Stomatognathic Diseases - ID: D000014076 - Term: Tooth Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC07 - Name: Mouth and Tooth Diseases ### Condition Browse Module - Browse Leaves - ID: M10293 - Name: Inflammation - Relevance: LOW - As Found: Unknown - ID: M13427 - Name: Periodontitis - Relevance: HIGH - As Found: Periodontitis - ID: M5286 - Name: Bruxism - Relevance: HIGH - As Found: Bruxism - ID: M13419 - Name: Periodontal Diseases - Relevance: LOW - As Found: Unknown - ID: M12019 - Name: Mouth Diseases - Relevance: LOW - As Found: Unknown - ID: M12017 - Name: Stomatognathic Diseases - Relevance: LOW - As Found: Unknown - ID: M16831 - Name: Tooth Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000010518 - Term: Periodontitis - ID: D000002012 - Term: Bruxism ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429904 **Brief Title:** Nimotuzumab Plus NALIRIFOX in Locally Advanced Pancreatic Cancer **Official Title:** A Prospective, Single Arm Study of Nimotuzumab Combined With NALIRIFOX in the Treatment of Locally Advanced Pancreatic Cancer #### Organization Study ID Info **ID:** IST-Nim-PC-29 #### Organization **Class:** OTHER **Full Name:** Peking Union Medical College Hospital ### Status Module #### Completion Date **Date:** 2027-05 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-21 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2027-05 **Type:** ESTIMATED #### Start Date **Date:** 2024-05-15 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Peking Union Medical College Hospital #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** This is a prospective, open-label, single arm clinical study. The main purpose of the study is to evaluate the clinical efficacy and safety of Nimotuzumab combined with NALIRIFOX in the treatment of locally advanced pancreatic cancer (LAPC). **Detailed Description:** This clinical study is designed as a prospective, open-label, single arm study to evaluate the clinical efficacy and safety of Nimotuzumab combined with NALIRIFOX in the treatment of locally advanced pancreatic cancer (LAPC). Patients will receive Nimotuzumab plus NALIRIFOX as conversion therapy, and imaging assessments (according to RECIST V.1.1 criteria) will be performed every two cycles (every two months) of conversion therapy. The resectability of the primary pancreatic lesion will be judged based on NCCN guidelines and will be determined by a multidisciplinary team of experts. The main endpoint is overall survival (OS). Additional end points included resection rates, progression-free survival (PFS), objective response rate (ORR), safety, etc. ### Conditions Module **Conditions:** - Locally Advanced Pancreatic Cancer **Keywords:** - Nimotuzumab - locally advanced pancreatic cancer ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 31 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Nimotuzumab combined with NALIRIFOX in the treatment of locally advanced pancreatic cancer **Intervention Names:** - Drug: Nimotuzumab+ NALIRIFOX **Label:** Nimotuzumab combined with NALIRIFOX **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Nimotuzumab combined with NALIRIFOX **Description:** Drug: Nimotuzumab Patients will receive Nimotuzumab 400 mg weekly or Nimotuzumab 600mg, 600mg, 400mg on Day 1, 8, 15, respectively, 28 days as a cycle, up to 6 cycles. Other Names: h-R3 Drug: NALIRIFOX Patients will receive NALIRIFOX (liposomal irinotecan 50 mg/m2, oxaliplatin 60 mg/m2, leucovorin 400 mg/m2, and fluorouracil 2400 mg/m2, administered sequentially as a continuous intravenous infusion over 46 h) on days 1 and 15 of a 28-day cycle, up to 6 cycles. Other Names: NALIRIFOX **Name:** Nimotuzumab+ NALIRIFOX **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The time from the beginning of treatment to death due to any cause. **Measure:** overall survival (OS) **Time Frame:** Up to 24 months #### Secondary Outcomes **Description:** The proportion of patients who underwent surgery. **Measure:** resection rate **Time Frame:** Up to 24 months **Description:** PFS, defined as the time from the beginning of treatment to disease progression or all-cause death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. **Measure:** progression-free survival (PFS) **Time Frame:** Up to 24 months **Description:** Objective response rate (ORR), including complete response (CR) and partial response (PR). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions. **Measure:** Objective response rate (ORR) **Time Frame:** Up to 12 months **Description:** To explore the influence of tumor-related markers such as CA199 and EGFR on prognosis. **Measure:** tumor-related markers **Time Frame:** Up to 24 months **Description:** Frequency and severity of adverse events. **Measure:** adverse events **Time Frame:** Up to 30 days after last administration ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Age 18-75 years old, gender unlimited; 2. Histologically or cytologically confirmed pancreatic ductal adenocarcinoma (PDAC); 3. Locally advanced pancreatic cancer, no evidence of distant metastasis as demonstrated by imaging; 4. Receive nimotuzumab and NALIRIFOX for voluntary, and patients can tolerate NALIRIFOX by researcher's evaluation; 5. No prior tumor systemic therapy. 6. Measurable disease according to RECIST criteria v1.1; 7. Adequate organ and bone marrow function, defined as follows: hemoglobin≥9.0 g/dL; absolute neutrophil count (ANC)≥1.5×10\^9/L; platelets≥100×10\^9/L; serum total bilirubin (TBIL)≤1.5×ULN; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times the upper limit of normal (ULN); serum creatinine≤1.5×ULN or estimated creatinine clearance \> 60 mL/min; 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; 9. Postoperative survival was expected to be ≥3 months; 10. Fertile subjects are willing to take contraceptive measures during the study period. 11. Good compliance and signed informed consent voluntarily. Exclusion Criteria: 1. Refuse chemotherapy or surgery; 2. History of other malignancies (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix); 3. Accompanied by other serious diseases, including but not limited to: compensatory heart failure (NYHA grade III and IV), unstable angina, poorly controlled arrhythmias, uncontrolled hypertension (SBP\>160mmHg or DBP\>100mmHg); active infections; unmanageable diabetes mellitus; presence of uncontrolled pleural effusion, pericardial effusion, or ascites requiring drainage; severe portal hypertension; gastric outlet obstruction; Respiratory insufficiency; 4. Undergone major surgery within 30 days; 5. Use of EGFR-mab or EGFR-TKI within 30 days; 6. Known allergy to prescription or any component of the prescription used in this study; 7. With HIV, HPV, or syphilis infection, or active hepatitis (hepatitis B, hepatitis C) 8. Other reasons that are not suitable to participate in this study according to the researcher's judgment **Maximum Age:** 75 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Beijing **Country:** China **Facility:** Peking Union Medical College Hospital ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000004067 - Term: Digestive System Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000004701 - Term: Endocrine Gland Neoplasms - ID: D000004066 - Term: Digestive System Diseases - ID: D000010182 - Term: Pancreatic Diseases - ID: D000004700 - Term: Endocrine System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M13110 - Name: Pancreatic Neoplasms - Relevance: HIGH - As Found: Pancreatic Cancer - ID: M8886 - Name: Gastrointestinal Neoplasms - Relevance: LOW - As Found: Unknown - ID: M7256 - Name: Digestive System Neoplasms - Relevance: LOW - As Found: Unknown - ID: M7863 - Name: Endocrine Gland Neoplasms - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M13102 - Name: Pancreatic Diseases - Relevance: LOW - As Found: Unknown - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown - ID: T4387 - Name: Pancreatic Cancer - Relevance: HIGH - As Found: Pancreatic Cancer ### Condition Browse Module - Meshes - ID: D000010190 - Term: Pancreatic Neoplasms ### Intervention Browse Module - Ancestors - ID: D000074322 - Term: Antineoplastic Agents, Immunological - ID: D000000970 - Term: Antineoplastic Agents ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Micro - Name: Micronutrients ### Intervention Browse Module - Browse Leaves - ID: M1674 - Name: Oxaliplatin - Relevance: LOW - As Found: Unknown - ID: M1671 - Name: Irinotecan - Relevance: LOW - As Found: Unknown - ID: M8600 - Name: Fluorouracil - Relevance: LOW - As Found: Unknown - ID: M6191 - Name: Leucovorin - Relevance: LOW - As Found: Unknown - ID: M288889 - Name: Nimotuzumab - Relevance: HIGH - As Found: Details - ID: M1346 - Name: Antineoplastic Agents, Immunological - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000501466 - Term: Nimotuzumab ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429891 **Brief Title:** Research on Early Diagnosis and Clinical Transformation of Nuclide Probe Based on Bioorthogonal-gastric Cancer Mucin Target Visualization **Official Title:** Research on Early Diagnosis and Clinical Transformation of Nuclide Probe Based on Bioorthogonal-gastric Cancer Mucin Target Visualization #### Organization Study ID Info **ID:** 2024KT68 #### Organization **Class:** OTHER **Full Name:** Peking University Cancer Hospital & Institute ### Status Module #### Completion Date **Date:** 2026-12 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-21 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2026-12 **Type:** ESTIMATED #### Start Date **Date:** 2024-05 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Hua Zhu #### Responsible Party **Investigator Affiliation:** Peking University Cancer Hospital & Institute **Investigator Full Name:** Hua Zhu **Investigator Title:** Principal Investigator **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** The symptoms of early gastric cancer are extremely insidious and most patients are identified as advanced at the time of initial diagnosis. Starting from the clinical needs, this project selects solid tumors and pathogenic glycoprotein synthesis of key glycopeptide antigen determinant mucin (MUC) family of multiple molecules as the research object. Based on the digestive system tumor research cohort established in the early stage, this project intends to verify the tumor microenvironment characteristics of the MUC family and gastric cancer treatment resistance through immunohistochemistry, COSMC gene sequencing and other technologies, and screen key MUC family proteins. Based on the discovery of differential recognition of COSMC deficient cells by antibodies, MUC1-targeted specific monoclonal antibody was developed. Further development of spatial mucinomics based on laser ablation inductively coupled plasma mass spectrometry (LA-IPC-MS) and spatial metabolome based on desorption electrospray mass spectrometry (DESI-MS) to analyze the structure and immunosuppressive mechanism of key gastric cancer glycoprotein MUC. After obtaining key targeted antibodies, with the help of biological orthogonal and click chemistry technology, the original clinical translational research based on mucin targeting was carried out, and a high-affinity nuclide conjugate drug (RDC) with "triple binding" of gastric cancer mucin was constructed and clinical translational research was carried out, which provided new ideas for the accurate diagnosis and treatment of gastric cancer in the early stage. ### Conditions Module **Conditions:** - Solid Tumor ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 50 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** All study participants will be allocated to this arm (single-arm study). Study participants will undergo 89Zr-16A PET/CT scans. **Intervention Names:** - Drug: 18F-FDG **Label:** 89Zr-16A **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - 89Zr-16A **Description:** All study participants will undergo one 18F-FDG PET/CT scan. **Name:** 18F-FDG **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The uptake of the tracer (89Zr-16A) in solid tumor lesions or suspected tumor lesions by measuring SUV on PET/CT. **Measure:** Standardized uptake value (SUV) **Time Frame:** 2 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Aged ≥18 years old; ECOG 0 or 1; 2. Patients with solid tumor confirmed by histopathology; 3. Patients with imaging confirmed measurable lesions; 4. life expectancy \>=12 weeks. Exclusion Criteria: 1. Significant hepatic or renal dysfunction; 2. ls pregnant or ready to pregnant; 3. Cannot keep their states for half an hour; 4. Refusal to join the clinical study; 5. Suffering from claustrophobia or other mental diseases； 6. Any other situation that researchers think it is not suitable to participate in the experiment. **Maximum Age:** 70 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Hua Zhu **Phone:** +861088196495 **Role:** CONTACT #### Locations **Location 1:** **City:** Beijing **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Hua Zhu, Dr. - **Phone:** +861088196495 - **Role:** CONTACT **Country:** China **Facility:** Beijing Cancer Hospital **State:** Beijing **Zip:** 100142 #### Overall Officials **Official 1:** **Affiliation:** Peking University Cancer Hospital & Institute **Name:** Hua Zhu **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000005770 - Term: Gastrointestinal Neoplasms - ID: D000004067 - Term: Digestive System Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000004066 - Term: Digestive System Diseases - ID: D000005767 - Term: Gastrointestinal Diseases - ID: D000013272 - Term: Stomach Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M16064 - Name: Stomach Neoplasms - Relevance: HIGH - As Found: Gastric Cancer - ID: M8886 - Name: Gastrointestinal Neoplasms - Relevance: LOW - As Found: Unknown - ID: M7256 - Name: Digestive System Neoplasms - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M16062 - Name: Stomach Diseases - Relevance: LOW - As Found: Unknown - ID: T5486 - Name: Stomach Cancer - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000013274 - Term: Stomach Neoplasms ### Intervention Browse Module - Ancestors - ID: D000019275 - Term: Radiopharmaceuticals - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M21686 - Name: Fluorodeoxyglucose F18 - Relevance: HIGH - As Found: Towards - ID: M21258 - Name: Radiopharmaceuticals - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000019788 - Term: Fluorodeoxyglucose F18 ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429878 **Brief Title:** The Long Term Effect of MRI Before Radical Prostatectomy. **Official Title:** The Long Term Effect of MRI Before Radical Prostatectomy. #### Organization Study ID Info **ID:** 248365 #### Organization **Class:** OTHER **Full Name:** Oslo University Hospital ### Status Module #### Completion Date **Date:** 2026-05-19 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-21 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2012-06-30 **Type:** ACTUAL #### Start Date **Date:** 2009-12-01 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Oslo University Hospital #### Responsible Party **Investigator Affiliation:** Oslo University Hospital **Investigator Full Name:** Erik Rud **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** A randomized clinical trial conducted by Oslo University Hospital between 2010 and 2012 included 438 patients with prostate cancer to the non-MRI group (216) or the MRI group (222) before robot-assisted radical prostatectomy (RALP). The primary endpoint was to compare the nerve-sparing surgery types and the proportion of positive surgical margins (PSM) in each group. The MRI group underwent more non-nerve sparing surgery, whereas the proportion of PSM was similar in both groups (p=0.4) \[1\]. Since the long-term effects of preoperative MRI are unknown, we aimed to assess the variations in the long-term functional and oncological outcomes between the groups. **Detailed Description:** The aim of this study was to evaluate the oncological and functional outcomes in a 12-year follow-up after RALP in patients preoperatively randomized to no-MRI or MRI. Material: a total of 438 consecutive patients were referred to RALP. Of these, 222 were randomized to preoperative MRI (intervention group), and 216 were randomized to no MRI (control group). All underwent radical prostatectomy between 2010 and 2012. Study design: An experimental interventional study with 12-years follow-up Endpoints: PSA recurrence (PSA ≥0.2ng/ml) Predictors for PSA recurrence (PSM, DÁmico risk group, Gleason score, T-stage) Overall survival (OS) Predictors for OS (PSM, DÁmico risk group, Gleason score, T-stage) MRI predictors for PSM, PSA recurrence and OS Erectile function (IEEF-5) and urinary continence (IPSS-10) Urinary incontinence rates (≥1daily pads) Statistics: Before RALP, included patients were randomized to the i) non-MRI group and ii) MRI-group. Kaplan Meier curves express the RFS and OS in the two groups, and the Log-rank test assesses any difference. Cox regression analyses is used to calculate the effect of MRI (Hazard ratios with 95% CIs). Chi-square test is used to assess the difference in incontinence rates, and the Mann-Whitney U test for assessing the difference in median IIEF-5 and IPSS-10 scores. Binary and Cox regression analysis is used to assess the predictive value of a positive surgical margin on PSA recurrence, and the effect of MRI variables in predicting RFS and OS (ADC, tumor volume, and radiological T-classification). Data collection and handling of data: All patients were included in the study "Clinical impact of MRI in patients with prostate cancer." The urological and/or oncological clinic have followed these patients as part of routine clinical practice. Relevant clinical data are recorded in the "Radical prostatectomy registry ." All patients have already answered appropriate questionnaires during their regular follow-up. PhD project: The study is a PhD project for radiologist Daniyal Noor at Oslo University Hospital ### Conditions Module **Conditions:** - Prostate Cancer **Keywords:** - disease-free survival - overall survival - functional outcomes ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Patients were randomized to either MRI or no-MRI before radical prostactomy ##### Masking Info **Masking:** NONE **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 438 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** received no MRI before prostatectomy **Intervention Names:** - Diagnostic Test: Biparametric prostatic MRI **Label:** no-MRI **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** received MRI before prostatectomy **Intervention Names:** - Diagnostic Test: Biparametric prostatic MRI **Label:** MRI **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - MRI - no-MRI **Name:** Biparametric prostatic MRI **Type:** DIAGNOSTIC_TEST ### Outcomes Module #### Primary Outcomes **Description:** The difference between patients randomized to MRI or no-MRI **Measure:** Disease-free survival (DFS) **Time Frame:** 12-years after surgery #### Secondary Outcomes **Description:** The difference between patients randomized to MRI or no-MRI **Measure:** Overall survival (OS) **Time Frame:** 12-years after surgery **Description:** The difference between patients randomized to MRI or no-MRI **Measure:** Erectile dysfunction **Time Frame:** After 12 years **Description:** Predictors for recurrence **Measure:** The impact of the length of positive surgical margin and Gleason score upon DFS. **Time Frame:** After 12 years **Description:** MRI predictors for recurrence **Measure:** The impact of MRI variables for predicting PSM, PSA recurrence and OS **Time Frame:** After 12 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Prostate cancer scheduled for prostatectomy. All participated in the previous RCT Exclusion Criteria: Patients who did not sign the consent paper for any reason or did not accept the study premises. Patients who underwent MRI prior to randomization. Patents who withdrew their consent for any reason during the study. **Minimum Age:** 18 Years **Sex:** MALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Overall Officials **Official 1:** **Affiliation:** Oslo University Hospital **Name:** Erik Rud, MD,PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Rud E, Baco E, Klotz D, Rennesund K, Svindland A, Berge V, Lundeby E, Wessel N, Hoff JR, Berg RE, Diep L, Eggesbo HB, Eri LM. Does preoperative magnetic resonance imaging reduce the rate of positive surgical margins at radical prostatectomy in a randomised clinical trial? Eur Urol. 2015 Sep;68(3):487-96. doi: 10.1016/j.eururo.2015.02.039. Epub 2015 Mar 23. **PMID:** 25813692 #### See Also Links **Label:** A link to the original study **URL:** http://clinicaltrials.gov/study/NCT01347320 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000005834 - Term: Genital Neoplasms, Male - ID: D000014565 - Term: Urogenital Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000005832 - Term: Genital Diseases, Male - ID: D000091662 - Term: Genital Diseases - ID: D000091642 - Term: Urogenital Diseases - ID: D000011469 - Term: Prostatic Diseases - ID: D000052801 - Term: Male Urogenital Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M14335 - Name: Prostatic Neoplasms - Relevance: HIGH - As Found: Prostate Cancer - ID: M8946 - Name: Genital Neoplasms, Male - Relevance: LOW - As Found: Unknown - ID: M17315 - Name: Urogenital Neoplasms - Relevance: LOW - As Found: Unknown - ID: M2876 - Name: Genital Diseases - Relevance: LOW - As Found: Unknown - ID: M8944 - Name: Genital Diseases, Male - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M14333 - Name: Prostatic Diseases - Relevance: LOW - As Found: Unknown - ID: M27095 - Name: Male Urogenital Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000011471 - Term: Prostatic Neoplasms ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429865 **Brief Title:** Cytosponge in Surveillance After Endoscopic Submucosal Dissection for Esophageal Squamous Cell Carcinoma **Official Title:** Safety and Effectiveness of Cytosponge in Surveillance After Endoscopic Submucosal Dissection for Esophageal Squamous Cell Carcinoma #### Organization Study ID Info **ID:** CTSESD-20220509 #### Organization **Class:** OTHER **Full Name:** Changhai Hospital ### Status Module #### Completion Date **Date:** 2024-12 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-21 **Overall Status:** ENROLLING_BY_INVITATION #### Primary Completion Date **Date:** 2024-12 **Type:** ESTIMATED #### Start Date **Date:** 2024-05 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** Tongliao City Hospital **Class:** OTHER **Name:** Ankang Central Hospital **Class:** OTHER **Name:** Yancheng First People's Hospital **Class:** UNKNOWN **Name:** Lianshui County People's Hospital **Class:** OTHER_GOV **Name:** Nanchong Central Hospital **Class:** OTHER **Name:** Henan Provincial People's Hospital **Class:** OTHER **Name:** The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School **Class:** OTHER **Name:** Zhongda Hospital **Class:** UNKNOWN **Name:** Affiliated hospital of nanjing university hospital of Chinese medicine #### Lead Sponsor **Class:** OTHER **Name:** Changhai Hospital #### Responsible Party **Investigator Affiliation:** Changhai Hospital **Investigator Full Name:** Wangluowei **Investigator Title:** PhD; MD； Chief Physician **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** cytosponge has good diagnostic efficacy in the diagnosis of esophageal cancer, and is more safe, economic and comfortable. It is expected to replace gastroscope in the surveillance after endoscopic submucosal dissection to a certain extent. At present, there is no relevant research at home and abroad. This study plans to establish a large sample cohort based on the collaborative research network established earlier, prospectively include 1000 patients who received endoscopic submucosal dissection for esophageal squamous cell carcinoma and compare the effectiveness and safety of cytosponge and gastroscope in surveillance after endoscopic submucosal dissection for esophageal squamous cell carcinoma through self -comparison. **Detailed Description:** Esophageal cancer is one of the common malignant tumors in the world. In 2020, the number of new cases of esophageal cancer in the world will reach 604000, and the number of deaths will reach 544000. As a high incidence area of esophageal cancer in China, esophageal squamous cell carcinoma (ESCC) is the most common, with about 324000 cases of morbidity and 301000 deaths each year, posing a serious threat to people's lives and health. With the continuous development of digestive endoscopy technology, endoscopic submucosal dissection (ESD) and other minimally invasive endoscopic techniques have become the first line of treatment for early esophageal cancer. However, studies have shown that there is a risk of local recurrence within one year after ESD for early esophageal cancer, with a recurrence rate of 0-17%. Therefore, surveillance detection after ESD has become an important link in the diagnosis and treatment of esophageal cancer. At present, there is no uniform standard at home and abroad for surveillance after ESD for esophageal squamous cell carcinoma, no matter the frequency or method of surveillance. For example, the guidelines issued by Japan suggest that the surveillance should be conducted every 6 to 12 months after ESD, at least once a year. In the guidelines issued by the European Society of Gastroenterology, it is recommended to review endoscopy 3 to 6 months after ESD. If there is no recurrence, it can be changed to review endoscopy once a year. The Guidelines for the Diagnosis and Treatment of Esophageal Cancer issued by the National Health Commission in April 2022 suggests that patients should be rechecked 3 months, 6 months and 12 months after ESD, and if there is no recurrence, they should be rechecked once a year. Recheck once every three months within two years after surgery, once every six months within two to five years, and once every year after five years. Although the above guidelines and specific strategies for surveillance after esophageal cancer surgery have not yet been unified, the use of upper gastrointestinal endoscopy (hereinafter referred to as "gastroscope") as the main means of review and close surveillance are more consistent. However, due to the invasiveness, cost and availability of gastroscope, frequent endoscopic surveillance of patients with esophageal cancer after ESD may bring significant economic and health burden to patients, and lead to a decline in patients' subjective surveillance enthusiasm. Therefore, it is of great significance to find a more safe, economical and comfortable surveillance method that is equivalent to the diagnostic performance of gastroscope for standardizing the surveillance after ESD for esophageal cancer. cytosponge is a new non-invasive examination method, which can diagnose esophageal lesions by collecting esophageal cells and carrying out cytological examination and p53 staining. Its diagnostic efficacy for esophageal cancer has been confirmed in various studies at home and abroad. Esophageal cytology has been proved to have a good application prospect in the identification and screening of high-risk groups of esophageal cancer. In the 20th century, our country widely carried out esophageal mesh cytology for screening esophageal cancer in high incidence areas, but this method has low sensitivity (39%\~47%), is easy to miss diagnosis, and has poor inspection comfort, and has been eliminated at present. The improved new esophageal cell collectors (such as CytospongeTM, EsophaCapTM, Shikang No. 1 TM, etc.) adopt the expanded sponge capsule design, which increases the contact area with esophageal mucosa, and has a higher success rate than the original dragnet cytology sampling. Cytological examination is relatively simple. Combining with the high-risk factor scoring scale can improve the screening effect and improve the positive rate and screening efficiency of surveillance endoscopic intensive examination. Foreign studies on Barrett's esophagus showed that the sensitivity of cytology combined with different biomarkers of the new cell collector of the esophagus was 73.3% - 93.1%, and the specificity was 92.4-95.7%; It can play a good risk stratification role in Barrett's esophageal related dysplasia and early esophageal adenocarcinoma (0% in low-risk group, 14% in medium risk group, and 87% in high-risk group). The diagnostic and management guidelines for Barrett's esophagus formulated by the British Gastroenterological Association and the American Gastroenterological Society both point out that: Cytosponge can be used as a screening method for Barrett's esophagus, and it is more in line with the principles of health economics. As early as 2010, a prospective cohort study in the UK showed that the sensitivity and specificity of cytosponges in diagnosing Barrett's esophagus with a circumference of 1cm or more were 73.3% and 93.8%, respectively. Similarly, a multicenter randomized controlled trial in the UK in recent years also confirmed the diagnostic efficacy of cellular sponge capsule in Barrett's esophagus. In addition, for areas with high incidence of ESCC, a study based on the Golestan cohort in Iran pointed out that the accuracy of cytological examination combined with p53 staining in detecting high-grade esophageal squamous hyperplasia could reach 100%. In a previous study conducted by our team, 1844 subjects from high-risk areas of ESCC were recruited, and the effectiveness, safety and comfort of the two in esophageal cancer screening were compared through cytosponge examination and gastroscopy. The results showed that the sensitivity and specificity of cellular sponge capsule in the diagnosis of high-grade esophageal lesions (including esophageal squamous cell carcinoma and high-grade intraepithelial neoplasia) were 90% and 93.7% respectively. However, no serious adverse events were recorded during cell collection, which fully demonstrates the feasibility and safety of AI helper cytosponge in community screening of ESCC. To sum up, the cellular sponge capsule has good diagnostic efficacy in the diagnosis of esophageal cancer, and is more safe, economical and comfortable. It is expected to replace gastroscope in the surveillance after ESD to a certain extent. At present, there is no relevant research at home and abroad. This study plans to establish a large sample cohort based on the collaborative research network established earlier, prospectively include 1000 patients who received ESD resection treatment for early esophageal cancer and compare the effectiveness and safety of cytosponge and gastroscope in the surveillance of early esophageal cancer after ESD through self-comparison. ### Conditions Module **Conditions:** - Esophageal Squamous Cell Carcinoma **Keywords:** - Esophageal Squamous Cell Carcinoma - Cytosponge - Surveillance ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 1000 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants were instructed to place the capsule near the root of the tongue and fold the string in their mouths, leaving approximately 20 cm of string outside, with a blue mark on the string right at the lips. The capsule was then swallowed with water, and the end of the string was held out of the mouth. Participants were then asked to slowly drink 150-200 mL of 50°C water in approximately 2 minutes to allow the capsule to dissolve so that the sponge mesh inside was released. The device was then slowly withdrawn up the esophagus by pulling the string. The retrieved and expanded cell collection material was put in preservative fluid (Froeasy Technology, Nanjing, China) and transferred to the cytology laboratory at room temperature. **Intervention Names:** - Diagnostic Test: cytosponge **Label:** esophageal squamous cell carcinoma group **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - esophageal squamous cell carcinoma group **Description:** Use of cytosponge as a tool to patients who need surveillance after endoscopic submucosal dissection for esophageal squamous cell carcinoma **Name:** cytosponge **Type:** DIAGNOSTIC_TEST ### Outcomes Module #### Primary Outcomes **Description:** Sensitivity and Specificity **Measure:** Diagnostic accuracy **Time Frame:** 60 minute ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * (1) Sex unlimited, age 18-85; (2) The indication of ESD for early (superficial) esophageal squamous cell carcinoma conforms to the domestic and foreign guidelines; (3) The pathological stage of ESD was pT1a/pT1b. Exclusion Criteria: * (1) The pathological findings after ESD were HGIN; (2) Dysphagia (Stooler grade 2-4), inability to swallow cell sponge capsule successfully; (3) Postoperative pathological data were incomplete; (4) Have a history of cancer, early cancer, adenoma and other benign and malignant tumors of stomach and duodenum, combined with malignant tumors of other parts; (5) Previous esophageal or gastric surgery; (6) Esophagectomy, segmented endoscopic mucosal resection (EMR), multi ring mucosal resection (MBM) and other endoscopic non block resection techniques were used; (7) Those who have coagulation dysfunction or need to take anticoagulant and antiplatelet drugs continuously; (8) There are contraindications to gastroscopy and mucosal biopsy; (9) People with other serious diseases whose life expectancy is less than 5 years; (10) I refuse to cooperate with the research scheme and refuse to sign the informed consent form. **Maximum Age:** 85 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Shanghai **Country:** China **Facility:** Changhai Hospital **State:** Shanghai **Zip:** 200433 #### Overall Officials **Official 1:** **Affiliation:** Changhai Hospital **Name:** Luowei Wang, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009375 - Term: Neoplasms, Glandular and Epithelial - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000018307 - Term: Neoplasms, Squamous Cell - ID: D000004938 - Term: Esophageal Neoplasms - ID: D000005770 - Term: Gastrointestinal Neoplasms - ID: D000004067 - Term: Digestive System Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000006258 - Term: Head and Neck Neoplasms - ID: D000004066 - Term: Digestive System Diseases - ID: D000004935 - Term: Esophageal Diseases - ID: D000005767 - Term: Gastrointestinal Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M5534 - Name: Carcinoma - Relevance: HIGH - As Found: Carcinoma - ID: M5550 - Name: Carcinoma, Squamous Cell - Relevance: HIGH - As Found: Squamous Cell Carcinoma - ID: M1733 - Name: Esophageal Squamous Cell Carcinoma - Relevance: HIGH - As Found: Esophageal Squamous Cell Carcinoma - ID: M12320 - Name: Neoplasms, Glandular and Epithelial - Relevance: LOW - As Found: Unknown - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M20451 - Name: Neoplasms, Squamous Cell - Relevance: LOW - As Found: Unknown - ID: M8088 - Name: Esophageal Neoplasms - Relevance: LOW - As Found: Unknown - ID: M8886 - Name: Gastrointestinal Neoplasms - Relevance: LOW - As Found: Unknown - ID: M7256 - Name: Digestive System Neoplasms - Relevance: LOW - As Found: Unknown - ID: M9348 - Name: Head and Neck Neoplasms - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M8085 - Name: Esophageal Diseases - Relevance: LOW - As Found: Unknown - ID: T2141 - Name: Esophageal Cancer - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002277 - Term: Carcinoma - ID: D000002294 - Term: Carcinoma, Squamous Cell - ID: D000077277 - Term: Esophageal Squamous Cell Carcinoma ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429852 **Brief Title:** Efficacy, Feasibility, and Acceptability of the DeST-ACT: Trauma-Focused Acceptance and Commitment Therapy Program **Official Title:** Examining the Efficacy, Feasibility, and Acceptability of the DeST-ACT: Trauma-Focused Acceptance and Commitment Therapy Program on Life Satisfaction in Earthquake Survivors #### Organization Study ID Info **ID:** CSV202403 #### Organization **Class:** OTHER **Full Name:** CanSagligi Foundation ### Status Module #### Completion Date **Date:** 2024-10 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-06-04 **Type:** ACTUAL **Last Update Submit Date:** 2024-06-03 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2024-10 **Type:** ESTIMATED #### Start Date **Date:** 2024-06 **Type:** ESTIMATED **Status Verified Date:** 2024-06 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** CanSagligi Foundation #### Responsible Party **Investigator Affiliation:** CanSagligi Foundation **Investigator Full Name:** Sevinc Ulusoy **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The aim of this study is to develop a post-earthquake, trauma-focused Acceptance and Commitment Therapy (ACT)-based psychosocial intervention program (DeST-ACT) and to examine its effectiveness, feasibility, and acceptability of this program in enhancing life satisfaction and psychological flexibility in individuals exposed to earthquake trauma. In this regard, the main hypothesis is that the DeST-ACT psychosocial intervention program is effective, feasible, and acceptable among individuals exposed to earthquake trauma, including both primary and secondary outcomes of the program. **Detailed Description:** This quantitative, randomized controlled trial involves two groups and includes a pre-test and repeated post-tests. The study aims to assess the effectiveness, feasibility, and acceptability of the developed DeST-ACT program in addressing post-traumatic stress disorder, psychological flexibility, life satisfaction, values-based living, and depression-anxiety-stress levels in individuals affected by the February 6, 2023 earthquake. Participants will be randomly assigned to experimental and control groups in a 1:1 ratio using an internet-based block randomization program. The DeST-ACT psychosocial intervention program consists of a 4-session online intervention supported by self-help materials. Each session in the 4-week program is held once a week for 50 minutes. The main hypotheses are: * The intervention group will demonstrate a significant decrease in Post Traumatic Stress Disorder (PTSD) and depression-anxiety-stress levels compared to the control group. * The intervention group will experience a greater increase in values-based living, life satisfaction, and psychological flexibility over time compared to the control group. * The intervention group will demonstrate a significant decrease in PTSD and depression-anxiety-stress levels compared to baseline measures. * The intervention group will experience a greater increase in values-based living, life satisfaction, and psychological flexibility over time compared to baseline measures. ### Conditions Module **Conditions:** - Trauma and Stressor Related Disorders ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** The study will be a quantitative, randomized controlled trial with two groups, including a pre-test and repeated post-tests. ##### Masking Info **Masking:** NONE **Masking Description:** Randomization will be conducted by a research assistant using an internet-based program following the pre-test. The pre-test and post-tests will be administered by a different researcher who is blinded to the study. The therapy program will be conducted by independent therapists who are also blinded to the study. **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 40 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants in the intervention group will undergo the DeST-ACT psychosocial intervention. This program includes a 4-session online intervention supplemented with self-help materials. These materials comprise concise texts designed to reinforce the skills covered in each session. **Intervention Names:** - Behavioral: The DeST-ACT Trauma-Focused Acceptance and Commitment Therapy Program **Label:** DeST-ACT Intervention Group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** The other group will consist of participants on the wait-list. Similar to those in the intervention group, participants in the waitlist group will undergo research assessments at baseline, post-therapy, and 1 month after therapy. Subsequently, they will be included in the 4-session intervention program. No measurements will be taken after the intervention. **Label:** Waitlist Group **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - DeST-ACT Intervention Group **Description:** The Trauma-focused psychosocial intervention program consists of 4 sessions online therapy. **Name:** The DeST-ACT Trauma-Focused Acceptance and Commitment Therapy Program **Type:** BEHAVIORAL ### Outcomes Module #### Other Outcomes **Description:** Caps-5 is a structured clinical interview form developed to assess PTSD symptoms and symptom severity. The CAPS-5 consists of questions that assess the frequency and severity of each symptom, the impact of the symptoms on the patient's social and occupational functioning, and the total severity of symptoms. Turkish validity and reliability study was conducted and Cronbach's Alpha values were higher than 0.87 for all symptom dimensions. **Measure:** Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders-5 (CAPS-5) **Time Frame:** The scale will be used to assess the inclusion criterion before the randomization. #### Primary Outcomes **Description:** The PCL-5 was developed based on the diagnostic criteria in the Diagnostic and Statistical Manual of Mental Disorders-5, and its aim is to evaluate PTSD symptoms. The scale consists of 20 items rated on a 5-point Likert scale. Scores above 47 are indicative of PTSD. **Measure:** PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders-5 (PCL-5) **Time Frame:** At baseline, after 4 weeks, after 8 weeks **Description:** The DASS-21 measures the dimensions of depression, stress, and anxiety. The scale consists of 21 items rated on a 4-point Likert scale ranging from 0 (Never) to 4 (Always) with scores ranging from a minimum of 0 to a maximum of 84. The Cronbach's alpha values for the scale, based on Turkish validity and reliability studies, are 0.80 for anxiety, 0.82 for depression, and 0.75 for stress. **Measure:** Depression Anxiety and Stress Scale 21 (DASS-21) **Time Frame:** At baseline, after 4 weeks, after 8 weeks **Description:** The Engaged Living Scale is designed to evaluate values-based living. It consists of 16 items rated on a 5-point Likert scale, ranging from 1 (Totally Agree) to 5 (Totally Disagree), with scores ranging from a minimum of 16 to a maximum of 80. The scale, for which Turkish validity and reliability studies have been conducted, has two sub-dimensions: "valued living" and "life fulfillment." The Cronbach's alpha value for the Turkish version of the scale is 0.91, with 0.87 for the valued living sub-dimension and 0.86 for the life fulfillment sub-dimension. **Measure:** Engaged Living Scale **Time Frame:** At baseline, after 4 weeks, after 8 weeks #### Secondary Outcomes **Description:** The AAQ-2 is a measure designed to evaluate experiential avoidance. The scale consists of 7 items rated on a 7-point Likert scale, with scores ranging from a minimum of 7 to a maximum of 49. Higher scores indicate greater experiential avoidance. **Measure:** Acceptance and Action Questionnaire-2 (AAQ-2) **Time Frame:** At baseline, after 4 weeks, after 8 weeks **Description:** It is a semi-structured form designed by the researchers to assess acceptability and perceived effectiveness. The form consists of 10 questions, each scored on a scale from 0 (not at all) to 4 (completely). **Measure:** Therapy Satisfaction Questionnaire **Time Frame:** after 4 week **Description:** To evaluate acceptability, participants' attendance rates to the program will be recorded. **Measure:** Drop Rate **Time Frame:** after 8 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Volunteering to participate in the research * Being present in cities such as Kahramanmaras, Gaziantep, Hatay, Adiyaman, or Malatya during the earthquake on February 6, where destruction occurred * Being literate * Being able to have an online interview with the therapist * Having sub-threshold PTSD or PTSD Exclusion Criteria: * Being in other cities at the time of the earthquake and not being exposed to the earthquake * Having visual and/or hearing problems * Having any psychotic disorder, experiencing an active mood episode, or having conditions such as intellectual disability or dementia that would prevent participation in therapy * Starting a new psychiatric treatment during the research period or having a change in medication or dosage within the last 3 months. **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Aleyna Güleryüz, BA **Phone:** 02122696611 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Sevinç Ulusoy, MD **Role:** CONTACT #### Locations **Location 1:** **City:** Istanbul **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Eda Aksoy - **Role:** CONTACT ***Contact 2:*** - **Name:** Sevinç Ulusoy, MD - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 3:*** - **Name:** Aleyna Güleryüz, BA - **Role:** SUB_INVESTIGATOR **Country:** Turkey **Facility:** Cansagligi Foundation Center for Contextual Behavioral Science **State:** Uskudar ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001523 - Term: Mental Disorders ### Condition Browse Module - Browse Branches - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions - Abbrev: BXM - Name: Behaviors and Mental Disorders ### Condition Browse Module - Browse Leaves - ID: M17685 - Name: Wounds and Injuries - Relevance: HIGH - As Found: Trauma - ID: M222 - Name: Trauma and Stressor Related Disorders - Relevance: HIGH - As Found: Trauma and Stressor Related Disorders - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000014947 - Term: Wounds and Injuries - ID: D000068099 - Term: Trauma and Stressor Related Disorders ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429839 **Brief Title:** Nimotuzumab Concurrent With Chemoradiotherapy for Esophageal Cancer Patients **Official Title:** Nimotuzumab Concurrent With Chemoradiotherapy for Elderly or Malnourished Patients With Unresectable Esophageal Squamous Cell Carcinoma: A Phase II Study #### Organization Study ID Info **ID:** NCC4571 #### Organization **Class:** OTHER **Full Name:** Cancer Institute and Hospital, Chinese Academy of Medical Sciences ### Status Module #### Completion Date **Date:** 2026-12-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-21 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2025-12-31 **Type:** ESTIMATED #### Start Date **Date:** 2023-03-01 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-13 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Cancer Institute and Hospital, Chinese Academy of Medical Sciences #### Responsible Party **Investigator Affiliation:** Cancer Institute and Hospital, Chinese Academy of Medical Sciences **Investigator Full Name:** XIN WANG **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Elderly or malnourished patients diagnosed with locally advanced esophageal squamous cell carcinoma (ESCC) had poor prognosis. Radiotherpy was an important and effective treatment in treating ESCC. The present study is a one-arm trial that seeks to evaluate the efficacy in patients with unresectable ESCC. The study objectives include R0 resection rate, complete pathological response and treatment toxicity, etc. Nimotuzumab is a recombinant humanized monoclonal antibody against EGFR. Its efficacy and safety in patients with esophageal cancer have been confirmed by many studies. The current prospective phase II study aimed to evaluate the efficacy and safety of a combination regimen comprising chemotherapy with nimotuzumab with a dose of 800mg per week and S-1 and concurrent radiotherapy for patients who are elderly or malnourished. ### Conditions Module **Conditions:** - Esophageal Cancer - Nimotuzumab - Chemoradiotherapy - Chemotherapy - Immunotherapy ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 55 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Combination Product: Nimotuzumab with chemoradiotherapy **Label:** Nimotuzumab concurrent with chemordiotherapy followed by surgery **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Nimotuzumab concurrent with chemordiotherapy followed by surgery **Description:** Radiotherapy,40-50.4Gy/20-28f. Nimotuzumab 400mg,ivgtt,W2d. Chemotherapy, S-1,40-60mg/m2, on BSA, orally twice daily on radiotherapy days. **Name:** Nimotuzumab with chemoradiotherapy **Type:** COMBINATION_PRODUCT ### Outcomes Module #### Primary Outcomes **Description:** Minimal distance tumor/circumferential resection margin (CRM) \> 1 mm. **Measure:** R0 resection rate **Time Frame:** 4 months after initiation of induction chemoimmunotherapy #### Secondary Outcomes **Description:** the complete remission of all viable cancer cells in any of the specimens from surgery, including the primary site and lymph nodes **Measure:** Pathological complete response **Time Frame:** 4 months after initiation of induction chemoimmunotherapy **Description:** the time from start of chemoradiotherapy to 1 month after chemoradiotherapy **Measure:** Event-free survival **Time Frame:** 1 month after chemoradiotherapy **Measure:** Postoperative complications **Time Frame:** 1 month after surgery **Description:** the time from start of induction chemo(immuno)therapy to all-cause death, or the last day of follow-up **Measure:** Overall survival **Time Frame:** 1 year after all treatment ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Histologically confirmed esophageal squamous cell carcinoma. * No previous treatment for the esophageal carcinoma. * KPS score ≥70. * NRS-2002 score≥2. * Main organs and bone marrow function are normal: routine blood tests: hemoglobin (Hb) ≥100g/L ; absolute neutrophil count (NEUT)≥1.5×109/L; platelets (PLT) ≥100×109/L; white blood cell (WBC)≥3.5×109/L,biochemical examination: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤1.5×UNL; serum total bilirubin (TBIL) ≤1.5×UNL; serum creatinine ( Cr) 1.0×1.5UNL, and BUN≤1.0×UNL; Exclusion Criteria: * Previous treatment of the esophageal cancer with surgery, radiation, or chemotherapy. * Those combined with other primary malignant tumors other than esophageal cancer (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix); * At the time of diagnosis, there were distant and hematogenous metastases beyond the supraclavicular lymph node region, including retroperitoneal multiple lymph node metastasis, bone metastasis, brain metastasis, lung metastasis, liver metastasis, malignant pleural effusion and ascites * There are active infections, such as active tuberculosis and hepatitis * There are contraindications to targeted therapy. **Maximum Age:** 80 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Xin Wang, Doctor **Phone:** 13311583220 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Guojie Feng, B.M **Phone:** 16601212285 **Role:** CONTACT #### Locations **Location 1:** **City:** Beijing **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Xin Wang, Doctor - **Phone:** 13311583220 - **Role:** CONTACT **Country:** China **Facility:** National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College **Status:** RECRUITING ## Derived Section ### Condition Browse Module - Ancestors - ID: D000005770 - Term: Gastrointestinal Neoplasms - ID: D000004067 - Term: Digestive System Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000006258 - Term: Head and Neck Neoplasms - ID: D000004066 - Term: Digestive System Diseases - ID: D000004935 - Term: Esophageal Diseases - ID: D000005767 - Term: Gastrointestinal Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M5534 - Name: Carcinoma - Relevance: LOW - As Found: Unknown - ID: M5550 - Name: Carcinoma, Squamous Cell - Relevance: LOW - As Found: Unknown - ID: M1733 - Name: Esophageal Squamous Cell Carcinoma - Relevance: LOW - As Found: Unknown - ID: M8088 - Name: Esophageal Neoplasms - Relevance: HIGH - As Found: Esophageal Cancer - ID: M25306 - Name: Malnutrition - Relevance: LOW - As Found: Unknown - ID: M8886 - Name: Gastrointestinal Neoplasms - Relevance: LOW - As Found: Unknown - ID: M7256 - Name: Digestive System Neoplasms - Relevance: LOW - As Found: Unknown - ID: M9348 - Name: Head and Neck Neoplasms - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M8085 - Name: Esophageal Diseases - Relevance: LOW - As Found: Unknown - ID: T2141 - Name: Esophageal Cancer - Relevance: HIGH - As Found: Esophageal Cancer ### Condition Browse Module - Meshes - ID: D000004938 - Term: Esophageal Neoplasms ### Intervention Browse Module - Ancestors - ID: D000074322 - Term: Antineoplastic Agents, Immunological - ID: D000000970 - Term: Antineoplastic Agents ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M288889 - Name: Nimotuzumab - Relevance: HIGH - As Found: Details - ID: M1346 - Name: Antineoplastic Agents, Immunological - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000501466 - Term: Nimotuzumab ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429826 **Brief Title:** [Trial of device that is not approved or cleared by the U.S. FDA] **Official Title:** [Trial of device that is not approved or cleared by the U.S. FDA] #### Organization Study ID Info **ID:** ATTN201-P3-01 #### Organization **Full Name:** [Redacted] ### Status Module **Delayed Posting:** True #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-21 **Overall Status:** WITHHELD #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Lead Sponsor **Name:** [Redacted] #### Responsible Party **Old Name Title:** [Redacted] **Old Organization:** [Redacted] ## Derived Section ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429813 **Brief Title:** Remotely Monitored Exercise Interventions in Patients With mCSPC Undergoing ADT (Prostate 006) **Official Title:** A Feasibility Study to Examine the Impact of Remotely Monitored Exercise Interventions on Cardiorespiratory/Muscular Fitness and Fatigue in Patients With Metastatic Castrate-sensitive Prostate Cancer (mCSPC) Undergoing Treatment With Androgen-deprivation Therapy (ADT) Intensification #### Organization Study ID Info **ID:** HSR230542 #### Organization **Class:** OTHER **Full Name:** University of Virginia ### Status Module #### Completion Date **Date:** 2025-11 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-23 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2025-11 **Type:** ESTIMATED #### Start Date **Date:** 2024-07 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-14 **Study First Submit QC Date:** 2024-05-23 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Paul Viscuse #### Responsible Party **Investigator Affiliation:** University of Virginia **Investigator Full Name:** Paul Viscuse **Investigator Title:** Assistant Professor **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** This study consists of two home-based exercise programs: a stationary exercise bicycle intervention (Arm A), and a walking intervention (Arm B). The study will enroll 24 patients who are starting ADT (Androgen Deprivation Therapy)/ARSI (Androgen-Receptor Signaling Inhibitors) therapy for newly diagnosed metastatic castrate-sensitive prostate cancer (mCSPC). All participants will be asked to complete 1-2 training sessions at UVA prior to starting the exercise. All participants will be asked to complete aerobic and strength testing before and after the exercise program. Participants will be asked to answer questionnaires throughout the program. The at-home exercise will last for 12 weeks. **Detailed Description:** The purpose of this study is to find out how many patients who are being treated for mCSPC complete one of two home-based exercise programs. The researchers want to find out how much exercise participants complete and how satisfied they are with the program. Another purpose of this study is to learn if doing the exercise changes fitness levels and/or muscle strength, and what relationship those changes might have on feeling tired during cancer treatment. Participants will be randomly assigned (like the flip of a coin) to one of two home-based exercise programs: * Arm A: A high intensity interval (HIIT) stationary bike program * Arm B: A walking program Participants in the cycling group (Arm A) will receive a stationary exercise bike for home exercise. All participants in the study (Arms A and B) will receive an activity monitor (watch) and a heart rate-monitoring chest strap that sends information back to the study team. Participants will receive 1-2 exercise training sessions, held in a UVA research lab, to allow them to experience the level of the exercise they will be asked to complete. Each participant will make a personal plan with the study team to gradually workup to the exercise goal assigned to each group. The research team will answer any questions and help set up the activity monitors. After these session(s), the remaining 12 weeks of exercise will occur at home. ### Conditions Module **Conditions:** - Castrate Sensitive Prostate Cancer - Metastatic Prostate Cancer **Keywords:** - prostate - metastatic prostate cancer - metastatic castrate-sensitive prostate cancer - prostate cancer - exercise - ADT - ARSI ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 24 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** HIIT Cycling Intervention **Intervention Names:** - Behavioral: Home-Based Exercise Intervention - HIIT Cycling **Label:** Arm A **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Walking Intervention **Intervention Names:** - Behavioral: Home-Based Exercise Intervention - Walking **Label:** Arm B **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Arm B **Description:** 30 minutes of walking or light jogging a day at a moderate intensity for 30 minutes a day, 5 days a week for 12 weeks **Name:** Home-Based Exercise Intervention - Walking **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - Arm A **Description:** Four, 4 minute high intensity intervals of exercise, separated by 3 minutes of lower intensity exercise + a 10 minute warm up and 5 minute cool down for 40 minutes a day, 3 days a week for 12 weeks **Name:** Home-Based Exercise Intervention - HIIT Cycling **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** Percentage of participants who complete the post-intervention follow-up assessment **Measure:** Number of participants who complete the post-intervention follow-up assessment **Time Frame:** 14 weeks from the start of the intervention #### Secondary Outcomes **Description:** Frequency, intensity and duration of exercise as measured by the activity monitors. **Measure:** Treatment engagement with intervention **Time Frame:** From the beginning of the intervention to the Post-intervention visit (about 12 weeks) **Description:** The Physical Activity Enjoyment Scale (PACES) is an 18 question, 7 point scale that includes questions regarding enjoyment of physical activity in the study. **Measure:** Acceptability of exercise **Time Frame:** From the beginning of the intervention to the Post-intervention visit (about 12 weeks) **Description:** Exit interviews include open and closed ended questions about the participant's experience in the study. **Measure:** Patient-reported outcomes on exercise **Time Frame:** From the beginning of the intervention to the Post-intervention visit (about 12 weeks) **Description:** Number of individuals screened and randomized **Measure:** Rate of recruitment per month **Time Frame:** Each month for 12 months (estimated duration of accrual of participants) **Description:** As measured by VO2 peak **Measure:** Physical fitness (Cardiorespiratory) **Time Frame:** Measured at the baseline visit before the start of the intervention and post-intervention visit (about 16 weeks later) **Description:** Isometric and isokinetic torque in multiple positions (e.g. 60-120 degrees) **Measure:** Muscular strength (quadriceps) **Time Frame:** Measured at the baseline visit before the start of the intervention and post-intervention visit (about 16 weeks later ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Provision of signed and dated informed consent form 2. Stated willingness to comply with all study procedures and availability for the duration of the study 3. Male, aged ≥18 years old 4. Diagnosis of mCSPC (defined as either biopsy-proven metastatic prostate cancer or elevated PSA (Prostate Specific Antigen) in the setting of imaging findings typical of prostate cancer spread; patients can either have de novo metastatic disease or recurrent metastatic disease after prior definitive therapy to the primary tumor with either surgery or radiation) 5. Planned treatment with ADT (LHRH \[Luteinizing hormone-releasing hormone\] agonist such as leuprolide or LHRH antagonist such as degarelix), and intensification with ARSI (abiraterone/prednisone, enzalutamide, apalutamide, or darolutamide) 6. Oncologist clearance for exercise training after taking into account functional status and co-morbid conditions that may limit ability to participate. 7. Ability to take oral medication and willing to adhere to the study intervention regimen 8. Ability to read, speak, and understand English. Exclusion Criteria: 1. Castrate-resistant prostate cancer (defined as prostate cancer previously treated with a backbone of ADT hormonal therapy with either progression of disease on imaging PSA progression with PSA increase of \> 25% and 2 ng/mL above nadir, confirmed at 2 time points at least 3 weeks apart, in the setting of testosterone level \< 50) 2. Patients with prostate cancer with biochemical recurrence (e.g., received prior definitive therapy with subsequent PSA \[Prostate-Specific Antigen\] rise) but radiographic imaging is negative for metastatic disease 3. Metastatic bone lesion(s) in the proximal femur, bone lesion causing impending fracture, or other metastatic site deemed unsafe for walking by treating physician 4. Medical/orthopedic comorbidities that preclude stationary cycling or walking 5. Significant cardiac/renal/hepatic/hematological/pulmonary disease precluding exercise training 6. Unstable angina or myocardial infarction within 4-weeks prior to treatment 7. Complex ventricular arrhythmias or New York Heart Association class IV symptoms 8. Symptomatic severe aortic stenosis 9. Acute pulmonary embolus 10. Acute myocarditis 11. Untreated high-risk proliferative retinopathy 12. Recent retinal hemorrhage 13. Uncontrolled hypertension (systolic blood pressure \> 180 mm Hg or diastolic blood pressure \> 120 mm Hg) 14. Severe baseline electrolyte abnormalities (e.g. potassium) that may predispose patient to arrhythmias in the opinion of the treating investigator 15. Uncontrolled metabolic disease (diabetes with fasting blood sugar \>300 mg/dl, thyrotoxicosis, myxedema) 16. Symptomatic peripheral vascular disease 17. Prior treatment with taxane- or platinum- based chemotherapy 18. Prior treatment with PARP \[Poly (ADP-ribose) polymerase\] inhibitors 19. Prior treatment with radium-223 or lutetium-177 **Minimum Age:** 18 Years **Sex:** MALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Steven Goff **Phone:** 434-806-1357 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Christine Martin **Role:** CONTACT #### Locations **Location 1:** **City:** Charlottesville **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Steven Goff - **Phone:** 434-806-1357 - **Role:** CONTACT **Country:** United States **Facility:** University of Virginia **State:** Virginia **Zip:** 22908 #### Overall Officials **Official 1:** **Affiliation:** University of Virginia **Name:** Paul Viscuse, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000005834 - Term: Genital Neoplasms, Male - ID: D000014565 - Term: Urogenital Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000005832 - Term: Genital Diseases, Male - ID: D000091662 - Term: Genital Diseases - ID: D000091642 - Term: Urogenital Diseases - ID: D000011469 - Term: Prostatic Diseases - ID: D000052801 - Term: Male Urogenital Diseases - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: All - Name: All Conditions - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M14335 - Name: Prostatic Neoplasms - Relevance: HIGH - As Found: Prostate Cancer - ID: M10018 - Name: Hypersensitivity - Relevance: HIGH - As Found: Sensitive - ID: M8364 - Name: Fatigue - Relevance: LOW - As Found: Unknown - ID: M8946 - Name: Genital Neoplasms, Male - Relevance: LOW - As Found: Unknown - ID: M17315 - Name: Urogenital Neoplasms - Relevance: LOW - As Found: Unknown - ID: M2876 - Name: Genital Diseases - Relevance: LOW - As Found: Unknown - ID: M8944 - Name: Genital Diseases, Male - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M14333 - Name: Prostatic Diseases - Relevance: LOW - As Found: Unknown - ID: M27095 - Name: Male Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000011471 - Term: Prostatic Neoplasms - ID: D000006967 - Term: Hypersensitivity ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M4059 - Name: Androgens - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429800 **Brief Title:** A Study to Evaluate the Safety and Preliminary Efficacy of ATA3219 in Participants With Lupus Nephritis **Official Title:** A Phase 1 Study to Evaluate the Safety and Preliminary Efficacy of ATA3219, Allogeneic Anti-CD19 Chimeric Antigen Receptor T-cell (CAR T) Therapy, in Subjects With Lupus Nephritis #### Organization Study ID Info **ID:** ATA3219-AEC-104 #### Organization **Class:** INDUSTRY **Full Name:** Atara Biotherapeutics ### Status Module #### Completion Date **Date:** 2029-04 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-21 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2027-10 **Type:** ESTIMATED #### Start Date **Date:** 2024-10-31 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Atara Biotherapeutics #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Oversight Has DMC:** True ### Description Module **Brief Summary:** The purpose of the study is to evaluate the safety and preliminary efficacy of ATA3219 (following lymphodepletion) for treatment of participants with lupus nephritis (LN). **Detailed Description:** This is a Phase 1, multi-centered, open-labeled, dose escalation study to evaluate the safety and preliminary efficacy of ATA3219 (as monotherapy) in participants with LN. Up to 3 dose levels (DLs) will be explored in the dose escalation portion of the study and if needed a lower dose may be explored. Prior to undergoing any screening procedure, prospective participants must undergo the ATA3219 inventory check assessments to ensure availability of an appropriate partially human leukocyte antigen (HLA)-matched ATA3219 lot. Before administration of ATA3219, participants will receive conditioning chemotherapy. For all enrolled participants, hospitalization during and following ATA3219 dosing is mandatory. Participants will receive a single dose intravenous (IV) infusion of ATA3219 (monotherapy) on Day 1. Participants will remain inpatient for a minimum of 1 week post ATA3219 dosing, where they will be frequently monitored. Lupus nephritis activity will be assessed by the investigator on Day 28 (+ 5 days) following each dose of ATA3219. During dose escalation, up to 3 dose levels of ATA3219 are planned to be evaluated sequentially and a lower dose may be added. At least 3 and up to 6 dose-limiting toxicity (DLT)-evaluable participants, those who complete the 28-day DLT observation period, will be assessed at each dose level. Within each dose level, treatment will be staggered to allow appropriate safety monitoring by an independent Data Safety Monitoring Committee (DSMC). Participants who do not receive ATA3219 for any cause may be replaced. Participants who experience an adverse event (AE) prior to completion of the 28-day DLT observation period will not be replaced. If a participant is treated with ATA3219 and discontinues for any reason other than a DLT prior to completing the 28-day DLT observation period, an additional participant may be enrolled at the dose level to ensure that the recommended phase 2 dose (RP2D) can be determined. In rare situations, retreatment of participants with inadequate renal response may be considered. After treatment is completed or discontinued, participants will be followed for safety and renal response for up to 24 months from the last dose of ATA3219. A separate long-term follow-up study will be conducted to follow participants for up to a total of 15 years after their last dose of ATA3219. ### Conditions Module **Conditions:** - Lupus Nephritis - Systemic Lupus Erythematosus **Keywords:** - Lupus Nephritis (LN) - Systemic Lupus Erythematosus (SLE) - Anti CD19 Chimeric Antigen Receptor T cell (CAR T) Therapy - Human leukocyte antigen (HLA) - Epstein-Barr virus (EBV) T cells ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** SEQUENTIAL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 26 **Type:** ESTIMATED **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants will receive a single IV infusion of ATA3219 Dose Level -1 (if required) on Day 1 of a 28-day dose limiting toxicity (DLT) observation period. **Intervention Names:** - Drug: ATA3219 **Label:** ATA3219 Dose Level -1 **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Participants will receive a single IV infusion of ATA3219 Dose Level 1 on Day 1 of a 28-day DLT observation period. **Intervention Names:** - Drug: ATA3219 **Label:** ATA3219 Dose Level 1 **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Participants will receive a single IV infusion of ATA3219 Dose Level 2 on Day 1 of a 28-day DLT observation period. **Intervention Names:** - Drug: ATA3219 **Label:** ATA3219 Dose Level 2 **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** Participants will receive a single IV infusion of ATA3219 Dose Level 3 on Day 1 of a 28-day DLT observation period. **Intervention Names:** - Drug: ATA3219 **Label:** ATA3219 Dose Level 3 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - ATA3219 Dose Level -1 - ATA3219 Dose Level 1 - ATA3219 Dose Level 2 - ATA3219 Dose Level 3 **Description:** ATA3219 is an allogeneic chimeric antigen receptor (CAR) T-cell therapy containing a second generation CD19 CAR construct in Epstein Barr virus (EBV) T cells, administered intravenously on Day 1. **Name:** ATA3219 **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Incidence and severity of treatment-emergent adverse events, including adverse events of special interest **Time Frame:** From administration of conditioning treatment through 90 days after administration of study drug **Measure:** Incidence of Dose-limiting Toxicities **Time Frame:** Day 1 through Day 28 of first dose of study drug **Measure:** Maximum Tolerated dose **Time Frame:** Day 1 through Day 28 of first dose of study drug **Measure:** Recommended Phase 2 dose of ATA3219 **Time Frame:** Day 1 through Day 28 of first dose of study drug #### Secondary Outcomes **Measure:** Maximum Observed Plasma Concentration (Cmax) of ATA3219 **Time Frame:** Pre-dose on Day 1 through 24 months after the last dose on a defined schedule **Measure:** Time to Reach Cmax (Tmax) of ATA3219 **Time Frame:** Pre-dose on Day 1 through 24 months after the last dose on a defined schedule **Measure:** Partial Area Under the Curve (pAUC) of ATA3219 **Time Frame:** Pre-dose on Day 1 through 24 months after the last dose on a defined schedule **Measure:** Last Observed Plasma Concentration (Clast) of ATA3219 **Time Frame:** Pre-dose on Day 1 through 24 months after the last dose on a defined schedule **Measure:** Time of Clast of ATA3219 **Time Frame:** Pre-dose on Day 1 through 24 months after the last dose on a defined schedule **Measure:** Terminal Half-life (t1/2) of ATA3219 **Time Frame:** Pre-dose on Day 1 through 24 months after the last dose on a defined schedule **Measure:** Complete Renal Response **Time Frame:** Weeks 24 and 52 **Measure:** Partial Renal Response **Time Frame:** Weeks 24 and 52 **Measure:** Renal Objective Response Rate **Time Frame:** Weeks 24 and 52 **Measure:** Change From Baseline in Urine protein to Creatinine Ratio **Time Frame:** Baseline (Day -5) through 24 months after the last dose on a defined schedule **Measure:** Change From Baseline in Estimated Glomerular Filtration Rate **Time Frame:** Baseline (Day -5) through 24 months after the last dose on a defined schedule **Measure:** Duration of Urine Protein to Creatinine ratio ≤ 0.5 **Time Frame:** Baseline (Day -5) through 24 months after the last dose on a defined schedule **Measure:** Change From Baseline in Lupus Low Disease Activity State (LLDAS) **Time Frame:** Baseline (Day 28) through 24 months after the last dose on a defined schedule **Measure:** Change From Baseline in Definition of Remission in Systemic Lupus Nephritis (DORIS) **Time Frame:** Baseline (Day 28) through 24 months after the last dose on a defined schedule **Measure:** Change From Baseline in the Modified Version of the Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Nephritis Disease Activity (Hybrid SELENA-SLEDAI) Index **Time Frame:** Baseline (Day 28) through 24 months after the last dose on a defined schedule **Measure:** Change From Baseline in British Isles Lupus Assessment Group (BILAG) Index **Time Frame:** Baseline (Day 28) through 24 months after the last dose on a defined schedule **Measure:** Change From Baseline in Antibodies to Double Stranded Deoxyribonucleic Acid **Time Frame:** Baseline (Day 1) through 24 months after the last dose on a defined schedule **Measure:** Change From Baseline in Complement Component 3 (C3) and Complement Component 4 (C4) Levels **Time Frame:** Baseline (Day 1) through 24 months after the last dose on a defined schedule ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Diagnosed with SLE according to the 2019 European League Against Rheumatism/American College of Rheumatology classification for SLE or the Systemic Lupus International Collaborating Clinics Classification criteria \[Petri 2012\]. 2. Meets one or more of the following immunologic criteria during screening: 1. Anti double stranded DNA above laboratory reference range, except enzyme linked immunosorbent assay (2 × above laboratory reference range), OR 2. Presence of anti-Smith antibody, OR 3. Low complement as demonstrated by low complement component 3, low complement component 4, or low complement CH50. 3. History of International Society of Nephrology/Renal Pathology Society (ISN/RPS) Class III or IV with or without Class V glomerulonephritis on renal biopsy either within 6 months prior to screening or as performed during screening. Biopsy should demonstrate evidence of active nephritis. 4. Proteinuria level between ≥ 1.0 to 6.0 g/day via urine protein creatinine ratio during screening. 5. Has refractory LN defined as having received 1 or more standard therapies for LN (which must have included mycophenolate mofetil, mycophenolic acid, or cyclophosphamide), and: 1. Has worsening LN (per criteria listed in \[Gordon 2009\]) while on treatment, OR 2. Has not achieved a complete renal response (CRR) after 2 or more lines of therapy, OR 3. Has not achieved a CRR after first-line therapy after a minimum of 12 months. 6. Is using a stable, optimized dose of a renin angiotensin system inhibitor for at least 4 weeks prior to enrollment, unless deemed inappropriate by the investigator. 7. Participants must have been previously vaccinated for pneumococcus within 5 years prior to screening (and no later than 4 weeks prior to enrollment) or be willing to receive prophylaxis against infections with encapsulated bacteria via vaccination in accordance with local standards of practice and/or guidelines. 8. Is current per national or local health authority or institutional guidelines for immunocompromised individuals on the following vaccinations, unless refused or medically contraindicated: varicella zoster (Shingrix), pneumococcal, influenza, and Corona virus disease 2019 (COVID-19). Exclusion Criteria: 1. Severe kidney disease as assessed locally, defined as history of ISN/RPS Class VI or isolated Class V glomerulonephritis (without co existent/predominant Class III or IV glomerulonephritis) on renal biopsy. 2. Has a concurrent systemic autoimmune disease that may confound study assessments other than SLE, LN, or cutaneous lupus erythematosus. 3. Has any unstable or progressive manifestation of SLE that is likely to warrant an intensification of lupus-directed therapy 4. Has a history of confirmed or suspected drug-induced lupus. 5. Has a history of catastrophic antiphospholipid syndrome, or any history of prior thrombosis due to antiphospholipid syndrome resulting in hospitalization due to myocardial infarction, pulmonary embolism, or stroke. 6. Has a history of bleeding disorder requiring hospitalization or systemic therapeutic intervention within the previous 3 months, or for participants without a prior kidney biopsy meeting eligibility criterion within the past 6 months who will require a biopsy during screening, any contraindication to kidney biopsy. 7. Severe B cell immunodeficiency as evidenced by clinically significant refractory/recurrent infection. 8. Any prior cellular therapies, obinutuzumab, anti-cluster of differentiation 19 (CD19) antibody, or B-cell targeting bispecific antibody, unless B-cells have recovered to baseline as assessed by the investigator. Investigational therapies or initiation of new SLE-directed therapies within 4 weeks. **Maximum Age:** 55 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Study Director **Phone:** 650-278-8930 **Phone Ext:** 1 **Role:** CONTACT #### Overall Officials **Official 1:** **Affiliation:** Atara Biotherapeutics **Name:** Justin Walstrom, MD **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Petri M, Orbai AM, Alarcon GS, Gordon C, Merrill JT, Fortin PR, Bruce IN, Isenberg D, Wallace DJ, Nived O, Sturfelt G, Ramsey-Goldman R, Bae SC, Hanly JG, Sanchez-Guerrero J, Clarke A, Aranow C, Manzi S, Urowitz M, Gladman D, Kalunian K, Costner M, Werth VP, Zoma A, Bernatsky S, Ruiz-Irastorza G, Khamashta MA, Jacobsen S, Buyon JP, Maddison P, Dooley MA, van Vollenhoven RF, Ginzler E, Stoll T, Peschken C, Jorizzo JL, Callen JP, Lim SS, Fessler BJ, Inanc M, Kamen DL, Rahman A, Steinsson K, Franks AG Jr, Sigler L, Hameed S, Fang H, Pham N, Brey R, Weisman MH, McGwin G Jr, Magder LS. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012 Aug;64(8):2677-86. doi: 10.1002/art.34473. **PMID:** 22553077 **Citation:** Gordon C, Jayne D, Pusey C, Adu D, Amoura Z, Aringer M, Ballerin J, Cervera R, Calvo-Alen J, Chizzolini C, Dayer J, Doria A, Ferrario F, Floege J, Guillevin L, Haubitz M, Hiepe F, Houssiau F, Lesavre P, Lightstone L, Meroni P, Meyer O, Moulin B, O'Reilly K, Praga M, Schulze-Koops H, Sinico R, Smith K, Tincani A, Vasconcelos C, Hughes G. European consensus statement on the terminology used in the management of lupus glomerulonephritis. Lupus. 2009 Mar;18(3):257-63. doi: 10.1177/0961203308100481. **PMID:** 19213865 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000003240 - Term: Connective Tissue Diseases - ID: D000001327 - Term: Autoimmune Diseases - ID: D000007154 - Term: Immune System Diseases - ID: D000007674 - Term: Kidney Diseases - ID: D000014570 - Term: Urologic Diseases - ID: D000052776 - Term: Female Urogenital Diseases - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases - ID: D000052801 - Term: Male Urogenital Diseases - ID: D000005921 - Term: Glomerulonephritis ### Condition Browse Module - Browse Branches - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: All - Name: All Conditions - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: BC01 - Name: Infections - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M12338 - Name: Nephritis - Relevance: HIGH - As Found: Nephritis - ID: M11178 - Name: Lupus Nephritis - Relevance: HIGH - As Found: Lupus Nephritis - ID: M11177 - Name: Lupus Erythematosus, Systemic - Relevance: HIGH - As Found: Systemic Lupus Erythematosus - ID: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M21881 - Name: Epstein-Barr Virus Infections - Relevance: LOW - As Found: Unknown - ID: M6464 - Name: Connective Tissue Diseases - Relevance: LOW - As Found: Unknown - ID: M4629 - Name: Autoimmune Diseases - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown - ID: M10698 - Name: Kidney Diseases - Relevance: LOW - As Found: Unknown - ID: M17319 - Name: Urologic Diseases - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M14127 - Name: Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M27095 - Name: Male Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M9031 - Name: Glomerulonephritis - Relevance: LOW - As Found: Unknown - ID: T3523 - Name: Lupus Nephritis - Relevance: HIGH - As Found: Lupus Nephritis - ID: T2525 - Name: Glomerulonephritis - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000009393 - Term: Nephritis - ID: D000008181 - Term: Lupus Nephritis - ID: D000008180 - Term: Lupus Erythematosus, Systemic ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429787 **Brief Title:** Post Marketing Observational Study on Safety of BALFAXAR vs. KCENTRA for Reversal of Vitamin K Antagonist Induced Anticoagulation in Adults Undergoing Urgent Surgery or Invasive Procedure **Official Title:** Post Marketing Observational Study on Safety of BALFAXAR® vs. KCENTRA for Reversal of Vitamin K Antagonist Induced Anticoagulation in Adults Undergoing Urgent Surgery or Invasive Procedure. #### Organization Study ID Info **ID:** LEX-212 #### Organization **Class:** INDUSTRY **Full Name:** Octapharma ### Status Module #### Completion Date **Date:** 2032-06-30 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-21 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2031-12-31 **Type:** ESTIMATED #### Start Date **Date:** 2024-06-30 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Octapharma #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True ### Description Module **Brief Summary:** Post marketing observational study on safety of BALFAXAR vs. KCENTRA for Reversal of Vitamin K Antagonist Induced Anticoagulation in Adults Undergoing Urgent Surgery or Invasive Procedure ### Conditions Module **Conditions:** - Vitamin K-Dependent Coagulation Defect - Significant Bleeding Risk ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 3574 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** BALFAXAR will be administered by intravenous (IV) infusion at a rate of 0.12 mL/kg/min (\~3 units/kg/min), up to a maximum rate of 8.4 mL/min (\~210 units/min). Dosing is individualized based on the patient's baseline International Normalized Ratio (INR) value and body weight **Intervention Names:** - Drug: Balfaxar **Label:** BALFAXAR® (500 IU) #### Arm Group 2 **Description:** KCENTRA will be administered by intravenous infusion at of 0.12 mL/kg/min (\~3 units/kg/min) up to a maximum rate of 8.4 mL/min (\~210 units/min). Dosing is individualized based on the patient's baseline International Normalized Ratio (INR) value and body weight. **Intervention Names:** - Drug: Kcentra **Label:** Kcentra® (500 IU) ### Interventions #### Intervention 1 **Arm Group Labels:** - BALFAXAR® (500 IU) **Description:** BALFAXAR (prothrombin complex concentrate, human-lans) is a blood coagulation factor replacement product indicated for the urgent reversal of acquired coagulation factor deficiency induced by Vitamin K antagonist (VKA, e.g., warfarin) therapy in adult patients with need for an urgent surgery/invasive procedure **Name:** Balfaxar **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Kcentra® (500 IU) **Description:** KCENTRA, Prothrombin Complex Concentrate (Human), is a blood coagulation factor replacement product indicated for the urgent reversal of acquired coagulation factor deficiency induced by Vitamin K antagonist (VKA, e.g., warfarin) therapy in adult patients with: * acute major bleeding or * need for an urgent surgery/invasive procedure **Name:** Kcentra **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Proportion of subjects diagnosed with TEEs within 45 days following VKA reversal treatment with BALFAXAR compared to proportion of subjects diagnosed with TEEs within the same period following VKA reversal treatment with Kcentra. **Measure:** TEEs within 45 days following VKA reversal treatment **Time Frame:** 45 days #### Secondary Outcomes **Description:** Proportion of subjects diagnosed with TEEs within 7 and 14 days following VKA reversal treatment with BALFAXAR compared to proportion of subjects diagnosed with TEEs within the same period following VKA reversal treatment with Kcentra. **Measure:** TEEs within 7 and 14 days following VKA reversal treatment **Time Frame:** 14 days **Description:** Median time to TEE following administration of BALFAXAR compared to median time to TEE following administration of Kcentra **Measure:** Median Time to TEEs **Time Frame:** 45 days **Description:** Proportion of subjects who die from any reason within 7, 14 and 45 days following VKA reversal treatment with BALFAXAR compared to proportion of subjects who die from any reason within the same time period following treatment with Kcentra. **Measure:** All Cause Mortality **Time Frame:** 45 days **Description:** Median time to death following administration of BALFAXAR compared to median time to death following administration of Kcentra **Measure:** Median Time to All Cause Mortality **Time Frame:** 45 days **Description:** Rate of fatal TEEs following treatment with BALFAXAR compared to rate of fatal TEEs following treatment with Kcentra within 7, 14 and 45 days following VKA reversal treatment **Measure:** Rate of Fatal TEEs **Time Frame:** 45 days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Subjects at least 18 years of age. 2. Subjects on VKA treatment. 3. Received 4F-PCC agent, BALFAXAR or Kcentra, for urgent reversal of within 48 hours prior to urgent surgery or invasive procedure. Exclusion Criteria: 1. History of TEE within 90 days before receipt of VKA reversal therapy. 2. Subjects treated with VKA reversal therapy and not undergoing urgent invasive procedure. **Minimum Age:** 18 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Patients at least 18 years of age who are currently on Vitamin K Antagonist treatments and received BALFAXAR or Kcentra for urgent reversal of VKA therapy within 48 hours prior to urgent surgery or invasive procedure. Octapharma will not actively enroll any of the 3,574 projected subjects into the study. Subjects meeting the minimum inclusion and exclusion criteria during the course of routine practice will be added to the study on a monthly basis until the sample size required for the analysis is achieved in each group. ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Patrick Murphy **Phone:** 8663371868 **Role:** CONTACT ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006402 - Term: Hematologic Diseases - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000006474 - Term: Hemorrhagic Disorders ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: BC15 - Name: Blood and Lymph Conditions ### Condition Browse Module - Browse Leaves - ID: M9556 - Name: Hemorrhage - Relevance: LOW - As Found: Unknown - ID: M21977 - Name: Hemostatic Disorders - Relevance: HIGH - As Found: Coagulation Defect - ID: M5059 - Name: Blood Coagulation Disorders - Relevance: HIGH - As Found: Coagulation Defect - ID: M9490 - Name: Hematologic Diseases - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: M9560 - Name: Hemorrhagic Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000020141 - Term: Hemostatic Disorders - ID: D000001778 - Term: Blood Coagulation Disorders ### Intervention Browse Module - Browse Branches - Abbrev: Micro - Name: Micronutrients - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: AnCoag - Name: Anticoagulants - Abbrev: Coag - Name: Coagulants - Abbrev: Vi - Name: Vitamins ### Intervention Browse Module - Browse Leaves - ID: M17558 - Name: Vitamins - Relevance: LOW - As Found: Unknown - ID: M17602 - Name: Warfarin - Relevance: LOW - As Found: Unknown - ID: M16676 - Name: Thrombin - Relevance: LOW - As Found: Unknown - ID: M17555 - Name: Vitamin K - Relevance: LOW - As Found: Unknown - ID: T481 - Name: Vitamin K - Relevance: LOW - As Found: Unknown - ID: T449 - Name: Menadione - Relevance: LOW - As Found: Unknown - ID: T450 - Name: Menaquinone - Relevance: LOW - As Found: Unknown - ID: T452 - Name: Naphthoquinone - Relevance: LOW - As Found: Unknown - ID: T458 - Name: Phylloquinone - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429774 **Brief Title:** Comparative Effectiveness of Intervention in Multi-level Hospitals for Acute Traumatic Brain Injury(Metric-TBI) **Official Title:** Comparative Effectiveness of Intervention in Multi-level Hospitals for Acute Traumatic Brain Injury: a Prospective, Multicenter, Observational Cohort Study #### Organization Study ID Info **ID:** SF 2024-1-2042 #### Organization **Class:** OTHER **Full Name:** Beijing Tiantan Hospital ### Status Module #### Completion Date **Date:** 2026-12-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-23 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2026-12-31 **Type:** ESTIMATED #### Start Date **Date:** 2024-07-01 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-16 **Study First Submit QC Date:** 2024-05-23 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Beijing Tiantan Hospital #### Responsible Party **Investigator Affiliation:** Beijing Tiantan Hospital **Investigator Full Name:** Weiming Liu **Investigator Title:** Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** A prospective, multicenter, observational cohort study is designed to compare the effectiveness of intervention in multi-grade hospitals for acute traumatic brain injury and to optimize clinical outcomes. **Detailed Description:** Traumatic brain injury (TBI) is associated with significant morbidity, mortality, and disability, profoundly impacting public health. This study aims to establish a database for acute craniocerebral trauma within the Beijing-Tianjin-Hebei region, and compiles indicators of hospital treatment capabilities and patient data, including neuroimaging, clinical progression, and rehabilitation prognoses.The study is bifurcated into two segments: the initial phase surveys the current status of acute treatment outcomes for TBI inpatients across hospitals in the Beijing-Tianjin-Hebei region and conducts a comparative effectiveness analysis to identify the clinical interventions to optimize. Subsequent phases build on the former by applying optimized treatment strategies to improve efficacy and establish collaborative optimized treatment protocols. This is a prospective, multicenter, observational study designed to enroll 2,000 patients under the age of 90 years with traumatic brain injury in the presence of clinical symptoms confirmed by computed tomography or magnetic resonance imaging.The primary outcome is the Extended Glasgow Outcome Score within 12 months. Secondary outcomes include the Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9(PHQ-9), Rivermead post-concussion symptoms questionnaire(RPQ), PTSD Checklist-5 Version(PCL-5)，Six-Item Screener (SIS) and 12-Item Short-Form Health Survey version 2(SF-12v2). The objective of this study is anticipated to the Beijing-Tianjin-Hebei region a 20 percent increase in the number of cases treated by optimized clinical practice guidelines and a 10 percent decrement in mortality and disability rates among TBI patients in the region. ### Conditions Module **Conditions:** - Traumatic Brain Injury **Keywords:** - Traumatic Brain Injury - Beijing-Tianjin-Hebei region - Database - Comparative effectiveness of intervention - Clinical Treatment Guideline ### Design Module #### Bio Spec **Description:** * vein blood * hematoma fluid * dura mater * hematoma outer membrane **Retention:** SAMPLES_WITH_DNA #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 2000 **Type:** ESTIMATED **Patient Registry:** True **Study Type:** OBSERVATIONAL **Target Duration:** 1 Year ### Arms Interventions Module #### Arm Group 1 **Description:** TBI patients recruited from neurosurgical departments at 50 medical centers in China have apparent clinical symptoms that are confirmed by computed tomography or magnetic resonance imaging. The exclusion criteria are those who fulfill one of the following conditions: 1. patients ≥90 years of age; 2. patients who did not accept follow-up visits or were unable to complete follow-up assessments; 3. patients with incomplete information; 4. patients who did not obtain written informed consent; 5. patients with concomitant cancer or other serious illnesses. **Intervention Names:** - Other: Neurological function - Other: Mental State, cognitive function, and life quality assessment - Other: Peripheral blood test - Other: Hematoma test **Label:** TBI Group ### Interventions #### Intervention 1 **Arm Group Labels:** - TBI Group **Description:** Neurological function will be examined using Glasgow Coma Scale (GCS) and Extended Glasgow Outcome Scale (GOSE).The GOSE was created as an advancement from the original GOS. The GOSE score categorizes the prognosis of patients with traumatic brain injury into eight categories.The 8 categories are: Dead, Vegetative State, Lower Severe Disability, Upper Severe Disability, Lower Moderate Disability, Upper Moderate Disability, Lower Good Recovery, and Upper Good Recovery. **Name:** Neurological function **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - TBI Group **Description:** Mental State, cognitive function, and life quality will be examined using the Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9(PHQ-9), Rivermead post-concussion symptoms questionnaire(RPQ), PTSD Checklist-5 Version(PCL-5)，Six-Item Screener（SIS） and 12-Item Short-Form Health Survey version 2(SF-12v2). **Name:** Mental State, cognitive function, and life quality assessment **Type:** OTHER #### Intervention 3 **Arm Group Labels:** - TBI Group **Description:** Collect peripheral blood samples from patients. **Name:** Peripheral blood test **Type:** OTHER #### Intervention 4 **Arm Group Labels:** - TBI Group **Description:** Collect hematoma fluid, dura mater, and hematoma outer membrane samples from patients. **Name:** Hematoma test **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** The Extended Glasgow Outcome Scores(GOSE) range from 1 to 8, with higher scores indicating a better outcome. The summary of the scale is below:1.Dead;2. Vegetative State;3. Lower Severe Disability;4. Upper Severe Disability;5. Lower Moderate Disability;6. Upper Moderate Disability;7. Lower Good Recovery;8.Upper Good Recovery.Therefore, a score of 1 represents the worst outcome (death), and a score of 8 represents the best outcome (upper good recovery). The rates of death or severe disability (GOSE scores 1-3) due to traumatic brain injury in the short term (at discharge) and in the long term (3, 6, and 12 months post-discharge) give an indication of the extent to which a patient recovers from different treatments. **Measure:** Difference in the Extended Glasgow Outcome Score **Time Frame:** From discharge up to 12 months postoperatively #### Secondary Outcomes **Description:** Patients were scored on their subsequent level of mental health at 3, 6, and 12 months after discharge based on the Generalized Anxiety Disorder-7 Scale(GAD-7). The GAD-7 scale consists of seven items, each describing a symptom of Generalized Anxiety Disorder(GAD), and respondents rate how often they've been bothered by each symptom over the past two weeks.The GAD-7 score of 10 suggests moderate anxiety, on a scale ranging from 0 (minimal anxiety) to 21 (severe anxiety), with higher scores indicating worse outcomes. **Measure:** Difference in the Generalized Anxiety Disorder-7 Scale in post-traumatic mental health recovery **Time Frame:** From discharge up to 12 months postoperatively **Description:** Patients were scored on their subsequent level of mental health at 3, 6, and 12 months after discharge based on the Patient Health Questionnaire-9 Scale(PHQ-9). The PHQ-9 scale consists of nine items, each describing a symptom of depression, and respondents rate how often they've been bothered by each symptom over the past two weeks. The PHQ-9 scores between 10-14 suggest moderate depression, on a scale ranging from 0 (minimal depression) to 27 (severe depression), with higher scores indicating worse outcomes. **Measure:** Difference in the Patient Health Questionnaire-9 Scale in post-traumatic mental health recovery **Time Frame:** From discharge up to 12 months postoperatively **Description:** Patients were scored on their subsequent level of mental health at 3, 6, and 12 months after discharge based on the Rivermead Post-Concussive Symptoms Questionnaire(RPQ). The RPQ score ranges from 0 (no symptoms) to 64 (severe symptoms). Higher scores on the RPQ indicate a greater severity of post-concussive symptoms and a worse outcome. This information helps healthcare providers assess the impact of the concussion on the patient's daily life and track their recovery progress. **Measure:** Difference in the Rivermead Post-Concussive Symptoms Questionnaire Scale in post-traumatic mental health recovery **Time Frame:** From discharge up to 12 months postoperatively **Description:** Patients were scored on their subsequent level of mental health at 3, 6, and 12 months after discharge based on the Post-Traumatic Stress Disorder Checklist-5 (PCL-5). Each of the 20 items on the PCL-5 is rated on a scale from 0 ("Not at all") to 4 ("Extremely"). The PCL-5 score ranges from 0 to 80, with higher scores indicating worse Post-traumatic stress disorder(PTSD) symptoms. **Measure:** Difference in the Post-Traumatic Stress Disorder Checklist-5 Scale in post-traumatic mental health recovery **Time Frame:** From discharge up to 12 months postoperatively **Description:** Patients were scored on their subsequent level of quality of life at 3, 6, and 12 months after discharge based on different scores on the 12-item Short-Form Health Survey 2 (SF-12v2). The SF-12v2 provides two summary scores: the Physical Component Summary (PCS) score and the Mental Component Summary (MCS) score. For both the PCS and MCS scores range from 0(the lowest level of health) to 100(the highest level of health). Higher scores on the PCS and MCS indicate better physical and mental health, respectively. **Measure:** Difference in life quality assessment **Time Frame:** From discharge up to 12 months postoperatively **Description:** Patients were scored on their subsequent level of cognitive function at 3, 6, and 12 months after discharge based on different scores on the Six-Item Screener (SIS). The SIS is a brief cognitive assessment tool used primarily to screen for cognitive impairment. The SIS assesses orientation and recall, two critical components often affected in cognitive disorders such as dementia.It ranges from 0 to 6, with higher scores mean a better outcome in terms of cognitive function. **Measure:** Difference in cognitive function **Time Frame:** From discharge up to 12 months postoperatively **Description:** Rates of complications and adverse events during hospitalization and 12 months after discharge. **Measure:** Rate of complications and adverse events **Time Frame:** From discharge up to 12 months postoperatively ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patient (1 years to 89 years) presenting with clinical symptoms of traumatic brain injury * Traumatic brain injury verified on cranial computed tomography or magnetic resonance imaging * Written informed consent from patients or their next of kin according to the patient's cognitive status Exclusion Criteria: * patients ≥90 years of age * patients who did not accept follow-up visits or were unable to complete follow-up assessments * patients with incomplete information * patients who did not obtain written informed consent * patients with concomitant cancer or other serious illnesses **Maximum Age:** 89 Years **Minimum Age:** 1 Year **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT **Study Population:** TBI patients recruited from neurosurgical departments at 50 medical centers in China have apparent clinical symptoms that are confirmed by computed tomography or magnetic resonance imaging. ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Weiming Liu, M.D. **Phone:** 13701182770 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Yu Shi, M.D. **Phone:** 13611533819 **Role:** CONTACT #### Locations **Location 1:** **City:** Beijing **Country:** China **Facility:** Beijing Fengtai You'anmen Hospital **State:** Beijing **Zip:** 100000 **Location 2:** **City:** Beijing **Country:** China **Facility:** Beijing Huairou Hospital **State:** Beijing **Zip:** 100000 **Location 3:** **City:** Beijing **Country:** China **Facility:** Beijing HuaSheng Rehabilitation Hospital **State:** Beijing **Zip:** 100000 **Location 4:** **City:** Beijing **Country:** China **Facility:** Beijing Luhe Hospital,Capital Medical University **State:** Beijing **Zip:** 100000 **Location 5:** **City:** Beijing **Country:** China **Facility:** Beijing Tsinghua Changgung Hospital **State:** Beijing **Zip:** 100000 **Location 6:** **City:** Beijing **Country:** China **Facility:** Peking University People's Hospital **State:** Beijing **Zip:** 100000 **Location 7:** **City:** Beijing **Country:** China **Facility:** Beijing Chaoyang Hospital, Capital Medical University **State:** Beijing **Zip:** 100020 **Location 8:** **City:** Beijing **Country:** China **Facility:** Beijing Chaoyang Integrative Medicine Rescue And First Aid Hospital **State:** Beijing **Zip:** 100020 **Location 9:** **City:** Beijing **Country:** China **Facility:** Beijing Daxing District People's Hospital **State:** Beijing **Zip:** 100020 **Location 10:** **City:** Beijing **Country:** China **Facility:** Peking University International Hospital **State:** Beijing **Zip:** 100020 **Location 11:** **City:** Beijing **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Weiming Liu, MD - **Phone:** 13701182770 - **Phone Ext:** +86 - **Role:** CONTACT ***Contact 2:*** - **Name:** Weiming Liu, MD - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 3:*** - **Name:** Guoyi Gao, MD - **Role:** SUB_INVESTIGATOR ***Contact 4:*** - **Name:** Dongling Sun, MD - **Role:** SUB_INVESTIGATOR **Country:** China **Facility:** Beijing Tiantan Hospital, Capital Medical University **State:** Beijing **Zip:** 100070 **Location 12:** **City:** Beijing **Country:** China **Facility:** Beijing Pinggu Hospital **State:** Beijing **Zip:** 101200 **Location 13:** **City:** Beijing **Country:** China **Facility:** Beijing Changping Hospital **State:** Beijing **Zip:** 102200 **Location 14:** **City:** Beijing **Country:** China **Facility:** Beijing Mentougou District Hospital **State:** Beijing **Zip:** 102300 **Location 15:** **City:** Beijing **Country:** China **Facility:** Liangxiang Hospital **State:** Beijing **Zip:** 102400 **Location 16:** **City:** Beijing **Country:** China **Facility:** The First Hospital of Fangshan District, Bejing **State:** Beijing **Zip:** 102400 **Location 17:** **City:** Baoding **Country:** China **Facility:** Affiliated Hospital Of Hebei University **State:** Hebei **Zip:** 071000 **Location 18:** **City:** Baoding **Country:** China **Facility:** Bao Ding No.1 Central Hospital **State:** Hebei **Zip:** 071000 **Location 19:** **City:** Baoding **Country:** China **Facility:** The No.2 Hospital of Baoding **State:** Hebei **Zip:** 071000 **Location 20:** **City:** Baoding **Country:** China **Facility:** Anguo Hospital **State:** Hebei **Zip:** 071200 **Location 21:** **City:** Baoding **Country:** China **Facility:** Xiongxian Hospital **State:** Hebei **Zip:** 071800 **Location 22:** **City:** Baoding **Country:** China **Facility:** The Fourth Central Hospital of Baoding City **State:** Hebei **Zip:** 072350 **Location 23:** **City:** Baoding **Country:** China **Facility:** Gaobeidian Hospital **State:** Hebei **Zip:** 074099 **Location 24:** **City:** Cangzhou **Country:** China **Facility:** Suning Hospital **State:** Hebei **Zip:** 062350 **Location 25:** **City:** Chengde **Country:** China **Facility:** Affiliated Hospital Of Chengde Medical University **State:** Hebei **Zip:** 067000 **Location 26:** **City:** Chengde **Country:** China **Facility:** Luanping Hospital **State:** Hebei **Zip:** 068250 **Location 27:** **City:** Handan **Country:** China **Facility:** Handan Central Hospital **State:** Hebei **Zip:** 056000 **Location 28:** **City:** Handan **Country:** China **Facility:** Hangang Hospital **State:** Hebei **Zip:** 056000 **Location 29:** **City:** Handan **Country:** China **Facility:** Weixian Chinese Traditional Medicine Hospital **State:** Hebei **Zip:** 056800 **Location 30:** **City:** Handan **Country:** China **Facility:** The No.1 Hospital Of Yongnian District Handan City **State:** Hebei **Zip:** 057150 **Location 31:** **City:** Hengyang **Country:** China **Facility:** Raoyang People's Hospital **State:** Hebei **Zip:** 053900 **Location 32:** **City:** Langfang **Country:** China **Facility:** Langfang People's Hospital **State:** Hebei **Zip:** 065000 **Location 33:** **City:** Langfang **Country:** China **Facility:** Yanjiao Fuhe No.1 Hospital **State:** Hebei **Zip:** 065201 **Location 34:** **City:** Langfang **Country:** China **Facility:** Dachang Hui Autonomous County People's Hospital **State:** Hebei **Zip:** 065300 **Location 35:** **City:** Langfang **Country:** China **Facility:** Xianghe Hospital **State:** Hebei **Zip:** 065400 **Location 36:** **City:** Shijiazhuang **Country:** China **Facility:** Hebei Medical University Third Hospital **State:** Hebei **Zip:** 050000 **Location 37:** **City:** Shijiazhuang **Country:** China **Facility:** The Fourth Hospital of Hebei Medical University **State:** Hebei **Zip:** 050000 **Location 38:** **City:** Shijiazhuang **Country:** China **Facility:** The Third Hospital Of Shijiazhuang **State:** Hebei **Zip:** 050000 **Location 39:** **City:** Shijiazhuang **Country:** China **Facility:** Hebei Chest Hospital **State:** Hebei **Zip:** 050041 **Location 40:** **City:** Shijiazhuang **Country:** China **Facility:** Jingxing Hospital **State:** Hebei **Zip:** 050300 **Location 41:** **City:** Shijiazhuang **Country:** China **Facility:** Xibaipo Rescue Center **State:** Hebei **Zip:** 050411 **Location 42:** **City:** Shijiazhuang **Country:** China **Facility:** Xinle Chinese Traditional Medicine Hospital **State:** Hebei **Zip:** 050700 **Location 43:** **City:** Shijiazhuang **Country:** China **Facility:** Yuanshi Chinese Traditional Medicine Hospital **State:** Hebei **Zip:** 051130 **Location 44:** **City:** Shijiazhuang **Country:** China **Facility:** Gaoyi Hospital **State:** Hebei **Zip:** 051330 **Location 45:** **City:** Tangshan **Country:** China **Facility:** Tangshan Fengrun People's Hospital **State:** Hebei **Zip:** 063000 **Location 46:** **City:** Tangshan **Country:** China **Facility:** Tangshan Workers' Hospital **State:** Hebei **Zip:** 063000 **Location 47:** **City:** Tangshan **Country:** China **Facility:** People's Hospital Of Zunhua **State:** Hebei **Zip:** 064200 **Location 48:** **City:** Xingtai **Country:** China **Facility:** Xingtai Central Hospital **State:** Hebei **Zip:** 054000 **Location 49:** **City:** Xingtai **Country:** China **Facility:** LinCheng People's Hospital **State:** Hebei **Zip:** 054300 **Location 50:** **City:** Xingtai **Country:** China **Facility:** Qinghe Central Hospital **State:** Hebei **Zip:** 054800 **Location 51:** **City:** Tianjin **Country:** China **Facility:** Tianjin Hospital **State:** Tianjin **Zip:** 300000 #### Overall Officials **Official 1:** **Affiliation:** Beijing Tiantan Hospital **Name:** Weiming Liu, M.D. **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Capizzi A, Woo J, Verduzco-Gutierrez M. Traumatic Brain Injury: An Overview of Epidemiology, Pathophysiology, and Medical Management. Med Clin North Am. 2020 Mar;104(2):213-238. doi: 10.1016/j.mcna.2019.11.001. **PMID:** 32035565 **Citation:** Galgano M, Toshkezi G, Qiu X, Russell T, Chin L, Zhao LR. Traumatic Brain Injury: Current Treatment Strategies and Future Endeavors. Cell Transplant. 2017 Jul;26(7):1118-1130. doi: 10.1177/0963689717714102. **PMID:** 28933211 **Citation:** Jiang JY, Gao GY, Feng JF, Mao Q, Chen LG, Yang XF, Liu JF, Wang YH, Qiu BH, Huang XJ. Traumatic brain injury in China. Lancet Neurol. 2019 Mar;18(3):286-295. doi: 10.1016/S1474-4422(18)30469-1. Epub 2019 Feb 12. **PMID:** 30784557 **Citation:** Stocchetti N, Carbonara M, Citerio G, Ercole A, Skrifvars MB, Smielewski P, Zoerle T, Menon DK. Severe traumatic brain injury: targeted management in the intensive care unit. Lancet Neurol. 2017 Jun;16(6):452-464. doi: 10.1016/S1474-4422(17)30118-7. **PMID:** 28504109 **Citation:** Steyerberg EW, Wiegers E, Sewalt C, Buki A, Citerio G, De Keyser V, Ercole A, Kunzmann K, Lanyon L, Lecky F, Lingsma H, Manley G, Nelson D, Peul W, Stocchetti N, von Steinbuchel N, Vande Vyvere T, Verheyden J, Wilson L, Maas AIR, Menon DK; CENTER-TBI Participants and Investigators. Case-mix, care pathways, and outcomes in patients with traumatic brain injury in CENTER-TBI: a European prospective, multicentre, longitudinal, cohort study. Lancet Neurol. 2019 Oct;18(10):923-934. doi: 10.1016/S1474-4422(19)30232-7. **PMID:** 31526754 **Citation:** Silverberg ND, Duhaime AC, Iaccarino MA. Mild Traumatic Brain Injury in 2019-2020. JAMA. 2020 Jan 14;323(2):177-178. doi: 10.1001/jama.2019.18134. No abstract available. **PMID:** 31816030 **Citation:** Sun D, Jiang B, Ru X, Sun H, Fu J, Wu S, Wang L, Wang L, Zhang M, Liu B, Wang W; for the NESS-China investigators. Prevalence and Altered Causes of Traumatic Brain Injury in China: A Nationwide Survey in 2013. Neuroepidemiology. 2020;54(2):106-113. doi: 10.1159/000501911. Epub 2019 Dec 18. **PMID:** 31851999 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000006259 - Term: Craniocerebral Trauma - ID: D000020196 - Term: Trauma, Nervous System ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M5207 - Name: Brain Injuries - Relevance: HIGH - As Found: Brain Injury - ID: M628 - Name: Brain Injuries, Traumatic - Relevance: HIGH - As Found: Traumatic Brain Injury - ID: M17685 - Name: Wounds and Injuries - Relevance: HIGH - As Found: Injury - ID: M5204 - Name: Brain Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M9349 - Name: Craniocerebral Trauma - Relevance: LOW - As Found: Unknown - ID: M22023 - Name: Trauma, Nervous System - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001930 - Term: Brain Injuries - ID: D000070642 - Term: Brain Injuries, Traumatic - ID: D000014947 - Term: Wounds and Injuries ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M11767 - Name: Metronidazole - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429761 **Acronym:** STRIDE **Brief Title:** A PROSPECTIVE, MULTI-CENTER, PHASE 4 STUDY TO ASSESS THE SAFETY OF TRASTUZUMAB DERUXTECAN, AN ANTI-HER2-ANTIBODY DRUG CONJUGATE IN INDIAN PATIENTS WITH UNRESECTABLE OR METASTATIC HER2-POSITIVE BREAST CANCER WHO HAVE RECEIVED A PRIOR ANTI-HER2-BASED REGIMEN **Official Title:** A PROSPECTIVE, MULTI-CENTER, PHASE 4, SINGLE ARM STUDY TO ASSESS THE SAFETY OF TRASTUZUMAB DERUXTECAN, AN ANTI-HER2-ANTIBODY DRUG CONJUGATE IN INDIAN PATIENTS WITH UNRESECTABLE OR METASTATIC HER2-POSITIVE BREAST CANCER WHO HAVE RECEIVED A PRIOR ANTI-HER2-BASED REGIMEN #### Organization Study ID Info **ID:** D9673L00012 #### Organization **Class:** INDUSTRY **Full Name:** AstraZeneca ### Status Module #### Completion Date **Date:** 2026-04-30 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-21 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2026-04-30 **Type:** ESTIMATED #### Start Date **Date:** 2024-09-30 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** AstraZeneca #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** A PROSPECTIVE, MULTI-CENTER, PHASE 4, SINGLE ARM STUDY TO ASSESS THE SAFETY OF TRASTUZUMAB DERUXTECAN, AN ANTI-HER2-ANTIBODY DRUG CONJUGATE IN INDIAN PATIENTS WITH UNRESECTABLE OR METASTATIC HER2-POSITIVE BREAST CANCER WHO HAVE RECEIVED A PRIOR ANTI-HER2-BASED REGIMEN **Detailed Description:** As per recommendation from DCGI, the current phase-IV study is planned with an aim to assess the safety of Trastuzumab deruxtecan in Indian subjects receiving the drug as per the approved label indications in India in accordance with the requirements of the Health Authorities of India. The data obtained from the present study will help to understand the safety profile of Trastuzumab deruxtecan among Indian patients. ### Conditions Module **Conditions:** - BREAST CANCER ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 100 **Type:** ESTIMATED **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Trastuzumab deruxtecan **Intervention Names:** - Drug: Trastuzumab deruxtecan **Label:** Single Arm **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Single Arm **Description:** IV infusion **Name:** Trastuzumab deruxtecan **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Rate of adverse events **Measure:** To assess the safety of trastuzumab deruxtecan in adult Indian patients **Time Frame:** 6 Months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1 Participant must be \>18 years of age inclusive, at the time of signing the informed consent. 2 Patients who are willing and capable of giving signed informed consent as described in Appendix A, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. 3 Participants with pathologically documented breast cancer that: * is unresectable or metastatic * HER2-positive expression (IHC 3+ or IHC 2+ with ISH positive) as confirmed by laboratory assessment within last 1 year of study enrolment. * was previously treated with an anti HER-2 based regimen 4 Adequate bone marrow function, within 14 d before enrolment, defined as: a. Absolute neutrophil count ≥ 1.5 × 109/L (granulocyte colony-stimulating factor administration is not allowed within 1 wk prior to Screening assessment); b. Platelet count ≥ 100 × 109/L (Platelet transfusion is not allowed within 1 wk prior to Screening assessment); c. Hemoglobin level ≥ 9.0 g/dL (Red blood cell transfusion is not allowed within 1 wk prior to Screening assessment). 5 Adequate renal function within 14 d before enrolment, defined as: * Creatinine clearance ≥ 30 mL/min, as calculated using the Cockcroft-Gault equation (CLcr (mL/min) = \[140 - age (years)\] × weight (kg) {× 0.85 for females}; 72 × serum creatinine (mg/dL) 6 Adequate hepatic function within 14 d before enrolment, defined as: * Total bilirubin ≤ 1.5 × upper limit of normal (ULN) if no liver metastases or \< 3 × ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline, and * Aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 3 × ULN 7 Adequate blood clotting function within 14 d before enrolment, defined as: * International normalized ratio/prothrombin time ≤ 1.5 × ULN and either partial thromboplastin or activated partial thromboplastin time ≤ 1.5 × ULN 8 Female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least 7 mo after the last dose of trastuzumab deruxtecan. Male subjects must agree to inform all potential female partners that they are participating in a clinical trial of a drug that may cause birth defects. Male subjects must also agree to either avoid intercourse or that they and/or any female partners of reproductive/childbearing potential will use a highly effective form of contraception during and upon completion of the study and for at least 4.5 mo after the last dose of trastuzumab deruxtecan. Methods considered as highly effective methods of contraception include: * Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: o Oral o Intravaginal o Transdermal * Progestogen-only hormonal contraception associated with inhibition of ovulation: o Oral o Injectable o Implantable * Intrauterine device * Intrauterine hormone-releasing system * Bilateral tubal occlusion * Vasectomized partner * Complete sexual abstinence defined as refraining from heterosexual intercourse during and upon completion of the study and for at least 7 mo for female subjects (4.5 mo for male subjects) after the last dose of trastuzumab deruxtecan. True abstinence must be in line with the preferred and usual lifestyle of the subject. Periodic abstinence (calendar, symptothermal, postovulation methods) is not an acceptable method of contraception. Non-childbearing potential is defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 mo of spontaneous amenorrhea (in questionable cases, a blood sample with simultaneous follicle-stimulating hormone \> 40 mIU/mL and estradiol \< 40 pg/mL \[\< 147 pmol/L\] is confirmatory). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use 1 of the contraception methods outlined for women of childbearing potential if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status prior to study enrollment. For most forms of HRT, at least 2 to 4 wk will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their postmenopausal status, they can resume use of HRT during the study without use of a contraceptive method. 9 Male subjects must not freeze or donate sperm throughout the study period beginning at Cycle 1 Day 1 and for at least 4.5 mo after the last dose of trastuzumab deruxtecan or Preservation of sperm should be considered prior to enrollment in this study. 10 Female subjects must not donate ova or retrieve them for their own use from the time of Screening and throughout the study treatment period, and for at least 7 mo after the last dose of trastuzumab deruxtecan Exclusion Criteria: 1. Prior treatment with T-DXd 2. Uncontrolled or significant cardiovascular disease, including any of the following: 1. History of myocardial infarction within 6 months before enrolment 2. History of symptomatic congestive heart failure (New York Heart Association Class II to IV); 3. Corrected QT interval (QTc) prolongation to \> 470 ms (females) or \>450 ms (male); 4. LVEF \< 50% within 28 d prior to treatment initiation. 3. Has a history of (noninfectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening. 4. Spinal cord compression or clinically active central nervous system (CNS) metastases, defined as untreated or symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. * Subjects with clinically inactive brain metastases may be included in the study. * Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 wk must have elapsed between the end of whole brain radiotherapy and study enrollment. 5. Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product or to other mAbs. 6. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals. 7. Known human immunodeficiency virus (HIV) infection or active hepatitis B or C infection. 8. Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤ 1 or baseline. Subjects with chronic Grade 2 toxicities may be eligible per the discretion of the investigator after consultation with the Sponsor Medical Monitor or designee (eg, Grade 2 chemotherapy-induced neuropathy). 9. Therapeutic radiation therapy or major surgery within 4 wk before enrolment or palliative stereotactic radiation therapy within 2 wk before enrolment. 10. Systemic treatment with anticancer therapy (immunotherapy \[non-antibody-based therapy\], retinoid therapy, or hormonal therapy) within 3 wk before enrolment; antibody-based-anticancer-therapy within 4 wk before enrolment; or treatment with nitrosoureas or mitomycin C within 6 wk before randomization; or treatment with small-molecule targeted agents within 2 wk or 5 half-lives before enrolment, whichever is longer. 11. Participation in a therapeutic clinical study within 3 wk before enrolment (for small-molecule targeted agents, this non-participation period is 2 wk or 5 half-lives, whichever is longer), or current participation in other investigational procedures. 12. Pregnant, breastfeeding, or planning to become pregnant. 13. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease \[COPD\], restrictive lung disease, pleural effusion etc), and any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (ie, rheumatoid arthritis, Sjögren's, sarcoidosis etc), or prior pneumonectomy **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** AstraZeneca Clinical Study Information Center **Phone:** 1-877-240-9479 **Role:** CONTACT ### IPD Sharing Statement Module **Access Criteria:** When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. **Description:** Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved. **Info Types:** - STUDY_PROTOCOL - SAP **IPD Sharing:** YES **Time Frame:** AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. **URL:** https://vivli.org/ ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000001941 - Term: Breast Diseases - ID: D000012871 - Term: Skin Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M5220 - Name: Breast Neoplasms - Relevance: HIGH - As Found: Breast Cancer - ID: M5218 - Name: Breast Diseases - Relevance: LOW - As Found: Unknown - ID: M15674 - Name: Skin Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001943 - Term: Breast Neoplasms ### Intervention Browse Module - Ancestors - ID: D000074322 - Term: Antineoplastic Agents, Immunological - ID: D000000970 - Term: Antineoplastic Agents - ID: D000018796 - Term: Immunoconjugates - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M325 - Name: Trastuzumab - Relevance: HIGH - As Found: Quality - ID: M4225 - Name: Antibodies - Relevance: LOW - As Found: Unknown - ID: M10184 - Name: Immunoglobulins - Relevance: LOW - As Found: Unknown - ID: M233243 - Name: Trastuzumab deruxtecan - Relevance: HIGH - As Found: Peginterferon Alfa-2a - ID: M1346 - Name: Antineoplastic Agents, Immunological - Relevance: LOW - As Found: Unknown - ID: M20855 - Name: Immunoconjugates - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000068878 - Term: Trastuzumab - ID: C000614160 - Term: Trastuzumab deruxtecan ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429748 **Acronym:** SET **Brief Title:** Symptom Evaluation Following Repetitive Transcranial Magnetic Stimulation **Official Title:** A Prospective Study to Evaluate Symptoms Following Repetitive Transcranial Magnetic Stimulation (rTMS) #### Organization Study ID Info **ID:** 44-50019-000 #### Organization **Class:** OTHER **Full Name:** Neuronetics ### Status Module #### Completion Date **Date:** 2025-12 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-21 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2025-03 **Type:** ESTIMATED #### Start Date **Date:** 2024-05-15 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Neuronetics #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** True **Is FDA Regulated Drug:** False **Is US Export:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** A prospective study to evaluate symptoms following repetitive transcranial Magnetic stimulation. **Detailed Description:** Open-label, multicenter, prospective pilot study conducted in an adult population receiving rTMS treatment. ### Conditions Module **Conditions:** - Neurologic Symptoms ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 30 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Single Group **Intervention Names:** - Device: rTMS **Label:** Open Label **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Open Label **Description:** repetitive Transcranial Magnetic Stimultion **Name:** rTMS **Type:** DEVICE ### Outcomes Module #### Other Outcomes **Description:** Treatment related Adverse Events **Measure:** Safety Outcome **Time Frame:** 16 weeks #### Primary Outcomes **Description:** Assess changes in multiple symptoms scores based on patient reported questionnaires from baseline to end of acute. **Measure:** Changes in multiple symptoms after rTMS treatment. **Time Frame:** 4 weeks #### Secondary Outcomes **Description:** Assess changes in multiple symptoms scores based on patient reported questionnaires from baseline to final follow-up visit. **Measure:** Durability of changes in symptoms **Time Frame:** 16 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Adults, 22 to 70 years of age 2. Voluntarily provides written informed consent and agree to comply with study procedures, including attending all study visits and completing all study assessments. 3. Score \> or = 8 on ISI scale 4. If subject is on any psychiatric or sleep medication, dose must be stable for two weeks prior to enrollment and remain stable throughout the trial. 5. If female, not breastfeeding, no known or suspected pregnancy, a status of nonchildbearing potential or use of an acceptable form of birth control. 6. Subject on stable dose regime for other concurrent medications like hormonal therapy for menopause transition etc. Exclusion Criteria: 1. Subject meets any one or more of the contraindications for TMS Therapy per current treatment guidelines as determined by the PI. 2. History of head trauma associated with loss of consciousness or diagnosed as concussion. 3. History of fainting, syncope, hearing problems or ringing in the ears (tinnitus) 4. Has any metallic implant(s) in or near the head (e.g., pacemaker, defibrillator, neurostimulator, etc.) including any splinters, fragments, clips, etc. 5. Has an implanted stimulator device (including device leads) in or near the head. (e.g. deep brain stimulator, cochlear implant, vagus nerve stimulator.) 6. Has medication infusion device. 7. Subjects with any prior TMS or MRI complications, or any other issues/circumstance which, in the opinion of the investigator, might interfere with safety, study participation, or which might confound data interpretation. 8. PHQ-9 total score \> or = 10 or QIDS total score \> or = 11. 9. Drug abuse or dependence of the illicit substance. (Abuse or Dependence, as defined by DSM-V-TR) 10. Current diagnosis or known history of neurologic disease (e.g., epilepsy, convulsion, seizure) 11. Other known disorder (e.g., narcolepsy, a breathing-related sleep disorder like Obstructive Sleep Apnea, a circadian rhythm sleep-wake disorder, a parasomnia) as defined by DSM-V-TR. 12. Has a clinically significant abnormality on the screening examination. 13. Participation in any clinical trial with an investigational drug or device within the past month or concurrent with study participation. **Maximum Age:** 70 Years **Minimum Age:** 22 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Neha Goyal **Phone:** 7635281599 **Role:** CONTACT #### Locations **Location 1:** **City:** Charlotte **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Robyn Allen, RN - **Phone:** 704-333-9113 - **Role:** CONTACT ***Contact 2:*** - **Name:** Elizabeth Rostan, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** Charlotte Skin and Laser **State:** North Carolina **Status:** RECRUITING **Zip:** 28207 #### Overall Officials **Official 1:** **Affiliation:** Neuronetics **Name:** Steve Erickson **Role:** STUDY_DIRECTOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009422 - Term: Nervous System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M12404 - Name: Neurologic Manifestations - Relevance: HIGH - As Found: Neurologic Symptoms ### Condition Browse Module - Meshes - ID: D000009461 - Term: Neurologic Manifestations ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429735 **Acronym:** PRIME **Brief Title:** Precise Robotically Implanted Brain-Computer Interface **Official Title:** PRIME: An Early Feasibility Study of a Robotically Implanted Brain-Computer Interface for the Control of External Devices #### Organization Study ID Info **ID:** N1-EFS-001 #### Organization **Class:** INDUSTRY **Full Name:** Neuralink Corp ### Status Module #### Completion Date **Date:** 2031-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-30 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-28 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2026-01 **Type:** ESTIMATED #### Start Date **Date:** 2024-01-09 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Neuralink Corp #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** True **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** The PRIME Study is a first-in-human early feasibility study to evaluate the initial clinical safety and device functionality of the Neuralink N1 Implant and R1 Robot device designs in participants with tetraparesis or tetraplegia. The N1 Implant is a skull-mounted, wireless, rechargeable implant connected to electrode threads that are implanted in the brain by the R1 Robot, a robotic electrode thread inserter. ### Conditions Module **Conditions:** - Tetraplegia/Tetraparesis - Quadriplegia - Cervical Spinal Cord Injury - Amyotrophic Lateral Sclerosis - Quadriplegia/Tetraplegia - Tetraplegic; Paralysis **Keywords:** - spinal cord injury, ALS, brain computer interface, BCI ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** DEVICE_FEASIBILITY #### Enrollment Info **Count:** 3 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Implantation of the N1 Implant by the R1 Robot. **Intervention Names:** - Device: N1 Implant - Device: R1 Robot **Label:** Neuralink N1 Implant and R1 Robot **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Neuralink N1 Implant and R1 Robot **Description:** The N1 Implant is a type of implantable brain-computer interface **Name:** N1 Implant **Other Names:** - Neuralink N1 Implant, N1, Telepathy, Link **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - Neuralink N1 Implant and R1 Robot **Description:** The R1 Robot is a robotic electrode thread inserter that implants the N1 Implant. **Name:** R1 Robot **Other Names:** - R1, Neuralink R1 Robot **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Measure:** Device-Related Adverse Events (AE) **Time Frame:** 12 months post-implant **Measure:** Procedure-Related Adverse Events (AE) **Time Frame:** 12 months post-implant #### Secondary Outcomes **Measure:** Device-Related Adverse Events (AE) **Time Frame:** Up to 72 months post-implant **Measure:** Procedure-Related Adverse Events (AE) **Time Frame:** Up to 72 months post-implant ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Severe quadriplegia (tetraplegia) due to spinal cord injury or amyotrophic lateral sclerosis (ALS) for at least 1 year without improvement, where quadriplegia is defined as having very limited or no hand, wrist, and arm movement and all levels below * Life expectancy ≥ 12 months. * Ability to communicate in English * Presence of a stable caregiver Exclusion Criteria * Moderate to high risk for serious perioperative adverse events * Active implanted devices * Morbid obesity (Body Mass Index \> 40) * History of poorly controlled seizures or epilepsy * History of poorly controlled diabetes * Requires magnetic resonance imaging (MRI) for any ongoing medical conditions * Acquired or hereditary immunosuppression * Use of smoking tobacco or other tobacco products * Psychiatric or psychological disorder * Brain MRI demonstrating hemorrhage, tumor, distorted or adverse anatomy. * Any condition which, in the opinion of the Investigator, would compromise your ability to safely participate in the study or undergo the implantation procedure **Maximum Age:** 75 Years **Minimum Age:** 22 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Head of Clinical **Phone:** 818-527-2710 **Role:** CONTACT #### Locations **Location 1:** **City:** Phoenix **Contacts:** ***Contact 1:*** - **Name:** Francisco Ponce, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** Barrow Neurological Institute **State:** Arizona **Status:** RECRUITING **Zip:** 85013 #### Overall Officials **Official 1:** **Affiliation:** Barrow Neurological Institute **Name:** Francisco Ponce, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### See Also Links **Label:** https://neuralink.com/ **URL:** https://neuralink.com/ ## Derived Section ### Condition Browse Module - Ancestors - ID: D000013118 - Term: Spinal Cord Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000020196 - Term: Trauma, Nervous System - ID: D000014947 - Term: Wounds and Injuries - ID: D000019636 - Term: Neurodegenerative Diseases - ID: D000009468 - Term: Neuromuscular Diseases - ID: D000057177 - Term: TDP-43 Proteinopathies - ID: D000057165 - Term: Proteostasis Deficiencies - ID: D000008659 - Term: Metabolic Diseases - ID: D000009461 - Term: Neurologic Manifestations ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M15916 - Name: Spinal Cord Injuries - Relevance: HIGH - As Found: Spinal Cord Injury - ID: M15415 - Name: Sclerosis - Relevance: LOW - As Found: Unknown - ID: M18879 - Name: Motor Neuron Disease - Relevance: HIGH - As Found: Lateral Sclerosis - ID: M4024 - Name: Amyotrophic Lateral Sclerosis - Relevance: HIGH - As Found: Amyotrophic Lateral Sclerosis - ID: M13157 - Name: Paralysis - Relevance: HIGH - As Found: Paralysis - ID: M14632 - Name: Quadriplegia - Relevance: HIGH - As Found: Quadriplegia - ID: M15915 - Name: Spinal Cord Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown - ID: M22023 - Name: Trauma, Nervous System - Relevance: LOW - As Found: Unknown - ID: M21558 - Name: Neurodegenerative Diseases - Relevance: LOW - As Found: Unknown - ID: M12411 - Name: Neuromuscular Diseases - Relevance: LOW - As Found: Unknown - ID: M28759 - Name: TDP-43 Proteinopathies - Relevance: LOW - As Found: Unknown - ID: M28747 - Name: Proteostasis Deficiencies - Relevance: LOW - As Found: Unknown - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: T4699 - Name: Primary Lateral Sclerosis - Relevance: LOW - As Found: Unknown - ID: T349 - Name: Amyotrophic Lateral Sclerosis - Relevance: HIGH - As Found: Amyotrophic Lateral Sclerosis ### Condition Browse Module - Meshes - ID: D000013119 - Term: Spinal Cord Injuries - ID: D000016472 - Term: Motor Neuron Disease - ID: D000000690 - Term: Amyotrophic Lateral Sclerosis - ID: D000010243 - Term: Paralysis - ID: D000011782 - Term: Quadriplegia ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429722 **Brief Title:** To Evaluate the Effects of NMRA-335140 on Symptoms of Major Depression in Participants With Bipolar II Disorder. **Official Title:** A Phase 2a, Randomized, Double-blind, Placebo-controlled Pilot Study to Evaluate the Effects of Oral NMRA-335140 Versus Placebo in Participants With a Major Depressive Episode Associated With Bipolar II Disorder #### Organization Study ID Info **ID:** NMRA-335140-202 #### Organization **Class:** INDUSTRY **Full Name:** Neumora Therapeutics, Inc. ### Status Module #### Completion Date **Date:** 2025-12 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-21 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2025-12 **Type:** ESTIMATED #### Start Date **Date:** 2024-05-13 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Neumora Therapeutics, Inc. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Oversight Has DMC:** True ### Description Module **Brief Summary:** This is a randomized, double-blind, placebo-controlled pilot study aiming to evaluate the effects of NMRA-335140 on symptoms of major depression in adults with Bipolar (BP) II disorder. The study design consists of a Screening Period (up to 28 days), a 6-week Treatment Period (during which participants will receive either NMRA-335140 or placebo), and a 6-week Safety Follow-up Period. ### Conditions Module **Conditions:** - Major Depressive Episode Associated With Bipolar II Disorder **Keywords:** - NMRA-335140 - Navacaprant - BTRX-335140 - CYM-53093 - Bipolar II Disorder - Major Depressive Episode - Placebo-controlled - Double-blind ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** QUADRUPLE **Masking Description:** Sponsor will also be blinded **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 60 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants will receive a NMRA-335140 tablet at a dose of 80 mg QD. **Intervention Names:** - Drug: NMRA-335140 80 mg **Label:** NMRA-335140 80 milligrams (mg) once daily (QD) **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Placebo participants will receive matching placebo tablet once daily. **Intervention Names:** - Drug: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - NMRA-335140 80 milligrams (mg) once daily (QD) **Description:** Participants will receive NMRA-335140 at a dose of 80 mg QD, orally. **Name:** NMRA-335140 80 mg **Other Names:** - BTRX-335140 - CYM-53093 - Navacaprant **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** Placebo will be administered orally **Name:** Placebo **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The MADRS is a 10-item, clinician-rated scale that evaluates the participant's depressive symptomatology during the past week. Participants are rated on items assessing feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty in concentration, and lack of interest. Each item will be scored on a 7- point scale with a score of 0 reflecting no symptoms and a score of 6 reflecting symptoms of maximum severity. Thus, scores in the MADRS range from 0 to 60, with increasing scores indicating increasing severity. **Measure:** Change from Baseline to Week 6 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score **Time Frame:** Baseline and up to Week 6 #### Secondary Outcomes **Description:** The SHAPS is a 14-item participant-reported instrument which measures anhedonia. It has been shown to be valid and reliable in normal and clinical samples, with adequate construct validity, satisfactory test-retest reliability, and high internal consistency. The scale will be completed by the participant and reviewed by site personnel qualified to oversee completeness. Each of the 14 items has a set of 4 responses, 2 of which endorse agreement (Definitely Agree, Agree) and 2 of which endorse disagreement (Disagree, Strongly Disagree). A total score can be derived by summing the response items; where those answered with "strongly agree" will be coded as a 1, while a "strongly disagree" response will be coded as 4. Therefore, scores on the SHAPS can range from 14 to 56, with higher scores corresponding to higher levels of anhedonia. **Measure:** Change from Baseline to Week 6 assessed in the Snaith-Hamilton Pleasure Scale (SHAPS) total score **Time Frame:** Baseline and up to Week 6 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Have a primary Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revised (DSM-5-TR) diagnosis of BP II disorder with a current major depressive episode (MDE), without psychotic features confirmed by Structured Clinical Interview for DSM 5 Disorders, Clinical Trials Version (SCID-5-CT) at screening (this may be a first or recurrent episode). 2. Participant's current MDE and lifetime history of hypomanic episodes must be confirmed by independent assessment. 3. The symptoms of the current MDE have been present for more than 4 weeks prior to the Screening Visit, but no longer than 12 months prior to the Screening Visit. 4. Have a MADRS total score of 25 or higher at Screening and Baseline. 5. A change in MADRS total score between Screening and Baseline of ≤20%. Exclusion Criteria: 1. Have failed 2 or more courses of antidepressant (adequate dose and duration, i.e., minimum 6 weeks) or mood stabilizer/antipsychotic treatment (each or in combination) for treatment of depressive symptoms in the current MDE. 2. Have currently or in the past year any of the following DSM-5-TR disorders: bipolar episodes with mixed features (including the current MDE), bipolar II with rapid cycling pattern (4 or more distinct mood episodes during a 12-month period). Participants with comorbid generalized anxiety disorder, social anxiety disorder, simple phobias, panic disorder, for whom bipolar II MDE is considered the primary diagnosis are not excluded. 3. Have a lifetime diagnosis of bipolar I disorder (manic episode schizophrenia, schizoaffective disorder, schizophreniform disorder, anorexia nervosa, bulimia nervosa, cluster B personality disorder, post-traumatic stress disorder (PTSD), or obsessive- compulsive disorder. 4. Have moderate to severe substance or alcohol use disorder, per DSM-5-TR criteria, within the 12 months prior to screening (excluding nicotine). 5. Are actively suicidal (e.g., any suicide attempts within the past 12 months) or are at serious suicidal risk as indicated by any current suicidal intent, including a plan, as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) (score of "YES" on suicidal ideation Item 4 or 5 within 3 months prior to Visit 1 \[screening\]) and/or based on clinical evaluation by the Investigator; or are homicidal, in the opinion of the Investigator. Note: Other protocol defined Inclusion/Exclusion criteria may apply. **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Study Contact **Role:** CONTACT #### Locations **Location 1:** **City:** Lauderhill **Country:** United States **Facility:** Neumora Investigator Site **State:** Florida **Status:** RECRUITING **Zip:** 33161 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001526 - Term: Behavioral Symptoms - ID: D000019964 - Term: Mood Disorders - ID: D000001523 - Term: Mental Disorders ### Condition Browse Module - Browse Branches - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M7061 - Name: Depressive Disorder - Relevance: HIGH - As Found: Depressive Episode - ID: M7058 - Name: Depression - Relevance: HIGH - As Found: Depressive Episode - ID: M7060 - Name: Depressive Disorder, Major - Relevance: HIGH - As Found: Major Depressive Episode - ID: M4818 - Name: Behavioral Symptoms - Relevance: LOW - As Found: Unknown - ID: M21835 - Name: Mood Disorders - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003863 - Term: Depression - ID: D000003866 - Term: Depressive Disorder - ID: D000003865 - Term: Depressive Disorder, Major ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429709 **Brief Title:** Utility of Advanced Ultrasound Otoscope In The Diagnosis of AOM **Official Title:** Utility of Advanced Ultrasound Otoscope In The Diagnosis of Acute Otitis Media #### Organization Study ID Info **ID:** H-50018 #### Organization **Class:** OTHER **Full Name:** Baylor College of Medicine ### Status Module #### Completion Date **Date:** 2024-08 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-23 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-08 **Type:** ESTIMATED #### Start Date **Date:** 2021-09-01 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-04-16 **Study First Submit QC Date:** 2024-05-23 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** OtoNexus Medical Technologies, Inc. #### Lead Sponsor **Class:** OTHER **Name:** Baylor College of Medicine #### Responsible Party **Investigator Affiliation:** Baylor College of Medicine **Investigator Full Name:** Yi-Chun Carol Liu **Investigator Title:** Associate Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The objective of this study is to collect ultrasound signal information and visual otoscopic images with an engineering prototype device for children scheduled for tympanostomy tube surgery for the purpose of algorithm development. **Detailed Description:** The objective of this study is to collect ultrasound signal information and visual otoscopic images with an engineering prototype device for children scheduled for tympanostomy tube surgery for the purpose of algorithm development. After informed consent from a parent or guardian is obtained, ultrasound and visual data will be collected for each of the child's ears. The images will be taken with the Advanced Ultrasound Otoscope device. The ear laterality will be noted as well as any infection present in the fluid, non-infected fluid, or normal findings in the middle ear as reported by the surgeon. No identifiable data will be recorded. Each study participant will be given a unique study number that will be linked to the images and middle ear findings. No additional information is gathered including age, sex, name or other PHI. The images and corresponding study data will be stored on a password protected smartphone or tablet as well as on a password protected external hard drive. Other characteristics that will be collected include surgical and lab findings regarding effusion, presence or absence (i.e. effusion). The middle ear fluid which is usually suctioned will be collected in a trap chamber- Tympap- and this collected fluid will be sent to the microbiology laboratory for analysis Investigators will be collecting ultrasound and visual data from the tympanic membrane. The images the investigators are collecting are optical images of the surface of the tympanic membrane. The waveforms do not traverse the body tissue, the tympanic membrane is a strong reflector, and the signal is returned to the ultrasound transducer for processing the waveform from an analog to a digital signal. The power of the ultrasound signal is 1/1000th of the ultrasound power used for fetal imaging which is considered safe. ### Conditions Module **Conditions:** - Otitis Media Recurrent - Middle Ear Infection - Ear Infection **Keywords:** - Otoscope - Tympanogram - Effusion - Ultrasound ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 300 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Ultrasound and signal information and visual otoscopic images will be collected with an engineering prototype otoscope device for children scheduled for tympanostomy tube surgery. Images of each of the child's ears will be taken by the advanced ultrasound otoscope device. Data collected will include ear laterality, surgical and lab findings of the effusion (present or absent) and characteristics as reported by the surgeon. The middle ear fluid which is usually suctioned will be collected in a trap chamber- Tympap- and this collected fluid will be send for analysis to microbiology. The pathology results will be recorded to correlate ultrasound signals to surgical findings **Intervention Names:** - Device: Advanced Ultrasound Otoscope **Label:** Algorithm Development #### Arm Group 2 **Description:** The clinical validation phase includes the same procedures as the algorithm development phase only, the clinical validation phase is a double blind study where ultrasound score is compared to surgical findings and lab analysis. **Intervention Names:** - Device: Advanced Ultrasound Otoscope **Label:** Clinical Validation ### Interventions #### Intervention 1 **Arm Group Labels:** - Algorithm Development - Clinical Validation **Description:** The Advanced Ultrasound Otoscope is a tool for visualization of the human tympanic membrane and detection of middle ear effusion type **Name:** Advanced Ultrasound Otoscope **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Correlation of device measurements to the gold standard of surgeon's findings at myringotomy. Gather ultrasound data for the four disease states of middle ear effusion (normal, viral infection, bacterial infection, and Adhesive Otitis Media) and correlate the ultrasound waveforms with the surgeon's findings and lab analysis obtained at tympanostomy tube insertion. For estimation of fluid character, the middle ear fluid will be correlated with the surgeon's semiquantitative grading of middle ear fluid. For the analysis of microbiota, the middle ear effusion fluid will be sent to microbiology. **Measure:** Device Performance **Time Frame:** 2 years and 6 months #### Secondary Outcomes **Description:** Evaluate the usability of the Advanced Ultrasound Otoscope device in pediatric patients as measured by the ability of the device to fit in subjects' external auditory canals and obtain a tympanic mobility measurement(s). **Measure:** Device Usability **Time Frame:** 1 year ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Newborn to 12 years of age * Receiving first set of pressure equalization (PE) tubes, even if coordinated with other procedures such as adenoidectomy * Indication for surgery includes recurrent acute otitis media, chronic otitis media with effusion, Eustachian tube dysfunction, and/or hearing loss. Exclusion Criteria: * Cholesteatoma, tympanic membrane perforation, myringitis * History of PE tube placement or PE tubes currently in place. **Maximum Age:** 12 Years **Minimum Age:** 0 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD **Study Population:** We will be recruiting patients between 0 months and 12 years of age who meet the listed inclusion criteria and do not meet any of the listed exclusion criteria. We are not selecting patients based on race/ethnicity or gender/sex. Parents must be fluent in either English or Spanish. ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Rachel Arp **Phone:** 936-267-7707 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Justine Kasay **Role:** CONTACT #### Locations **Location 1:** **City:** Houston **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Rachel Arp - **Phone:** 936-267-7707 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Justine Kasay - **Role:** CONTACT ***Contact 3:*** - **Name:** Yi-Chun Liu, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** Texas Children's Hospital **State:** Texas **Status:** RECRUITING **Zip:** 77030 #### Overall Officials **Official 1:** **Affiliation:** Baylor College of Medicine **Name:** Tiffany Raynor, MD **Role:** STUDY_CHAIR **Official 2:** **Affiliation:** Baylor College of Medicine **Name:** Yi-Chun Liu, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 3:** **Affiliation:** Baylor College of Medicine **Name:** Shraddha Mukerji, MD **Role:** STUDY_CHAIR **Official 4:** **Affiliation:** Baylor College of Medicine **Name:** Jennifer Yan, MD **Role:** STUDY_CHAIR **Official 5:** **Affiliation:** Baylor College of Medicine **Name:** Sonal Saraiya, MD **Role:** STUDY_CHAIR **Official 6:** **Affiliation:** Baylor College of Medicine **Name:** Mary E Williamson, MD **Role:** STUDY_CHAIR **Official 7:** **Affiliation:** Baylor College of Medicine **Name:** Henri Traboulsi, MD **Role:** STUDY_CHAIR **Official 8:** **Affiliation:** Baylor College of Medicine **Name:** Anna Messner, MD **Role:** STUDY_CHAIR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes - ID: D000004427 - Term: Ear Diseases - ID: D000010038 - Term: Otorhinolaryngologic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC01 - Name: Infections - Abbrev: BC09 - Name: Ear, Nose, and Throat Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M14850 - Name: Recurrence - Relevance: LOW - As Found: Unknown - ID: M10283 - Name: Infections - Relevance: HIGH - As Found: Infection - ID: M6368 - Name: Communicable Diseases - Relevance: HIGH - As Found: Infection - ID: M12954 - Name: Otitis - Relevance: HIGH - As Found: Ear Infection - ID: M12956 - Name: Otitis Media - Relevance: HIGH - As Found: Otitis Media - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown - ID: M7601 - Name: Ear Diseases - Relevance: LOW - As Found: Unknown - ID: M12961 - Name: Otorhinolaryngologic Diseases - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007239 - Term: Infections - ID: D000003141 - Term: Communicable Diseases - ID: D000010031 - Term: Otitis - ID: D000010033 - Term: Otitis Media ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429696 **Brief Title:** PD-L1 Inhibitor Combined With Apatinib as First-line Maintenance Treatment for Extensive-stage Small Cell Lung Cancer **Official Title:** Single-arm, Prospective Clinical Study of PD-L1 Inhibitor Combined With Apatinib as First-line Maintenance Treatment for Extensive-stage Small Cell Lung Cancer #### Organization Study ID Info **ID:** NFEC-2024-220 #### Organization **Class:** OTHER **Full Name:** Nanfang Hospital, Southern Medical University ### Status Module #### Completion Date **Date:** 2026-04-30 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-21 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2026-04-30 **Type:** ESTIMATED #### Start Date **Date:** 2024-05-14 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Nanfang Hospital, Southern Medical University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** This is a prospective, single-arm clinical study designed to evaluate the 6-month progression-free survival rate (6-month PFS rate) of a PD-L1 inhibitor combined with apatinib as first-line maintenance treatment for extensive-stage small cell lung cancer (ES-SCLC). The study plans to recruit 40 patients. After receiving 4-6 cycles of induction therapy, patients whose efficacy is evaluated as CR, PR or SD (according to RECIST 1.1) will enter maintenance therapy with PD-L1 inhibitor + apatinib 250 mg po qd. , the selection of PD-L1 inhibitors in the maintenance phase is consistent with the first-line standard treatment in the induction phase. Efficacy was assessed using RECISIT 1.1, with imaging evaluations every 6 weeks (±7 days) for 48 weeks after the first dose and every 9 weeks (±7 days) after week 48, regardless of treatment delays or interruptions, until Disease progression or study termination, whichever occurs first. The primary efficacy endpoint of this study is 6-month PFS rate, and secondary efficacy endpoints include median PFS, median OS and safety. ### Conditions Module **Conditions:** - Small Cell Lung Cancer Extensive Stage **Keywords:** - first-line maintenance treatment - PD-L1 inhibitor - apatinib - ES-SCLC ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 40 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Six-month progression-free survival rate (6-month PFS rate) of PD-L1 inhibitor combined with apatinib in first-line maintenance treatment of extensive-stage small cell lung cancer (ES-SCLC) **Intervention Names:** - Drug: PD-L1 inhibitor combined with apatinib **Label:** PD-L1 inhibitor combined with apatinib **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - PD-L1 inhibitor combined with apatinib **Description:** Every 3 weeks (21 days) is a treatment cycle. After 4-6 cycles of induction therapy, patients whose efficacy is evaluated as CR, PR or SD (according to RECIST 1.1) will enter maintenance therapy until the disease progresses and becomes intolerable. Toxic and side effects, death, withdrawal of information or the investigator's decision to withdraw the subject from the study, non-compliance with study treatment or other reasons specified in the study procedures or protocol, or treatment for up to 2 years. Maintenance treatment: PD-L1 inhibitor + apatinib 250 mg po qd, maintained for up to 2 years. Note: The specific PD-L1 inhibitor is selected by the researcher, such as adebelimab 1200mg iv, q3w; or atezolizumab 1200mg iv d1, q3w; or durvalumab 1500mg iv d1, q3w . The selection of PD-L1 inhibitors in the maintenance phase is consistent with the first-line standard treatment in the induction phase. **Name:** PD-L1 inhibitor combined with apatinib **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Defined as the time between the onset of PD when the patient first received study drug and death, whichever occurred first. **Measure:** 6-month progression-free survival (PFS) **Time Frame:** 2 years #### Secondary Outcomes **Description:** Defined as the time between the onset of PD when the patient first received study drug and death, whichever occurred first. **Measure:** Median progression-free survival (PFS) **Time Frame:** 3 years **Description:** Defined as the time between the patient's first receipt of study drug and death **Measure:** Median overall survival (OS) **Time Frame:** 3 years **Description:** Defined as the proportion of patients achieving complete response (CR) or partial response (PR). **Measure:** Objective response rate (ORR) **Time Frame:** 3 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Aged 18-75 years old, both men and women are welcome; 2. Extensive-stage small cell lung cancer confirmed by histology or cytology (staging according to the American Veterans Lung Cancer Association, VALG); 3. Patients whose induction therapy must receive the first-line standard treatment regimen of PD-L1 monoclonal antibody combined with chemotherapy, and whose efficacy evaluation is CR, PR or SD (according to RECIST 1.1); patients who have previously undergone surgical treatment and receive curative adjuvant therapy such as radiotherapy , chemotherapy patients, there is a treatment-free interval of at least 6 months from the last chemotherapy, radiotherapy or chemoradiotherapy to the diagnosis of extensive-stage SCLC; 4. Expected survival time ≥12 weeks; 5. ECOG physical status score 0\~1 points; 6. Before the first dose of study drug, laboratory test values must meet the following conditions: 1. Blood routine (no blood transfusion or correction with hematopoietic stimulating factor drugs within 14 days before screening): WBC ≥3.0 × 109/L; ANC ≥1.5 × 109/L; PLT ≥100 × 109/L; HGB ≥90 g/L; 2. Liver function: AST ≤2.5 × ULN in subjects without liver metastasis; ALT ≤2.5 × ULN; ALT and AST in subjects with liver metastasis ≤5 × ULN; TBIL ≤1.5 × ULN; 3. Renal function: serum Cr ≤1.5 × ULN or CrCl ≥50 mL/min (using Cockcroft/Gault formula); 4. Coagulation function: INR ≤1.5 × ULN, APTT ≤1.5 × ULN (only applicable to patients who are not currently receiving anticoagulation therapy); 7. Women of childbearing age must have a serum pregnancy test within 7 days before taking the drug for the first time, and the result is negative. Female subjects of childbearing age and male subjects whose partners are women of childbearing age must agree to use contraception within 24 weeks from signing the informed consent form to the last administration of the study drug; 8. The subjects voluntarily joined this study, signed the informed consent form, had good compliance, and cooperated with the follow-up. Exclusion Criteria: 1. Patients transformed from non-small cell carcinoma (NSCLC) to SCLC or SCLC with mixed histology; 2. Meningeal metastasis or symptomatic central nervous system metastasis; for patients with asymptomatic brain metastasis or stable symptoms for ≥ 2 weeks after treatment of brain metastasis, they can participate in this study as long as they meet all the following criteria: Outside the central nervous system Have measurable lesions, no metastasis to the meninges, midbrain, pons, cerebellum, medulla oblongata or spinal cord, no previous history of intracranial hemorrhage, and stop hormone therapy 14 days before the first dose of study drug; 3. Third space effusion with clinical symptoms requires repeated drainage, such as pericardial effusion, pleural effusion and peritoneal effusion that cannot be controlled by pumping or other treatments; 4. Have a history of idiopathic pulmonary fibrosis, organizing pneumonia (such as bronchiolitis obliterans), drug-induced pneumonia, infectious pneumonia, radiation pneumonitis requiring steroid treatment, active tuberculosis, or other serious effects on the lungs Functional moderate to severe lung disease; 5. There is an active autoimmune disease and corticosteroids (\>10 mg/day prednisone or equivalent dose) or other immunosuppressants are used within 14 days before the first medication; 6. Have serious cardiovascular diseases, such as New York Heart Association (NYHA) grade 2 or above heart failure, unstable angina, unstable arrhythmia, and myocardial infarction occurring within 3 months before enrollment or cerebrovascular accident; 7. Other malignant tumors ≤5 years before the first dose of medication (fully treated cervical carcinoma in situ, basal cell or squamous epithelial cell skin cancer, localized prostate cancer after radical surgery, and ductal carcinoma in situ after radical surgery can be admitted) group and allows hormone therapy for non-metastatic prostate or breast cancer); 8. Hypertension that cannot be controlled by oral antihypertensive drugs (systolic blood pressure ≧140mmHg or diastolic blood pressure ≧90mmHg); 9. Urine routine shows urine protein ≥++ and confirms that the 24-hour urine protein quantification is \>1.0 g; 10. Risk of bleeding: Have clinically significant bleeding symptoms or clear bleeding tendency within 3 months before enrollment, such as gastrointestinal bleeding, bleeding gastric ulcer, etc.; suffer from hereditary or acquired bleeding diseases or coagulation Functional disorders, such as aplastic anemia, etc.; taking anticoagulant or antiplatelet drugs (such as warfarin, phenprocoumon); 11. Those who have recently experienced intestinal obstruction or gastrointestinal perforation (within 3 months); or those who are unable to swallow tablets normally, which may affect drug absorption as judged by the researcher; 12. People with the following infectious diseases are not allowed to join the group: 1. HBsAg is positive and the HBV DNA copy number is greater than the upper limit of normal value (1000 copies/ml or 500IU/ml) in the laboratory of the research center; 2. HCV positive (HCV RNA or HCV Ab detection indicates acute or chronic infection); 3. Known history of HIV positivity or known acquired immunodeficiency syndrome; 13. Have undergone major surgery within 28 days before the screening period, or plan to undergo major surgery during the study period; 14. Have received systemic immunosuppressive drug treatment (including but not limited to glucocorticoids, cyclophosphamide, azathioprine, methotrexate, thalidomide and anti-tumor necrosis factor \[anti-tumor necrosis factor\] within 1 week before the first medication) TNF\] drugs). Patients receiving short-term, systemic immunosuppressive therapy, such as glucocorticoids for nausea, vomiting, or allergic reaction management or prophylaxis, may be enrolled in the study after approval by the investigator; 15. Live attenuated vaccines are used within 28 days before the first dose, or live attenuated vaccines are expected to be needed during the study; 16. Known to be allergic to study drugs or excipients, known to have severe allergic reactions to any monoclonal antibody drug; 17. Have received any other experimental drug treatment or participated in another interventional clinical study within 4 weeks before the first use of the drug; 18. Patients who have previously received allogeneic bone marrow transplantation or solid organ transplantation; 19. According to the researcher's judgment, the subject has other factors that may lead to the forced termination of this study, such as non-compliance with the protocol, other serious diseases (including mental illness) that require combined treatment, and family or social factors that may affect the study. to the safety of subjects or the collection of information and samples **Maximum Age:** 75 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Wangjun Liao, MD, PhD **Phone:** 86-20-62787731 **Role:** CONTACT #### Overall Officials **Official 1:** **Affiliation:** Nanfang Hospital, Southern Medical University **Name:** Wangjun Liao, MD, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012142 - Term: Respiratory Tract Neoplasms - ID: D000013899 - Term: Thoracic Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases - ID: D000002283 - Term: Carcinoma, Bronchogenic - ID: D000001984 - Term: Bronchial Neoplasms ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M11172 - Name: Lung Neoplasms - Relevance: HIGH - As Found: Lung Cancer - ID: M28323 - Name: Small Cell Lung Carcinoma - Relevance: HIGH - As Found: Small Cell Lung Cancer - ID: M5534 - Name: Carcinoma - Relevance: LOW - As Found: Unknown - ID: M14979 - Name: Respiratory Tract Neoplasms - Relevance: LOW - As Found: Unknown - ID: M16658 - Name: Thoracic Neoplasms - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: M5540 - Name: Carcinoma, Bronchogenic - Relevance: LOW - As Found: Unknown - ID: M5260 - Name: Bronchial Neoplasms - Relevance: LOW - As Found: Unknown - ID: T5271 - Name: Small Cell Lung Cancer - Relevance: HIGH - As Found: Small Cell Lung Cancer ### Condition Browse Module - Meshes - ID: D000008175 - Term: Lung Neoplasms - ID: D000055752 - Term: Small Cell Lung Carcinoma ### Intervention Browse Module - Ancestors - ID: D000000970 - Term: Antineoplastic Agents - ID: D000047428 - Term: Protein Kinase Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000074322 - Term: Antineoplastic Agents, Immunological ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M272500 - Name: Durvalumab - Relevance: LOW - As Found: Unknown - ID: M349417 - Name: Atezolizumab - Relevance: LOW - As Found: Unknown - ID: M288166 - Name: Apatinib - Relevance: HIGH - As Found: HER2 - ID: M2342 - Name: Immune Checkpoint Inhibitors - Relevance: HIGH - As Found: DOX - ID: M25820 - Name: Protein Kinase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: M1346 - Name: Antineoplastic Agents, Immunological - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000553458 - Term: Apatinib - ID: D000082082 - Term: Immune Checkpoint Inhibitors ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429683 **Brief Title:** Effectıveness of The Sexually Transmıtted Dıseases Educatıon Program for Adolescents **Official Title:** Effectıveness of The Sexually Transmıtted Dıseases Educatıon Program for Adolescents #### Organization Study ID Info **ID:** IstanbulGelisimuniversity #### Organization **Class:** OTHER **Full Name:** Istanbul Gelisim University ### Status Module #### Completion Date **Date:** 2023-06-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-23 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2023-02-01 **Type:** ACTUAL #### Start Date **Date:** 2022-10-01 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-17 **Study First Submit QC Date:** 2024-05-23 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Bahar Nur Kanbur #### Responsible Party **Investigator Affiliation:** Istanbul Gelisim University **Investigator Full Name:** Bahar Nur Kanbur **Investigator Title:** Assistant Professor **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The World Health Organization has defined the period between the ages of 10-19 as adolescence, 15-24 years as youth and 10-24 years as youth period. Adolescence is divided into 3 periods: early adolescence (10-13 years), middle adolescence (14-16 years) and late adolescence (17-21 years). HIV virus and AIDS, which have become a problem among sexually transmitted diseases all over the world, have increased the importance of controlling sexually transmitted diseases. There is a strong correlation between the spread of STDs through traditional means and the transmission of HIV; and sexually transmitted diseases have been found to increase the risk of sexual transmission of HIV. According to WHO data, 340 million treatable STDs, millions of incurable STDs and 5 million HIV cases occur worldwide each year. **Detailed Description:** People in the 15-49 age group who are sexually active are the most likely to contract sexually transmitted diseases. The prevalence of STDs is higher in developing countries than in developed countries. These diseases are among the top 5 etiologic factors that cause loss of years of "healthy productive life" in developing countries. As in other countries, sexually transmitted diseases are of great importance in terms of complications and sequelae in Turkey One out of 20 young people is infected with STDs every year. In our country, the age of sexual maturation has shifted earlier. In addition, the age of sexual experience of young people has also shifted earlier. Young people's understanding of freedom and their inability to access FP methods whenever they want negatively affect their sexual health behaviors. Impact on Society STDs cause a lot of economic and social damage to society. STDs may disrupt the normal functioning of family, community and health institutions and leave these institutions under a heavy economic burden. STDs reduce the productivity of men and women at the most productive ages of their lives. In addition, when outbreaks of these infections are not controlled, the costs to society will increase. Translated with DeepL.com (free version) ### Conditions Module **Conditions:** - Sexually Transmitted Diseases **Keywords:** - adolescent - sexually transmitted diseases - education ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 250 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** To evaluate the effectiveness of sexually transmitted diseases education given to young adolescents aged 17-21 years **Intervention Names:** - Other: Sexually transmitted diseases training for young adolescents aged 17-21 **Label:** Sexually transmitted diseases training for young adolescents aged 17-21 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Sexually transmitted diseases training for young adolescents aged 17-21 **Description:** Education **Name:** Sexually transmitted diseases training for young adolescents aged 17-21 **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** The Sexually Transmitted Diseases Knowledge Test includes 36 questions that assess students' level of knowledge about sexually transmitted diseases. The questions are answered as "True", "False", and "I don't know". Students will be administered the STD knowledge test before the training. The test will be administered again after the training. In the post-training test, the student is expected to give more correct answers to the questions compared to the previous test. **Measure:** Students' Knowledge Test on Sexually Transmitted Diseases **Time Frame:** 2 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * At a Foundation University located within the borders of Istanbul Province 1.2.3. and 4th grade students Exclusion Criteria: - **Healthy Volunteers:** True **Maximum Age:** 21 Years **Minimum Age:** 17 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Istanbul **Country:** Turkey **Facility:** Istanbul Gelisim University **State:** Avcılar #### Overall Officials **Official 1:** **Affiliation:** Trakya University **Name:** Canan Örüklü **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000003141 - Term: Communicable Diseases - ID: D000007239 - Term: Infections - ID: D000091662 - Term: Genital Diseases - ID: D000091642 - Term: Urogenital Diseases - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M15558 - Name: Sexually Transmitted Diseases - Relevance: HIGH - As Found: Sexually Transmitted Diseases - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M2876 - Name: Genital Diseases - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000012749 - Term: Sexually Transmitted Diseases ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429670 **Acronym:** VENAURA **Brief Title:** Real World Use of Azacitidine and Venetoclax in Acute Myeloid Leukemia in Frontline and Relapse/Refractory **Official Title:** Real World Use of Azacitidine and Venetoclax in Acute Myeloid Leukemia in Frontline and Relapse/Refractory Settings: a Multicentric Study From French AURAML Group #### Organization Study ID Info **ID:** 69HCL24_0521 #### Organization **Class:** OTHER **Full Name:** Hospices Civils de Lyon ### Status Module #### Completion Date **Date:** 2023-09-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-23 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2023-07-01 **Type:** ACTUAL #### Start Date **Date:** 2023-05-01 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-13 **Study First Submit QC Date:** 2024-05-23 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Hospices Civils de Lyon #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Azacytidine and venetoclax combination regimen (AZA/VEN) is the standard of care in frontline acute myeloid leukemia (AML) settings for unfit to intensive chemotherapy patients. AZA/VEN combination regiment was approved in France in 2021 but was already used in outlabel fashion since 2019. However, AZA/VEN is also associated with an increased hematological toxicity compared to azacytidine alone. In this context, alternative AZA/VEN regimens emerged progressively based on each physician experience and local procedures. Moreover, AZA/VEN is also recognized as a valuable therapeutic option in relapse/refractory settings. In this multicentric study, the investigators aimed to evaluate the efficacy and safety of various AZA/VEN regimen in frontline and relapse/refractory (R/R) patients diagnosed with AML in real life setting. The investigators will retrospectively analyze clinical outcome of patients from 11 different French centers (Saint-Etienne, Clermont-Ferrand, Lyon (Hopital Lyon Sud, Centre Léon Bérard), Vichy, Annecy, Chambery, Valence, Bourgoin-Jallieu, Grenoble, Roanne) in Auvergne Rhône Alpes (AURA) region, between January 2019 and December 2023. Composite complete remission was defined as in VIALE-A trial. Measurable residual disease (MRD) negativity was defined as ≤ 10-3 by flow cytometry (on bone marrow) and/or ≤ 10-4 for NPM1 by RT-qPCR. ### Conditions Module **Conditions:** - Acute Myeloid Leukemia **Keywords:** - acute myeloid leukemia - azacitdine - venetoclax - MRD ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** RETROSPECTIVE #### Enrollment Info **Count:** 500 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Adult patients with acute myeloid leukemia treated by AZACYTIDINE and VENETOCLAX in frontline and relapse/refractory settings **Label:** Azacytidine and venetoclax treated patients ### Outcomes Module #### Primary Outcomes **Description:** Overall survival corresponds to time to death from the initiaiton of AZA/VEN, regardless of disease recurrence. **Measure:** Overall survival **Time Frame:** up to 5 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * \>18 years old * Acute myeloid leukemia patients at diagnostic, in relapse/refractory settings, or MRD relapse. * receiving AZA/VEN combination regimen Exclusion Criteria: * Another VEN combination chemotherapy * AZA/VEN initiation prior January 2019 and after December 2023 * Opposition to the study **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Every adult patients ( \>18 years old) with a diagnostic of AML treated by the association of AZACYTIDINE and VENETOCLAX between January 2019 and December 2023. ### Contacts Locations Module #### Locations **Location 1:** **City:** Bourgoin-Jallieu **Country:** France **Facility:** Centre Hospitalier Pierre Oudot | Groupement hospitalier Nord **Zip:** 38300 **Location 2:** **City:** Chambéry **Country:** France **Facility:** METROPOLE SAVOIE - SITE CHAMBERY, place Lucien Biset, **Zip:** 73000 **Location 3:** **City:** Clermont-Ferrand **Country:** France **Facility:** CHU Clermont-Ferrand Site Estaing **Zip:** 63100 **Location 4:** **City:** La Tronche **Country:** France **Facility:** CHU Grenoble Alpes **Location 5:** **City:** Lyon **Country:** France **Facility:** Centre Léon Bérard **Zip:** 69003 **Location 6:** **City:** Lyon **Country:** France **Facility:** Hospices Civils de Lyon **Zip:** 69229 **Location 7:** **City:** Roanne **Country:** France **Facility:** Centre Hospitalier de Roanne **Zip:** 42300 **Location 8:** **City:** Saint-Priest-en-Jarez **Country:** France **Facility:** CHU de Saint-Étienne Hôpital Nord **Zip:** 42270 **Location 9:** **City:** Valence **Country:** France **Facility:** Centre Hospitalier de Valence **Zip:** 26000 **Location 10:** **City:** Valence **Country:** France **Facility:** Ch de Valence **Location 11:** **City:** Vichy **Country:** France **Facility:** Hopital Vichy **Zip:** 03200 **Location 12:** **City:** Épagny **Country:** France **Facility:** Centre Hospitalier Annecy Genevois **Zip:** 74370 ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000006402 - Term: Hematologic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10945 - Name: Leukemia - Relevance: HIGH - As Found: Leukemia - ID: M10955 - Name: Leukemia, Myeloid - Relevance: HIGH - As Found: Myeloid Leukemia - ID: M18127 - Name: Leukemia, Myeloid, Acute - Relevance: HIGH - As Found: Acute Myeloid Leukemia - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M9490 - Name: Hematologic Diseases - Relevance: LOW - As Found: Unknown - ID: T3995 - Name: Myeloid Leukemia - Relevance: HIGH - As Found: Myeloid Leukemia - ID: T182 - Name: Acute Myeloid Leukemia - Relevance: HIGH - As Found: Acute Myeloid Leukemia - ID: T188 - Name: Acute Non Lymphoblastic Leukemia - Relevance: HIGH - As Found: Acute Myeloid Leukemia - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007938 - Term: Leukemia - ID: D000007951 - Term: Leukemia, Myeloid - ID: D000015470 - Term: Leukemia, Myeloid, Acute ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M249656 - Name: Venetoclax - Relevance: LOW - As Found: Unknown - ID: M4673 - Name: Azacitidine - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429657 **Acronym:** Ketamine **Brief Title:** Ketamine for Sedation in Severe Traumatic Brain Injury **Official Title:** Ketamine for Sedation in Severe Traumatic Brain Injury #### Organization Study ID Info **ID:** C.2024.025 #### Organization **Class:** OTHER **Full Name:** Henry M. Jackson Foundation for the Advancement of Military Medicine ### Status Module #### Completion Date **Date:** 2027-06-30 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-23 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2027-01-01 **Type:** ESTIMATED #### Start Date **Date:** 2024-06-01 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-04-16 **Study First Submit QC Date:** 2024-05-23 ### Sponsor Collaborators Module #### Collaborators **Class:** FED **Name:** Uniformed Services University of the Health Sciences **Class:** FED **Name:** Brooke Army Medical Center #### Lead Sponsor **Class:** OTHER **Name:** Henry M. Jackson Foundation for the Advancement of Military Medicine #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Is US Export:** True **Oversight Has DMC:** False ### Description Module **Brief Summary:** This protocol is for an open-label randomized trial evaluating the safety of using ketamine in combination with propofol for sedation versus the standard of care analgosedation in patients admitted to the intensive care unit with severe traumatic brain injury. **Detailed Description:** Patients meeting eligibility criteria and consent having been obtained by LAR will undergo randomization to either the ketamine with propofol intervention arm or the standard of care control arm. Patients enrolled in the intervention arm will receive propofol at a rate of 300 mcg/kg/hr (5 mcg/kg/min) with the addition of ketamine at a rate of 1000-5000 mcg/kg/hr (16.67 - 83.33 mcg/kg/min) (using weight at time of admission) with an additional 2 mg/kg (2000 mcg/kg) bolus of ketamine, for sustained ICP elevations over 22mHg for greater than 5 minutes not attributed to other causes (coughing etc.). In the control arm, patients will receive their institutional analgosedation protocol. The sedation protocols will be continued until removal of intracranial pressure monitoring. This study will take place during the participant's hospital care. The clinical team will administer treatment using standard practices, including all safety precautions available. Side effects will be monitored closely and may decide to discontinue the subject's participation in the study should the subject's health or safety are at risk. The research team will performed one outpatient follow-up after study intervention ends. ### Conditions Module **Conditions:** - Severe Traumatic Brain Injury - Intracranial Hypertension - Intracranial Hemorrhage, Hypertensive **Keywords:** - TBI - Severe TBI - Traumatic Brain Injury - Sedation - Ketamine ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 50 **Type:** ESTIMATED **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Propofol at a rate of 300 mcg/kg/hr (5 mcg/kg/min) with the addition of ketamine at a rate of 1000-5000 mcg/kg/hr (16.67 - 83.33 mcg/kg/min) (using weight at time of admission) with an additional 2 mg/kg (2000 mcg/kg) bolus of ketamine **Intervention Names:** - Drug: Ketamine with propofol **Label:** Ketamine with propofol **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Standard of Care analgosedation of choice using propofol, fentanyl, dexmedetomidine, morphine, hydromorphone, midazolam, or lorazepam. **Intervention Names:** - Other: Standard of Care propofol, fentanyl, dexmedetomidine, morphine, hydromorphone, midazolam, or lorazepam **Label:** SOC propofol, fentanyl, dexmedetomidine, morphine, hydromorphone, midazolam, or lorazepam **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Ketamine with propofol **Description:** Propofol at a rate of 300 mcg/kg/hr (5 mcg/kg/min) with the addition of ketamine at a rate of 1000-5000 mcg/kg/hr (16.67 - 83.33 mcg/kg/min) (using weight at time of admission) with an additional 2 mg/kg (2000 mcg/kg) bolus of ketamine **Name:** Ketamine with propofol **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - SOC propofol, fentanyl, dexmedetomidine, morphine, hydromorphone, midazolam, or lorazepam **Description:** Standard of Care analgosedation of choice using propofol, fentanyl, dexmedetomidine, morphine, hydromorphone, midazolam, or lorazepam administered according to the institutional SOC guidelines. **Name:** Standard of Care propofol, fentanyl, dexmedetomidine, morphine, hydromorphone, midazolam, or lorazepam **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** ICP elevations \> 22 mmHg for greater than 5 minutes. **Measure:** Number of ICP elevations greater than 22 mmHg for greater than 5 minutes **Time Frame:** During the maximum 5-day course of study intervention, while patient is sedated and has intracranial pressure monitor in place in the ICU setting **Description:** Mean ICP **Measure:** Mean ICP **Time Frame:** During the maximum 5-day course of study intervention. #### Secondary Outcomes **Description:** Total time spent with ICP \>22 mmHg (in minutes). **Measure:** Total time spent with intracranial pressure (ICP) >22 mmHg **Time Frame:** During the maximum 5-day course of study intervention. **Description:** Mean CPP (in minutes). **Measure:** Mean Cerebral Perfusion Pressure (CPP) **Time Frame:** During the maximum 5-day course of study intervention. **Description:** Total time spent with CPP \<60 mmHg (in minutes). **Measure:** Total time spent with CPP <60 mmHg **Time Frame:** During the maximum 5-day course of study intervention. **Description:** Total number of events where CPP \<60 mmHg (in minutes) for greater than 5 minutes. **Measure:** Total number of events where CPP <60 mmHg for greater than 5 minutes **Time Frame:** During the maximum 5-day course of study intervention. **Description:** Relationship between vasopressor infusion dose and mean arterial blood pressure. VDI= (dobutamine dose × 1) + (dopamine dose × 1) + (norepinephrine dose × 100) + (vasopressin × 100) + (epinephrine × 100))/MAP indicating the relationship of high VDI and poor outcome. **Measure:** Vasopressor dependency index (VDI) **Time Frame:** During the maximum 5-day course of study intervention. **Description:** Incidence of seizures (as documented by EEG). **Measure:** Incidence of seizures **Time Frame:** During the maximum 5-day course of study intervention. **Description:** Incidence of cardiac arrhythmias (other than sinus tachycardia). **Measure:** Incidence of cardiac arrhythmias **Time Frame:** During the maximum 5-day course of study intervention. **Description:** Mean heart rate (HR). **Measure:** Mean heart rate **Time Frame:** During the maximum 5-day course of study intervention. **Description:** Incidence of PTSD at 6-month outpatient follow-up. **Measure:** Incidence of post-traumatic stress disorder (PTSD) in outpatient setting **Time Frame:** Outpatient follow-up six months after intervention. **Description:** GOSE-TBI assessment resulting in subjective measure of 0-8 regarding recovery after injury with higher score indicating greatest recovery to pre-injury life, will be conducted at 6-month outpatient follow-up. **Measure:** Glasgow Coma Outcome Scale extended (GOSE-TBI) scores **Time Frame:** Outpatient follow-up six months after intervention. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Adults 18-65 years of age * Severe traumatic brain injury (TBI), with a Glasgow Coma Scale (GCS) ≤ 8, requiring intracranial monitoring * Placement of intracranial pressure monitor * Receiving treatment in an intensive care unit (ICU) Exclusion Criteria: * Significant cardiovascular disease with recent coronary intervention * Pregnancy * Prisoners * Known allergy to ketamine or propofol **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Marisa F Rodriguez **Phone:** 210-851-5779 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Martin R Cota, MPH **Phone:** 301-295-9685 **Role:** CONTACT ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Iaccarino C, Carretta A, Nicolosi F, Morselli C. Epidemiology of severe traumatic brain injury. J Neurosurg Sci. 2018 Oct;62(5):535-541. doi: 10.23736/S0390-5616.18.04532-0. **PMID:** 30182649 **Citation:** Agrawal D, Raghavendran K, Schaubel DE, Mishra MC, Rajajee V. A Propensity Score Analysis of the Impact of Invasive Intracranial Pressure Monitoring on Outcomes after Severe Traumatic Brain Injury. J Neurotrauma. 2016 May 1;33(9):853-8. doi: 10.1089/neu.2015.4015. Epub 2015 Oct 8. **PMID:** 26414629 **Citation:** Butcher I, Maas AI, Lu J, Marmarou A, Murray GD, Mushkudiani NA, McHugh GS, Steyerberg EW. Prognostic value of admission blood pressure in traumatic brain injury: results from the IMPACT study. J Neurotrauma. 2007 Feb;24(2):294-302. doi: 10.1089/neu.2006.0032. **PMID:** 17375994 **Citation:** McHugh GS, Engel DC, Butcher I, Steyerberg EW, Lu J, Mushkudiani N, Hernandez AV, Marmarou A, Maas AI, Murray GD. Prognostic value of secondary insults in traumatic brain injury: results from the IMPACT study. J Neurotrauma. 2007 Feb;24(2):287-93. doi: 10.1089/neu.2006.0031. **PMID:** 17375993 **Citation:** Murray GD, Butcher I, McHugh GS, Lu J, Mushkudiani NA, Maas AI, Marmarou A, Steyerberg EW. Multivariable prognostic analysis in traumatic brain injury: results from the IMPACT study. J Neurotrauma. 2007 Feb;24(2):329-37. doi: 10.1089/neu.2006.0035. **PMID:** 17375997 **Citation:** Petkus V, Preiksaitis A, Chaleckas E, Chomskis R, Zubaviciute E, Vosylius S, Rocka S, Rastenyte D, Aries MJ, Ragauskas A, Neumann JO. Optimal Cerebral Perfusion Pressure: Targeted Treatment for Severe Traumatic Brain Injury. J Neurotrauma. 2020 Jan 15;37(2):389-396. doi: 10.1089/neu.2019.6551. Epub 2019 Nov 13. **PMID:** 31583962 **Citation:** Carney N, Totten AM, O'Reilly C, Ullman JS, Hawryluk GW, Bell MJ, Bratton SL, Chesnut R, Harris OA, Kissoon N, Rubiano AM, Shutter L, Tasker RC, Vavilala MS, Wilberger J, Wright DW, Ghajar J. Guidelines for the Management of Severe Traumatic Brain Injury, Fourth Edition. Neurosurgery. 2017 Jan 1;80(1):6-15. doi: 10.1227/NEU.0000000000001432. **PMID:** 27654000 **Citation:** Cooper DJ, Rosenfeld JV, Murray L, Arabi YM, Davies AR, D'Urso P, Kossmann T, Ponsford J, Seppelt I, Reilly P, Wolfe R; DECRA Trial Investigators; Australian and New Zealand Intensive Care Society Clinical Trials Group. Decompressive craniectomy in diffuse traumatic brain injury. N Engl J Med. 2011 Apr 21;364(16):1493-502. doi: 10.1056/NEJMoa1102077. Epub 2011 Mar 25. Erratum In: N Engl J Med. 2011 Nov 24;365(21):2040. **PMID:** 21434843 **Citation:** Hawryluk GWJ, Aguilera S, Buki A, Bulger E, Citerio G, Cooper DJ, Arrastia RD, Diringer M, Figaji A, Gao G, Geocadin R, Ghajar J, Harris O, Hoffer A, Hutchinson P, Joseph M, Kitagawa R, Manley G, Mayer S, Menon DK, Meyfroidt G, Michael DB, Oddo M, Okonkwo D, Patel M, Robertson C, Rosenfeld JV, Rubiano AM, Sahuquillo J, Servadei F, Shutter L, Stein D, Stocchetti N, Taccone FS, Timmons S, Tsai E, Ullman JS, Vespa P, Videtta W, Wright DW, Zammit C, Chesnut RM. A management algorithm for patients with intracranial pressure monitoring: the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC). Intensive Care Med. 2019 Dec;45(12):1783-1794. doi: 10.1007/s00134-019-05805-9. Epub 2019 Oct 28. **PMID:** 31659383 **Citation:** Hutchinson PJ, Kolias AG, Timofeev IS, Corteen EA, Czosnyka M, Timothy J, Anderson I, Bulters DO, Belli A, Eynon CA, Wadley J, Mendelow AD, Mitchell PM, Wilson MH, Critchley G, Sahuquillo J, Unterberg A, Servadei F, Teasdale GM, Pickard JD, Menon DK, Murray GD, Kirkpatrick PJ; RESCUEicp Trial Collaborators. Trial of Decompressive Craniectomy for Traumatic Intracranial Hypertension. N Engl J Med. 2016 Sep 22;375(12):1119-30. doi: 10.1056/NEJMoa1605215. Epub 2016 Sep 7. **PMID:** 27602507 **Citation:** Oddo M, Crippa IA, Mehta S, Menon D, Payen JF, Taccone FS, Citerio G. Optimizing sedation in patients with acute brain injury. Crit Care. 2016 May 5;20(1):128. doi: 10.1186/s13054-016-1294-5. **PMID:** 27145814 **Citation:** Stein DM, Hu PF, Brenner M, Sheth KN, Liu KH, Xiong W, Aarabi B, Scalea TM. Brief episodes of intracranial hypertension and cerebral hypoperfusion are associated with poor functional outcome after severe traumatic brain injury. J Trauma. 2011 Aug;71(2):364-73; discussion 373-4. doi: 10.1097/TA.0b013e31822820da. **PMID:** 21825940 **Citation:** Gardner AE, Dannemiller FJ, Dean D. Intracranial cerebrospinal fluid pressure in man during ketamine anesthesia. Anesth Analg. 1972 Sep-Oct;51(5):741-5. No abstract available. **PMID:** 4672167 **Citation:** Gibbs JM. The effect of intravenous ketamine on cerebrospinal fluid pressure. Br J Anaesth. 1972 Dec;44(12):1298-302. doi: 10.1093/bja/44.12.1298. No abstract available. **PMID:** 4650346 **Citation:** Green SM, Andolfatto G, Krauss BS. Ketamine and intracranial pressure: no contraindication except hydrocephalus. Ann Emerg Med. 2015 Jan;65(1):52-4. doi: 10.1016/j.annemergmed.2014.08.025. Epub 2014 Sep 20. No abstract available. **PMID:** 25245275 **Citation:** Gregers MCT, Mikkelsen S, Lindvig KP, Brochner AC. Ketamine as an Anesthetic for Patients with Acute Brain Injury: A Systematic Review. Neurocrit Care. 2020 Aug;33(1):273-282. doi: 10.1007/s12028-020-00975-7. **PMID:** 32328972 **Citation:** Laws JC, Vance EH, Betters KA, Anderson JJ, Fleishman S, Bonfield CM, Wellons JC 3rd, Xu M, Slaughter JC, Giuse DA, Patel N, Jordan LC, Wolf MS. Acute Effects of Ketamine on Intracranial Pressure in Children With Severe Traumatic Brain Injury. Crit Care Med. 2023 May 1;51(5):563-572. doi: 10.1097/CCM.0000000000005806. Epub 2023 Feb 21. **PMID:** 36825892 **Citation:** Dengler BA, Karam O, Barthol CA, Chance A, Snider LE, Mundy CM, Bounajem MT, Johnson WC, Maita MM, Mendez-Gomez PM, Seifi A, Hafeez S. Ketamine Boluses Are Associated with a Reduction in Intracranial Pressure and an Increase in Cerebral Perfusion Pressure: A Retrospective Observational Study of Patients with Severe Traumatic Brain Injury. Crit Care Res Pract. 2022 May 21;2022:3834165. doi: 10.1155/2022/3834165. eCollection 2022. **PMID:** 35637760 **Citation:** Bebarta VS, Mora AG, Bebarta EK, Reeves LK, Maddry JK, Schauer SG, Lairet JR. Prehospital Use of Ketamine in the Combat Setting: A Sub-Analysis of Patients With Head Injuries Evaluated in the Prospective Life Saving Intervention Study. Mil Med. 2020 Jan 7;185(Suppl 1):136-142. doi: 10.1093/milmed/usz302. **PMID:** 32074369 **Citation:** Hill GJ, April MD, Maddry JK, Schauer SG. Prehospital ketamine administration to pediatric trauma patients with head injuries in combat theaters. Am J Emerg Med. 2019 Aug;37(8):1455-1459. doi: 10.1016/j.ajem.2018.10.046. Epub 2018 Oct 22. **PMID:** 30528051 **Citation:** Maheswari N, Panda NB, Mahajan S, Luthra A, Pattnaik S, Bhatia N, Karthigeyan M, Kaloria N, Chauhan R, Soni S, Jangra K, Bhagat H. Ketofol as an Anesthetic Agent in Patients With Isolated Moderate to Severe Traumatic Brain Injury: A Prospective, Randomized Double-blind Controlled Trial. J Neurosurg Anesthesiol. 2023 Jan 1;35(1):49-55. doi: 10.1097/ANA.0000000000000774. Epub 2021 May 13. **PMID:** 36745167 **Citation:** Dewan MC, Rattani A, Gupta S, Baticulon RE, Hung YC, Punchak M, Agrawal A, Adeleye AO, Shrime MG, Rubiano AM, Rosenfeld JV, Park KB. Estimating the global incidence of traumatic brain injury. J Neurosurg. 2018 Apr 27;130(4):1080-1097. doi: 10.3171/2017.10.JNS17352. **PMID:** 29701556 **Citation:** Stein SC, Georgoff P, Meghan S, Mizra K, Sonnad SS. 150 years of treating severe traumatic brain injury: a systematic review of progress in mortality. J Neurotrauma. 2010 Jul;27(7):1343-53. doi: 10.1089/neu.2009.1206. **PMID:** 20392140 **Citation:** Mangat HS, Wu X, Gerber LM, Shabani HK, Lazaro A, Leidinger A, Santos MM, McClelland PH, Schenck H, Joackim P, Ngerageza JG, Schmidt F, Stieg PE, Hartl R. Severe traumatic brain injury management in Tanzania: analysis of a prospective cohort. J Neurosurg. 2021 Jan 22;135(4):1190-1202. doi: 10.3171/2020.8.JNS201243. **PMID:** 33482641 **Citation:** Howard JT, Stewart IJ, Amuan M, Janak JC, Pugh MJ. Association of Traumatic Brain Injury With Mortality Among Military Veterans Serving After September 11, 2001. JAMA Netw Open. 2022 Feb 1;5(2):e2148150. doi: 10.1001/jamanetworkopen.2021.48150. **PMID:** 35147684 **Citation:** Rutherford GW, Wlodarczyk RC. Distant sequelae of traumatic brain injury: premature mortality and intracranial neoplasms. J Head Trauma Rehabil. 2009 Nov-Dec;24(6):468-74. doi: 10.1097/HTR.0b013e3181c133d2. **PMID:** 19940680 **Citation:** Kang HK, Bullman TA. Mortality among U.S. veterans of the Persian Gulf War. N Engl J Med. 1996 Nov 14;335(20):1498-504. doi: 10.1056/NEJM199611143352006. **PMID:** 8890102 **Citation:** Bollinger MJ, Schmidt S, Pugh JA, Parsons HM, Copeland LA, Pugh MJ. Erosion of the healthy soldier effect in veterans of US military service in Iraq and Afghanistan. Popul Health Metr. 2015 Mar 18;13:8. doi: 10.1186/s12963-015-0040-6. eCollection 2015. **PMID:** 25798075 **Citation:** Dismuke CE, Walker RJ, Egede LE. Utilization and Cost of Health Services in Individuals With Traumatic Brain Injury. Glob J Health Sci. 2015 Apr 19;7(6):156-69. doi: 10.5539/gjhs.v7n6p156. **PMID:** 26153156 **Citation:** Bullock MR, Chesnut R, Ghajar J, Gordon D, Hartl R, Newell DW, Servadei F, Walters BC, Wilberger JE; Surgical Management of Traumatic Brain Injury Author Group. Surgical management of acute epidural hematomas. Neurosurgery. 2006 Mar;58(3 Suppl):S7-15; discussion Si-iv. **PMID:** 16710967 **Citation:** Bullock MR, Chesnut R, Ghajar J, Gordon D, Hartl R, Newell DW, Servadei F, Walters BC, Wilberger JE; Surgical Management of Traumatic Brain Injury Author Group. Surgical management of acute subdural hematomas. Neurosurgery. 2006 Mar;58(3 Suppl):S16-24; discussion Si-iv. **PMID:** 16710968 **Citation:** Bullock MR, Chesnut R, Ghajar J, Gordon D, Hartl R, Newell DW, Servadei F, Walters BC, Wilberger J; Surgical Management of Traumatic Brain Injury Author Group. Surgical management of traumatic parenchymal lesions. Neurosurgery. 2006 Mar;58(3 Suppl):S25-46; discussion Si-iv. doi: 10.1227/01.NEU.0000210365.36914.E3. **PMID:** 16540746 **Citation:** Donnelly J, Czosnyka M, Adams H, Cardim D, Kolias AG, Zeiler FA, Lavinio A, Aries M, Robba C, Smielewski P, Hutchinson PJA, Menon DK, Pickard JD, Budohoski KP. Twenty-Five Years of Intracranial Pressure Monitoring After Severe Traumatic Brain Injury: A Retrospective, Single-Center Analysis. Neurosurgery. 2019 Jul 1;85(1):E75-E82. doi: 10.1093/neuros/nyy468. **PMID:** 30476233 **Citation:** Farahvar A, Gerber LM, Chiu YL, Carney N, Hartl R, Ghajar J. Increased mortality in patients with severe traumatic brain injury treated without intracranial pressure monitoring. J Neurosurg. 2012 Oct;117(4):729-34. doi: 10.3171/2012.7.JNS111816. Epub 2012 Aug 17. **PMID:** 22900846 **Citation:** Badri S, Chen J, Barber J, Temkin NR, Dikmen SS, Chesnut RM, Deem S, Yanez ND, Treggiari MM. Mortality and long-term functional outcome associated with intracranial pressure after traumatic brain injury. Intensive Care Med. 2012 Nov;38(11):1800-9. doi: 10.1007/s00134-012-2655-4. Epub 2012 Aug 3. **PMID:** 23011528 **Citation:** Marshall LF, Smith RW, Shapiro HM. The outcome with aggressive treatment in severe head injuries. Part I: the significance of intracranial pressure monitoring. J Neurosurg. 1979 Jan;50(1):20-5. doi: 10.3171/jns.1979.50.1.0020. No abstract available. **PMID:** 758374 **Citation:** Lowell HM, Bloor BM. The effect of increased intracranial pressure on cerebrovascular hemodynamics. J Neurosurg. 1971 Jun;34(6):760-9. doi: 10.3171/jns.1971.34.6.0760. No abstract available. **PMID:** 4997951 **Citation:** Akerlund CA, Donnelly J, Zeiler FA, Helbok R, Holst A, Cabeleira M, Guiza F, Meyfroidt G, Czosnyka M, Smielewski P, Stocchetti N, Ercole A, Nelson DW; CENTER-TBI High Resolution ICU Sub-Study Participants and Investigators. Impact of duration and magnitude of raised intracranial pressure on outcome after severe traumatic brain injury: A CENTER-TBI high-resolution group study. PLoS One. 2020 Dec 14;15(12):e0243427. doi: 10.1371/journal.pone.0243427. eCollection 2020. **PMID:** 33315872 **Citation:** Sheth KN, Stein DM, Aarabi B, Hu P, Kufera JA, Scalea TM, Hanley DF. Intracranial pressure dose and outcome in traumatic brain injury. Neurocrit Care. 2013 Feb;18(1):26-32. doi: 10.1007/s12028-012-9780-3. **PMID:** 23055087 **Citation:** Wolf S, Mielke D, Barner C, Malinova V, Kerz T, Wostrack M, Czorlich P, Salih F, Engel DC, Ehlert A, Staykov D, Alturki AY, Sure U, Bardutzky J, Schroeder HWS, Schurer L, Beck J, Juratli TA, Fritsch M, Lemcke J, Pohrt A, Meyer B, Schwab S, Rohde V, Vajkoczy P; EARLYDRAIN Study Group. Effectiveness of Lumbar Cerebrospinal Fluid Drain Among Patients With Aneurysmal Subarachnoid Hemorrhage: A Randomized Clinical Trial. JAMA Neurol. 2023 Aug 1;80(8):833-842. doi: 10.1001/jamaneurol.2023.1792. Erratum In: JAMA Neurol. 2023 Aug 1;80(8):873. **PMID:** 37330974 **Citation:** Cooper DJ, Nichol AD, Bailey M, Bernard S, Cameron PA, Pili-Floury S, Forbes A, Gantner D, Higgins AM, Huet O, Kasza J, Murray L, Newby L, Presneill JJ, Rashford S, Rosenfeld JV, Stephenson M, Vallance S, Varma D, Webb SAR, Trapani T, McArthur C; POLAR Trial Investigators and the ANZICS Clinical Trials Group. Effect of Early Sustained Prophylactic Hypothermia on Neurologic Outcomes Among Patients With Severe Traumatic Brain Injury: The POLAR Randomized Clinical Trial. JAMA. 2018 Dec 4;320(21):2211-2220. doi: 10.1001/jama.2018.17075. **PMID:** 30357266 **Citation:** Roquilly A, Moyer JD, Huet O, Lasocki S, Cohen B, Dahyot-Fizelier C, Chalard K, Seguin P, Jeantrelle C, Vermeersch V, Gaillard T, Cinotti R, Demeure Dit Latte D, Mahe PJ, Vourc'h M, Martin FP, Chopin A, Lerebourg C, Flet L, Chiffoleau A, Feuillet F, Asehnoune K; Atlanrea Study Group and the Societe Francaise d'Anesthesie Reanimation (SFAR) Research Network. Effect of Continuous Infusion of Hypertonic Saline vs Standard Care on 6-Month Neurological Outcomes in Patients With Traumatic Brain Injury: The COBI Randomized Clinical Trial. JAMA. 2021 May 25;325(20):2056-2066. doi: 10.1001/jama.2021.5561. **PMID:** 34032829 **Citation:** Skolnick BE, Maas AI, Narayan RK, van der Hoop RG, MacAllister T, Ward JD, Nelson NR, Stocchetti N; SYNAPSE Trial Investigators. A clinical trial of progesterone for severe traumatic brain injury. N Engl J Med. 2014 Dec 25;371(26):2467-76. doi: 10.1056/NEJMoa1411090. Epub 2014 Dec 10. **PMID:** 25493978 **Citation:** CRASH-3 trial collaborators. Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial. Lancet. 2019 Nov 9;394(10210):1713-1723. doi: 10.1016/S0140-6736(19)32233-0. Epub 2019 Oct 14. Erratum In: Lancet. 2019 Nov 9;394(10210):1712. **PMID:** 31623894 **Citation:** Bourgoin A, Albanese J, Wereszczynski N, Charbit M, Vialet R, Martin C. Safety of sedation with ketamine in severe head injury patients: comparison with sufentanil. Crit Care Med. 2003 Mar;31(3):711-7. doi: 10.1097/01.CCM.0000044505.24727.16. **PMID:** 12626974 **Citation:** Bourgoin A, Leone M, Delmas A, Garnier F, Albanese J, Martin C. Increasing mean arterial pressure in patients with septic shock: effects on oxygen variables and renal function. Crit Care Med. 2005 Apr;33(4):780-6. doi: 10.1097/01.ccm.0000157788.20591.23. **PMID:** 15818105 **Citation:** Kolenda H, Gremmelt A, Rading S, Braun U, Markakis E. Ketamine for analgosedative therapy in intensive care treatment of head-injured patients. Acta Neurochir (Wien). 1996;138(10):1193-9. doi: 10.1007/BF01809750. Erratum In: Acta Neurochir (Wien) 1997;139(12):1193. **PMID:** 8955439 **Citation:** Schmittner MD, Vajkoczy SL, Horn P, Bertsch T, Quintel M, Vajkoczy P, Muench E. Effects of fentanyl and S(+)-ketamine on cerebral hemodynamics, gastrointestinal motility, and need of vasopressors in patients with intracranial pathologies: a pilot study. J Neurosurg Anesthesiol. 2007 Oct;19(4):257-62. doi: 10.1097/ANA.0b013e31811f3feb. **PMID:** 17893578 **Citation:** Sakpal TV. Sample size estimation in clinical trial. Perspect Clin Res. 2010 Apr;1(2):67-9. **PMID:** 21829786 **Citation:** Military Health System and Defense Health Agency. DOD TBI Worldwide Numbers: Traumatic Brain Injury Center of Excellence; 2022 [Available from: https://health.mil/Military-Health-Topics/Centers-of-Excellence/Traumatic-Brain-Injury-Center-of-Excellence/DOD-TBI-Worldwide-NumbersTraumaticBrain]. **Citation:** Michalczyk, Lukasz, and Lukasz Kaczmarek. **Citation:** Chan, Kai En, et al. ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000006259 - Term: Craniocerebral Trauma - ID: D000020196 - Term: Trauma, Nervous System - ID: D000010335 - Term: Pathologic Processes - ID: D000002561 - Term: Cerebrovascular Disorders ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M10024 - Name: Hypertension - Relevance: LOW - As Found: Unknown - ID: M5207 - Name: Brain Injuries - Relevance: HIGH - As Found: Brain Injury - ID: M628 - Name: Brain Injuries, Traumatic - Relevance: HIGH - As Found: Traumatic Brain Injury - ID: M9556 - Name: Hemorrhage - Relevance: HIGH - As Found: Hemorrhage - ID: M21521 - Name: Intracranial Hypertension - Relevance: HIGH - As Found: Intracranial Hypertension - ID: M22113 - Name: Intracranial Hemorrhages - Relevance: HIGH - As Found: Intracranial Hemorrhage - ID: M22112 - Name: Intracranial Hemorrhage, Hypertensive - Relevance: HIGH - As Found: Intracranial Hemorrhage, Hypertensive - ID: M17685 - Name: Wounds and Injuries - Relevance: HIGH - As Found: Injury - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: M5204 - Name: Brain Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M9349 - Name: Craniocerebral Trauma - Relevance: LOW - As Found: Unknown - ID: M22023 - Name: Trauma, Nervous System - Relevance: LOW - As Found: Unknown - ID: M5810 - Name: Cerebrovascular Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001930 - Term: Brain Injuries - ID: D000070642 - Term: Brain Injuries, Traumatic - ID: D000020300 - Term: Intracranial Hemorrhages - ID: D000019586 - Term: Intracranial Hypertension - ID: D000020299 - Term: Intracranial Hemorrhage, Hypertensive - ID: D000006470 - Term: Hemorrhage - ID: D000014947 - Term: Wounds and Injuries ### Intervention Browse Module - Ancestors - ID: D000006993 - Term: Hypnotics and Sedatives - ID: D000002492 - Term: Central Nervous System Depressants - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000018712 - Term: Analgesics, Non-Narcotic - ID: D000000700 - Term: Analgesics - ID: D000018689 - Term: Sensory System Agents - ID: D000018373 - Term: Peripheral Nervous System Agents - ID: D000058647 - Term: Adrenergic alpha-2 Receptor Agonists - ID: D000000316 - Term: Adrenergic alpha-Agonists - ID: D000000322 - Term: Adrenergic Agonists - ID: D000018663 - Term: Adrenergic Agents - ID: D000018377 - Term: Neurotransmitter Agents - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000018686 - Term: Anesthetics, Intravenous - ID: D000018681 - Term: Anesthetics, General - ID: D000000777 - Term: Anesthetics - ID: D000000778 - Term: Anesthetics, Dissociative - ID: D000018691 - Term: Excitatory Amino Acid Antagonists - ID: D000018683 - Term: Excitatory Amino Acid Agents - ID: D000000701 - Term: Analgesics, Opioid - ID: D000009294 - Term: Narcotics - ID: D000000759 - Term: Adjuvants, Anesthesia - ID: D000014151 - Term: Anti-Anxiety Agents - ID: D000014149 - Term: Tranquilizing Agents - ID: D000011619 - Term: Psychotropic Drugs - ID: D000018757 - Term: GABA Modulators - ID: D000018682 - Term: GABA Agents - ID: D000000927 - Term: Anticonvulsants - ID: D000000932 - Term: Antiemetics - ID: D000001337 - Term: Autonomic Agents - ID: D000005765 - Term: Gastrointestinal Agents ### Intervention Browse Module - Browse Branches - Abbrev: Analg - Name: Analgesics - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: AdjAn - Name: Adjuvants, Anesthesia - Abbrev: PsychDr - Name: Psychotropic Drugs - Abbrev: AntiConv - Name: Anticonvulsants - Abbrev: AnEm - Name: Antiemetics - Abbrev: Gast - Name: Gastrointestinal Agents ### Intervention Browse Module - Browse Leaves - ID: M11982 - Name: Morphine - Relevance: HIGH - As Found: Screening - ID: M8418 - Name: Fentanyl - Relevance: HIGH - As Found: Induction - ID: M22662 - Name: Dexmedetomidine - Relevance: HIGH - As Found: Placebo-controlled - ID: M11845 - Name: Midazolam - Relevance: HIGH - As Found: Scan - ID: M10674 - Name: Ketamine - Relevance: HIGH - As Found: Any - ID: M7275 - Name: Hydromorphone - Relevance: HIGH - As Found: Endurance - ID: M11140 - Name: Lorazepam - Relevance: HIGH - As Found: Circulation - ID: M18307 - Name: Propofol - Relevance: HIGH - As Found: COVID-19 - ID: M10043 - Name: Hypnotics and Sedatives - Relevance: LOW - As Found: Unknown - ID: M4032 - Name: Analgesics - Relevance: LOW - As Found: Unknown - ID: M20786 - Name: Analgesics, Non-Narcotic - Relevance: LOW - As Found: Unknown - ID: M20746 - Name: Adrenergic Agents - Relevance: LOW - As Found: Unknown - ID: M3668 - Name: Adrenergic alpha-Agonists - Relevance: LOW - As Found: Unknown - ID: M3673 - Name: Adrenergic Agonists - Relevance: LOW - As Found: Unknown - ID: M20504 - Name: Neurotransmitter Agents - Relevance: LOW - As Found: Unknown - ID: M4107 - Name: Anesthetics - Relevance: LOW - As Found: Unknown - ID: M20766 - Name: Anesthetics, Intravenous - Relevance: LOW - As Found: Unknown - ID: M20761 - Name: Anesthetics, General - Relevance: LOW - As Found: Unknown - ID: M4108 - Name: Anesthetics, Dissociative - Relevance: LOW - As Found: Unknown - ID: M20771 - Name: Excitatory Amino Acid Antagonists - Relevance: LOW - As Found: Unknown - ID: M4033 - Name: Analgesics, Opioid - Relevance: LOW - As Found: Unknown - ID: M12245 - Name: Narcotics - Relevance: LOW - As Found: Unknown - ID: M4089 - Name: Adjuvants, Anesthesia - Relevance: LOW - As Found: Unknown - ID: M16905 - Name: Anti-Anxiety Agents - Relevance: LOW - As Found: Unknown - ID: M14474 - Name: Psychotropic Drugs - Relevance: LOW - As Found: Unknown - ID: M20827 - Name: GABA Modulators - Relevance: LOW - As Found: Unknown - ID: M4246 - Name: Anticonvulsants - Relevance: LOW - As Found: Unknown - ID: M4251 - Name: Antiemetics - Relevance: LOW - As Found: Unknown - ID: M8881 - Name: Gastrointestinal Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000008874 - Term: Midazolam - ID: D000005283 - Term: Fentanyl - ID: D000020927 - Term: Dexmedetomidine - ID: D000007649 - Term: Ketamine - ID: D000009020 - Term: Morphine - ID: D000004091 - Term: Hydromorphone - ID: D000008140 - Term: Lorazepam - ID: D000015742 - Term: Propofol ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429644 **Brief Title:** Long-term Oncologic Outcome of Breast-conserving Surgery in Breast Cancer Patients With BRCA1/2 Mutations **Official Title:** Ong-term Oncologic Outcome of Breast-conserving Surgery in Breast Cancer Patients With BRCA1/2 Mutations #### Organization Study ID Info **ID:** 2022-04-039 #### Organization **Class:** OTHER **Full Name:** Hanyang University Seoul Hospital ### Status Module #### Completion Date **Date:** 2024-04-08 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-23 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2023-12-31 **Type:** ACTUAL #### Start Date **Date:** 2022-07-07 **Type:** ACTUAL **Status Verified Date:** 2024-04 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-04-30 **Study First Submit QC Date:** 2024-05-23 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** Korean Surgical Society **Class:** UNKNOWN **Name:** Korea Robot-Endoscopy Minimal Access Breast Surgery Study Group #### Lead Sponsor **Class:** OTHER **Name:** Hanyang University Seoul Hospital #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The investigators matched BCS and mastectomy group using propensity scores and analyzed the recurrence and survival among the evenly matched patients in breast cancer patients with BRCA 1/2 mutations. **Detailed Description:** The purpose of study is to assess the oncologic safety of BCS in patients carrying BRCA1/2 mutations by comparing long-term outcomes with mastectomy. The investigators matched BCS and mastectomy group using propensity scores and analyzed the recurrence and survival among the evenly matched patients. By providing insights into the feasibility of BCS for patients with BRCA1/2 mutations, the investigators aim to present evidence to aid in surgical decision-making for the care of these patients. ### Conditions Module **Conditions:** - BRCA1/2 Mutation - Breast-conserving Surgery ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** RETROSPECTIVE #### Enrollment Info **Count:** 4010 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Department of Surgery, Dongtan Sacred Heart Hospital, Hallym University, Dongtan, Republic of Korea **Intervention Names:** - Procedure: Breast-conserving surgery **Label:** Dongtan Sacred Heart Hospital #### Arm Group 2 **Description:** Division of Breast Surgery, Department of Surgery, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Republic of Korea **Intervention Names:** - Procedure: Breast-conserving surgery **Label:** Samsung Medical Center #### Arm Group 3 **Description:** Breast Care Center, Department of Surgery, Seoul National University Hospital, Seoul, Republic of Korea **Intervention Names:** - Procedure: Breast-conserving surgery **Label:** Seoul National University Hospital #### Arm Group 4 **Description:** Department of Surgery, Severance hospital, Yonsei University College of Medicine, Seoul, Republic of Korea **Intervention Names:** - Procedure: Breast-conserving surgery **Label:** Severance hospital #### Arm Group 5 **Description:** Department of Surgery, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu, Republic of Korea **Intervention Names:** - Procedure: Breast-conserving surgery **Label:** Kyungpook National University Chilgok Hospital #### Arm Group 6 **Description:** Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea **Intervention Names:** - Procedure: Breast-conserving surgery **Label:** Gangnam Severance Hospital #### Arm Group 7 **Description:** Department of Surgery, Hanyang University Medical Center, Hanyang University College of Medicine, Seoul, Republic of Korea **Intervention Names:** - Procedure: Breast-conserving surgery **Label:** Hanyang University Medical Center #### Arm Group 8 **Description:** Department of Breast \& Endocrine Surgery, Hallym University Sacred Heart Hospital, Hallym University, Anyang, Republic of Korea **Intervention Names:** - Procedure: Breast-conserving surgery **Label:** Hallym University Sacred Heart Hospital #### Arm Group 9 **Description:** Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea **Intervention Names:** - Procedure: Breast-conserving surgery **Label:** Kangbuk Samsung Hospital #### Arm Group 10 **Description:** Department of Surgery, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Republic of Korea **Intervention Names:** - Procedure: Breast-conserving surgery **Label:** Incheon St. Mary's Hospital #### Arm Group 11 **Description:** Department of Surgery, Kyung Hee University Hospital, Seoul, Republic of Korea **Intervention Names:** - Procedure: Breast-conserving surgery **Label:** Kyung Hee University Hospital #### Arm Group 12 **Description:** Department of Surgery, Keimyung University School of Medicine, Daegu, Republic of Korea **Intervention Names:** - Procedure: Breast-conserving surgery **Label:** Keimyung University School of Medicine #### Arm Group 13 **Description:** Division of Breast Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea **Intervention Names:** - Procedure: Breast-conserving surgery **Label:** Asan Medical Center ### Interventions #### Intervention 1 **Arm Group Labels:** - Asan Medical Center - Dongtan Sacred Heart Hospital - Gangnam Severance Hospital - Hallym University Sacred Heart Hospital - Hanyang University Medical Center - Incheon St. Mary's Hospital - Kangbuk Samsung Hospital - Keimyung University School of Medicine - Kyung Hee University Hospital - Kyungpook National University Chilgok Hospital - Samsung Medical Center - Seoul National University Hospital - Severance hospital **Description:** Breast-conserving surgery, also known as breast-conserving therapy or lumpectomy, is a surgical procedure used to treat breast cancer while preserving as much of the breast tissue as possible. During this procedure, the surgeon removes the cancerous tumor along with a surrounding margin of normal tissue. The goal is to remove the cancerous cells while maintaining the appearance and function of the breast as much as possible. **Name:** Breast-conserving surgery **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** Recurrence in breast or chest wall and/or regional lymph nodes **Measure:** Locoregional recurrence-free survival **Time Frame:** Duration from diagnosis until the development of recurrence up to 10year **Description:** Recurrence in a distant organ **Measure:** Distant recurrence-free survival **Time Frame:** Duration from diagnosis until the development of recurrence up to 10year **Description:** Any form of disease recurrence **Measure:** Recurrence-free survival **Time Frame:** Duration from diagnosis until the development of recurrence up to 10year ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Primary invasive breast cancer who underwent BCS or mastectomy * Received a BRCA1/2 mutation test Exclusion Criteria: * Patients with de novo metastasis * Pregnancy-associated breast cancer **Maximum Age:** 80 Years **Minimum Age:** 20 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** The ON-BRCAII is multi-institution cohort study being conducted by the Korea Robot-Endoscopy Minimal Access Breast Surgery Study Group (KoREa-BSG). Patients with primary breast cancer who underwent BCS or mastectomy and received a BRCA1/2 mutation test between January 2008 and December 2015 were retrospectively identified from 13 institutions in South Korea. The inclusion criteria comprised patients aged 20 to 80 years with invasive breast cancer (pT1-3, N0-3). The exclusion criteria consisted of patients with de novo metastasis and those with pregnancy-associated breast cancer. ### Contacts Locations Module #### Locations **Location 1:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Hanyang university hospital ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M5220 - Name: Breast Neoplasms - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429631 **Brief Title:** The Effect of CIC Education on QOL and Compliance With Mobile Application in Individuals With Spinal Cord Injury. **Official Title:** The Effect of CIC Education on Quality of Life and Compliance With Mobile Application After Discharge in Individuals With Spinal Cord Injury (CIC: Clean Intermittent Catheterization) #### Organization Study ID Info **ID:** 77082166-302.08.01-424987 #### Organization **Class:** OTHER **Full Name:** Gaziler Physical Medicine and Rehabilitation Education and Research Hospital ### Status Module #### Completion Date **Date:** 2024-08-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-23 **Overall Status:** ENROLLING_BY_INVITATION #### Primary Completion Date **Date:** 2024-08-31 **Type:** ESTIMATED #### Start Date **Date:** 2023-09-15 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-18 **Study First Submit QC Date:** 2024-05-23 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Gazi University #### Lead Sponsor **Class:** OTHER **Name:** Gaziler Physical Medicine and Rehabilitation Education and Research Hospital #### Responsible Party **Investigator Affiliation:** Gaziler Physical Medicine and Rehabilitation Education and Research Hospital **Investigator Full Name:** Nilgün Aras **Investigator Title:** Nurse, MSN **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Neurogenic bladder is a condition that occurs due to nerve damage or congenital problems and causes urination disorders. Nowadays, in individuals diagnosed with neurogenic bladder, Clean Intermittent Catheterization is often used to evacuate the urine accumulated in the bladder. Clean Intermittent Catheterization(CIC) is a simple, safe and effective method in which the catheter is placed through the meatus. In this application, the catheter is removed without waiting after urine drainage is achieved. This process is usually performed on its own. Since IC(Intermittent Catheterization) is a procedure performed on the bladder, it may cause some complications. IC application must be performed successfully to prevent or reduce complications. The success of the technique largely depends on patient education and follow-up. Sometimes patients may not be able to come to the hospital for follow-up and feedback after IC training. Innovations are needed to ensure the continuation of distance education so that the education of patients who cannot come to the hospital is not incomplete. The literature includes brochures, videos, websites and some mobile applications for IC training. However, no application has been found that monitors patients' urine amounts. This research was planned to examine the effect of clean intermittent catheterization training given via mobile application to individuals with spinal cord injury on their quality of life and compliance. **Detailed Description:** scales: 1. Information form: Authors will ask to patients age, weight, height, gender, marital status, education level, diagnosis, time of injury, cause of injury, independence level, working or not working, presence of spasticity, presence of complications 2. WHOQOL-BREF(World Health Organization Quality of Life Scale):The WHO Quality of Life Assessment (WHOQOL) is a generic quality of life instrument that was designed to be applicable to people living under different circumstances, conditions, and cultures. The short version known as WHOQOL-BREF with 26 items. It is based on a Likert-type scale and is scored from 1 to 5, with higher scores indicating a better quality of life. 3. Intermittent Self-Catheterization Questionnaire (ISC-Q): This is a 24-item self-administered questionnaire. Each item is scored on a 5-point Likert-type scale ranging from 0 (strongly disagree) to 4 (strongly agree), and after the conversion of the 14 reverse-coded items to give a common range of 0-100, the scores are calculated by multiplying the mean value of all items within each domain by 25. The total ISC-Q score is then calculated from the simple average from across the four domains (0-100), with higher scores indicating a higher quality of life. 4. Intermittent Catheterization Adherence Scale (ICAS): ICAS (IntermittentCatheterization Adherence Scale) is used to assess long-term patient adherence to prescribed ISC treatment. Binary answers were used for the first seven questions:yes = 1, no = 0, whereas the response options for the eighth question were graded on a 5-point Likert-type scale: 0 indicating "never," 0.25 "sometimes," 0.5 "often,"0.75 "regularly," and 1 "always," leading to a maximum possible score of 8. A patient's score is empirically classified into three intervals: strong adherence = 0; average adherence = 1-2; low adherence = 3-8. 5. Mobile Application Usability Scale (MAUS): The scale measures mobile application usability which is formed with 10 constructs/factors which includes four items each (40 items at total). The scale measures using a 7-point Likert-type scale (1=strongly disagree...7=strongly agree) ### Conditions Module **Conditions:** - Neurogenic Bladder - Spinal Cord Injury - Intermittent Catheterization - Mobile Application **Keywords:** - neurogenic bladder - education - mobil application - compliance - quality of life ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** parallel group single-blind randomized control trial ##### Masking Info **Masking:** SINGLE **Masking Description:** The person doing the statistical analysis will not know which is the experiment and which is the control group. **Who Masked:** - PARTICIPANT **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 42 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** This group has routine CIC education. They fill the scales before discharge and 12. week after discharge. **Label:** control group(routine CIC education) **Type:** NO_INTERVENTION #### Arm Group 2 **Description:** This group has routine CIC education. Also mobile application uploaded their telephone before discharge. They fill the scales before discharge and 12. week after discharge. **Intervention Names:** - Device: mobile application on telephone **Label:** experimental group(routine CIC education+mobile application on telephone) **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - experimental group(routine CIC education+mobile application on telephone) **Description:** when patient discharge from the hospital, mobile application downloaded their telephone. then researcher give feedback about patients CIC outputs. also mobile application include 2 animations, videos, "frequently asked questions" and "ask the expert" section. **Name:** mobile application on telephone **Type:** DEVICE ### Outcomes Module #### Other Outcomes **Description:** The scale measures mobile application usability which is formed with 10 constructs/factors which includes four items each (40 items at total). The scale measures using a 7-point Likert-type scale (1=strongly disagree...7=strongly agree) **Measure:** Mobile Application Usability Scale (MAUS) **Time Frame:** Only the experimental group completes this scale 12 weeks after discharge. #### Primary Outcomes **Description:** This study want to evaluate quality of life with 2 scales. WHOQOL-BREF(World Health Organization Quality of Life Scale):The WHO Quality of Life Assessment (WHOQOL) is a generic quality of life instrument that was designed to be applicable to people living under different circumstances, conditions, and cultures. The short version known as WHOQOL-BREF with 26 items. Turkish version is 27 items. It is based on a Likert-type scale and is scored from 1 to 5, with higher scores indicating a better quality of life. **Measure:** 1. WHOQOL-BREF(World Health Organization Quality of Life questionnaire), **Time Frame:** Patients fill the scale "before discharge" and 12 weeks after discharge. **Description:** This is a 24-item self-administered questionnaire. Each item is scored on a 5-point Likert-type scale ranging from 0 (strongly disagree) to 4 (strongly agree), and after the conversion of the 14 reverse-coded items to give a common range of 0-100, the scores are calculated by multiplying the mean value of all items within each domain by 25. The total ISC-Q score is then calculated from the simple average from across the four domains (0-100), with higher scores indicating a higher quality of life. **Measure:** 2. Intermittent Self-Catheterization Questionnaire (ISC-Q) **Time Frame:** Patients fill the scale "before discharge" and 12 weeks after discharge. #### Secondary Outcomes **Description:** This study want to evaluate compliance with one scale. ICAS (IntermittentCatheterization Adherence Scale) is used to assess long-term patient adherence to prescribed ISC treatment. Binary answers were used for the first seven questions:yes = 1, no = 0, whereas the response options for the eighth question were graded on a 5-point Likert-type scale: 0 indicating "never," 0.25 "sometimes," 0.5 "often,"0.75 "regularly," and 1 "always," leading to a maximum possible score of 8. A patient's score is empirically classified in to three intervals: strong adherence = 0; average adherence = 1-2; low adherence = 3-8. **Measure:** Intermittent Catheterization Adherence Scale (ICAS) **Time Frame:** Patients fill the scale "before discharge" and 12 weeks after discharge. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * spinal cord injury patients, * The doctor has decided that the patient should undergo intermittent catheterization * Having received CIC training within the last month, * Having a phone with IOS/Android features, * Sending the surveys in the 12th week, the participants must be using the WhatsApp application to send the surveys. * being able to communicate, * sufficient manual dexterity, * having a body mass index below 30, * no vision problems, * turkish speech, * using single-use catheter Exclusion Criteria: * Having received IC training more than 1 month ago, * Individuals in the experimental group did not use the mobile application, * incompletely filled out forms, **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Ankara **Country:** Turkey **Facility:** Ankara Gaziler Physical Therapy and Rehabilitation Training and Research Hospital **State:** Çankaya **Zip:** 0000000 **Location 2:** **City:** Ankara **Country:** Turkey **Facility:** Ankara Gaziler Physical Therapy and Rehabilitation Training and Research Hospital **State:** Çankaya **Zip:** 680000 #### Overall Officials **Official 1:** **Affiliation:** Gazi University **Name:** NURCAN ÇALIŞKAN, Prof. Dr **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** SBÜ GAZİLER FİZİK TEDAVİ VE REHABİLİTASYON EĞİTİM VE ARAŞTIRMA HASTANESİ **Name:** BİLGE YILMAZ, Prof. Dr. **Role:** PRINCIPAL_INVESTIGATOR **Official 3:** **Affiliation:** SBÜ GAZİLER FİZİK TEDAVİ VE REHABİLİTASYON EĞİTİM VE ARAŞTIRMA HASTANESİ **Name:** Nilgün Aras, Phd student **Role:** STUDY_CHAIR ### IPD Sharing Statement Module **Description:** Since the study is still not finished, it was decided not to share it. **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000013118 - Term: Spinal Cord Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000020196 - Term: Trauma, Nervous System - ID: D000009461 - Term: Neurologic Manifestations - ID: D000001745 - Term: Urinary Bladder Diseases - ID: D000014570 - Term: Urologic Diseases - ID: D000052776 - Term: Female Urogenital Diseases - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases - ID: D000052801 - Term: Male Urogenital Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BXM - Name: Behaviors and Mental Disorders ### Condition Browse Module - Browse Leaves - ID: M15916 - Name: Spinal Cord Injuries - Relevance: HIGH - As Found: Spinal Cord Injury - ID: M5031 - Name: Urinary Bladder, Neurogenic - Relevance: HIGH - As Found: Neurogenic Bladder - ID: M17685 - Name: Wounds and Injuries - Relevance: HIGH - As Found: Injury - ID: M15915 - Name: Spinal Cord Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M22023 - Name: Trauma, Nervous System - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: M5026 - Name: Urinary Bladder Diseases - Relevance: LOW - As Found: Unknown - ID: M17319 - Name: Urologic Diseases - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M14127 - Name: Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M27095 - Name: Male Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: T6034 - Name: Quality of Life - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000013119 - Term: Spinal Cord Injuries - ID: D000001750 - Term: Urinary Bladder, Neurogenic - ID: D000014947 - Term: Wounds and Injuries ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429618 **Acronym:** PCOS **Brief Title:** Adolescent Polycystic Ovary Syndrome on a Low-carbohydrate Diet **Official Title:** Effect of a Low-carbohydrate Diet on Outcomes According to Phenotype in Juvenile Polycystic Ovary Syndrome #### Organization Study ID Info **ID:** 01/07 22.01.2024 #### Organization **Class:** OTHER **Full Name:** Etlik Zubeyde Hanım Women's Health Care, Training and Research Hospital ### Status Module #### Completion Date **Date:** 2024-08-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-06-04 **Type:** ACTUAL **Last Update Submit Date:** 2024-06-02 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2024-06-30 **Type:** ESTIMATED #### Start Date **Date:** 2024-05-30 **Type:** ESTIMATED **Status Verified Date:** 2024-06 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-18 **Study First Submit QC Date:** 2024-05-23 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Etlik Zubeyde Hanım Women's Health Care, Training and Research Hospital #### Responsible Party **Investigator Affiliation:** Etlik Zubeyde Hanım Women's Health Care, Training and Research Hospital **Investigator Full Name:** Mujde Can Ibanoglu **Investigator Title:** Assoc. Prof **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** The aim of the study was to investigate the changes in the clinical and biochemical parameters of adolescents on a low-carbohydrate diet in relation to their PCOS phenotype in the 3rd trimester. **Detailed Description:** Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder characterized by menstrual irregularities, anovulation, clinical and/or biochemical symptoms of hyperandrogenism (hirsutism and/or acne), micropolycystic ovaries, and metabolic abnormalities. In addition, some clinical and laboratory phenotypic features have been defined that were not previously included in the PCOS definition criteria, but which complement the clinical picture and influence the severity and morbidity of the clinical picture. Phenotype A: HA + OD + PCOM; phenotype B: HA + OD; phenotype C: HA + PCOM and phenotype D: OD + PCOM.For adult patients, internationally recognized diagnostic criteria have been developed based on combinations of otherwise unexplained hyperandrogenism, anovulation and polycystic ovary and are covered by the Rotterdam Consensus Criteria. However, in the adolescent age group, the frequency of anovulatory cycles and associated menstrual irregularities, the frequent symptoms of hyperandrogenism and acne vulgaris in the developmental phase, the problems with testosterone measurement and the prevalence of polycystic ovarian morphology in normal adolescents complicate the diagnosis. PCOS is a serious clinical and psychological problem for adolescent girls. Key interventions include lifestyle modification, including diet, physical activity and weight loss. These measures have been shown to alter the course of the disease in overweight and obese girls. In particular, it is known that high glycemic index carbohydrate intake and glycemic load lead to a rapid rise in blood glucose levels and increased insulin production. It is therefore thought that reducing the amount of insulin could have a more positive effect on PCOS than the usual carbohydrates. A low-carbohydrate diet is an effective, weight-independent approach in the treatment of metabolic disorders in PCOS patients. With this in mind, this study aimed to evaluate the clinical and biochemical outcomes at month 3 after application of the low-carbohydrate diet in adolescents according to their PCOS phenotype. ### Conditions Module **Conditions:** - Polycystic Ovary Syndrome - Adolescent Behavior - Diet Habit **Keywords:** - phenotype - polycystic ovary syndrome - adolescents - low carbonhydrate diet ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 60 **Type:** ESTIMATED **Patient Registry:** True **Study Type:** OBSERVATIONAL **Target Duration:** 3 Months ### Arms Interventions Module #### Arm Group 1 **Description:** PHENOTYPE A: Hyperandrogenism + Ovulatory Dysfunction + PCOM **Intervention Names:** - Dietary Supplement: Low carbonhydrate diet **Label:** Phenotype A #### Arm Group 2 **Description:** PHENOTYPE B: HA+OD **Intervention Names:** - Dietary Supplement: Low carbonhydrate diet **Label:** Phenotype B #### Arm Group 3 **Description:** PHENOTYPE C: HA+PCOM **Intervention Names:** - Dietary Supplement: Low carbonhydrate diet **Label:** Phenotype C #### Arm Group 4 **Description:** PHENOTYPE D: OD+PCOM **Intervention Names:** - Dietary Supplement: Low carbonhydrate diet **Label:** Phenotype D ### Interventions #### Intervention 1 **Arm Group Labels:** - Phenotype A - Phenotype B - Phenotype C - Phenotype D **Description:** Each patient will receive a 3-month low-carbohydrate (40% CHO) diet from the same dietitian. Whether the patients adhere to the diet and which components the prescribed diet consists of is recorded in detail. After 3 months of standard application, the patient is examined again by the gynecologist and obstetrician at the PCOS clinic. **Name:** Low carbonhydrate diet **Other Names:** - 0. - 3.month **Type:** DIETARY_SUPPLEMENT ### Outcomes Module #### Primary Outcomes **Description:** Age **Measure:** demographic datas on the study **Time Frame:** 3 months **Description:** Smoking **Measure:** Evaluation of demographic data **Time Frame:** 3 months **Description:** Body mass index Calculation of BMI: Height and body weight of the patients were measured using professionally calibrated devices. BMI was calculated using the formula BMI = weight (kg)/height (m)2. **Measure:** Demographic data at month 3 after application of a low-carbohydrate diet according to PCOS phenotypes in adolescents. **Time Frame:** 3 months **Description:** waist circumference(centimeters) **Measure:** Evaluation of clinical results at month 3 after application of a low-carbohydrate diet according to PCOS phenotypes in adolescents. **Time Frame:** 3 months **Description:** degree of hirsutism (Ferriman-Gallwey Hirsutism Scoring Scale; lowest 8 highest: 24) **Measure:** Evaluation of degree of hirsutism at month 3 after application of a low-carbohydrate diet according to PCOS phenotypes in adolescents. **Time Frame:** 3 months **Description:** prolactin (ng/mL) **Measure:** Hormone results at month 3 after application of a low-carbohydrate diet according to PCOS phenotypes in adolescents. **Time Frame:** 3 months **Description:** androstenedione (mosm/kg) **Measure:** androstenedione at month 3 after application of a low-carbohydrate diet according to PCOS phenotypes in adolescents. **Time Frame:** 3 months **Description:** dehydroepiandrosterone sulfate (DHEA-S) (μg/dL) **Measure:** dehydroepiandrosterone sulfate at month 3 after application of a low-carbohydrate diet according to PCOS phenotypes in adolescents. **Time Frame:** 3 months **Description:** thyroid stimulating hormone (TSH) (mIU/mL) **Measure:** TSH at month 3 after application of a low-carbohydrate diet according to PCOS phenotypes in adolescents. **Time Frame:** 3 months **Description:** Hormone test results : sex hormone-binding globulin (SHBG) **Measure:** SHBG at month 3 after application of a low-carbohydrate diet according to PCOS phenotypes in adolescents. **Time Frame:** 3 months **Description:** 17-OH progesterone (mIU/mL) **Measure:** 17-OH progesterone at month 3 after application of a low-carbohydrate diet according to PCOS phenotypes in adolescents. **Time Frame:** 3 months **Description:** free and total testosterone (ng/mL) **Measure:** Testosterone at month 3 after application of a low-carbohydrate diet according to PCOS phenotypes in adolescents. **Time Frame:** 3 months **Description:** Lipid profile: Total cholesterol (mg/dL), high-density lipoprotein (HDL) cholesterol (mg/dL), low-density lipoprotein (LDL) cholesterol (mg/dL), triglycerides (mg/dL). **Measure:** Lipid profile at month 3 after application of a low-carbohydrate diet according to PCOS phenotypes in adolescents. **Time Frame:** 3 months **Description:** fasting blood glucose **Measure:** Glucose at month 3 after application of a low-carbohydrate diet according to PCOS phenotypes in adolescents. **Time Frame:** 3 months **Description:** Calculation of insulin resistance: A fasting blood glucose level between 100-125 mg/dl was considered as 'impaired fasting glucose'. A Homeostatic Model Assessment Insulin Resistance (HOMA-IR) value of ≥2.5 was defined as insulin resistance. Insulin resistance was calculated using the formula of the homeostatic model. \[HOMA-IR= fasting glucose (mg/dl)xfasting insulin (mIU/mL)/405\]. **Measure:** Evaluation of insulin resistance at month 3 after application of a low-carbohydrate diet according to PCOS phenotypes in adolescents. **Time Frame:** 3 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * at least 1 year has passed since menarche * under 24 years old * patients who have not received an oral contraceptive method and have given verbal and written informed consent will be included. Exclusion Criteria: * over 24 years old * hyperprolactinemia, Cushing's syndrome, congenital adrenal hyperplasia, thyroid diseases * neuromuscular, liver, pancreatic or gastrointestinal diseases * hormonal medication such as antiandrogens, antidiabetics, glucocorticoids, insulin sensitizers or lipid regulators **Healthy Volunteers:** True **Maximum Age:** 24 Years **Minimum Age:** 12 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** FEMALE **Standard Ages:** - CHILD - ADULT **Study Population:** The study will be conducted based on the 2018 ESHRE/ASRM guideline: 1. Oligo and/or anovulation\* 2. Clinical and/or biochemical hyperandrogenism \*Oligo and/or anovulation are defined as follows: * It is considered normal in the first year after menarche as part of the pubertal transition * Between 1-3 years after menarche: \< 21 or \> 45 days * 3 years after menarche - perimenopause: \< 21 or \> 35 days or \< 8 cycles per year * 1 year after menarche: \>90 days for each menstrual cycle * Absence of menstruation at the age of 15 years or 3 years after menarche. Identification of phenotype groups: PHENOTYPE A: HA+ OD + PCOM PHENOTYPE B: HA+OD PHENOTYPE C: HA+PCOM PHENOTYPE D: OD+PCOM. ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Mujde Can Ibanoglu **Phone:** 05323089488 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Yaprak Engin-Ustun **Role:** CONTACT #### Overall Officials **Official 1:** **Affiliation:** Ankara Etlik Zubeyde Hanım Women's Health Training and Research Hospital, Ankara, Turkey. **Name:** Mujde Can Ibanoglu **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Joham AE, Pena AS. Polycystic Ovary Syndrome in Adolescence. Semin Reprod Med. 2022 Mar;40(1-02):e1-e8. doi: 10.1055/s-0042-1757138. Epub 2022 Sep 12. **PMID:** 36096151 **Citation:** Bozdag G, Mumusoglu S, Zengin D, Karabulut E, Yildiz BO. The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod. 2016 Dec;31(12):2841-2855. doi: 10.1093/humrep/dew218. Epub 2016 Sep 22. **PMID:** 27664216 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000004194 - Term: Disease - ID: D000010335 - Term: Pathologic Processes - ID: D000010048 - Term: Ovarian Cysts - ID: D000003560 - Term: Cysts - ID: D000009369 - Term: Neoplasms - ID: D000010049 - Term: Ovarian Diseases - ID: D000000291 - Term: Adnexal Diseases - ID: D000005831 - Term: Genital Diseases, Female - ID: D000052776 - Term: Female Urogenital Diseases - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases - ID: D000091662 - Term: Genital Diseases - ID: D000006058 - Term: Gonadal Disorders - ID: D000004700 - Term: Endocrine System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC04 - Name: Neoplasms - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: BC19 - Name: Gland and Hormone Related Diseases ### Condition Browse Module - Browse Leaves - ID: M16355 - Name: Syndrome - Relevance: HIGH - As Found: Syndrome - ID: M13970 - Name: Polycystic Ovary Syndrome - Relevance: HIGH - As Found: Polycystic Ovary Syndrome - ID: M6765 - Name: Cysts - Relevance: LOW - As Found: Unknown - ID: M12971 - Name: Ovarian Cysts - Relevance: LOW - As Found: Unknown - ID: M12972 - Name: Ovarian Diseases - Relevance: LOW - As Found: Unknown - ID: M3643 - Name: Adnexal Diseases - Relevance: LOW - As Found: Unknown - ID: M8943 - Name: Genital Diseases, Female - Relevance: LOW - As Found: Unknown - ID: M2876 - Name: Genital Diseases - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M14127 - Name: Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M9163 - Name: Gonadal Disorders - Relevance: LOW - As Found: Unknown - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000011085 - Term: Polycystic Ovary Syndrome - ID: D000013577 - Term: Syndrome ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429605 **Brief Title:** Evaluating the Efficacy and Safety of Preoperative Administration of Duloxetine for Pain Management in Women Undergoing Vaginal Hysterectomy. **Official Title:** Evaluating the Efficacy and Safety of Preoperative Administration of Duloxetine for Pain Management in Women Undergoing Vaginal Hysterectomy. #### Organization Study ID Info **ID:** Muğla-77 #### Organization **Class:** OTHER **Full Name:** Erzincan Military Hospital ### Status Module #### Completion Date **Date:** 2025-01-15 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-23 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2024-12-31 **Type:** ESTIMATED #### Start Date **Date:** 2024-05-20 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-15 **Study First Submit QC Date:** 2024-05-23 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Erzincan Military Hospital #### Responsible Party **Investigator Affiliation:** Erzincan Military Hospital **Investigator Full Name:** Kemal GUNGORDUK **Investigator Title:** MD. **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** Vaginal hysterectomy is the preferred route of choice for women desiring hysterectomy to treat uterine pathology, including premalignant conditions and fibroids. Compared with an abdominal or a laparoscopic approach, VH has been associated with a shorter recovery time and faster return to daily activities. However, management of postoperative pain still remains challenging for patients undergoing VH. Duloxetine is a serotonin-norepinephrine reuptake inhibitor commonly prescribed for the treatment of major depression and anxiety. Duloxetine also has been used in the treatment of chronic pain conditions, such as osteoarthritis and musculoskeletal pain In contrast, studies examining its use to ameliorate acute postoperative pain are limited to a single trial.12 More importantly, it remains to be determined whether perioperative duloxetine can improve the global quality of recovery after surgery. The study included the hypothesis that perioperative duloxetine would ease postoperative recovery in patients undergoing VH, and the Quality of Recovery-15 questionnaire (QoR-15) was to be used for evaluation ### Conditions Module **Conditions:** - Vaginal Hysterectomy - Postoperative Pain ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - INVESTIGATOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 80 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Only our clinic's standard preoperative and postoperative care were used (Güngördük K, Selimoğlu B, Gülseren V, Yasar E, Comba C, Özdemir İA. Effect of abdominal hot pack application on gastrointestinal motility recovery after comprehensive gynecologic staging surgery. Int J Gynaecol Obstet. 2024 Mar;164(3):1108-1116) **Label:** Control **Type:** NO_INTERVENTION #### Arm Group 2 **Description:** In addition to our standard clinical protocol, study patients were administered 60 mg oral duloxetine 2 hours before surgery and 24 hours after surgery **Intervention Names:** - Drug: duloxetine **Label:** Duloxetine **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Duloxetine **Description:** In addition to our standard clinical protocol, study patients were administered 60 mg oral duloxetine 2 hours before surgery and 24 hours after surgery **Name:** duloxetine **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** the level of abdominal pain during ambulation (according to VAS score) Since the visual analog scale (VAS) has been used in prior studies for evaluating similar outcomes \[10\], a 100-mm VAS was used to grade the level of pain. For assessing pain at rest, patients were asked to grade their level of pain from 0 (no pain) to 10 (worst pain ever experienced) at the abdomen and at the vagina while lying in bed. For assessing pain during ambulation, patients were asked to stand up, walk a few steps, and sit in a chair. Then, they were asked to grade their pain, using the same scale, during ambulation. **Measure:** The primary outcome **Time Frame:** 8 hours after surgery #### Secondary Outcomes **Description:** The QoR-15 is a 15-item questionnaire that measures the patient's QoR. Each item is answered on an 11-point numerical rating scale. The score ranges from 0 to 150 with a higher score indicating a better QoR. It measures in the domains of pain, physical comfort, physical independence, psychological support, and emotional state **Measure:** total QoR-15 score. **Time Frame:** on postoperative day 2 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients undergoing VH with or without bilateral salpingo-oophorectomy to gynecologic conditions and uterine size ≤12 weeks * American Society of Anesthesiologists grade 1-3 Exclusion Criteria: * patients with chronic non-gynecologic conditions (liver or renal or pulmonary disease or diabetes) -those using psychiatric drugs (antidepressants, neuroleptics, lithium) in the last 1 year, --- * those with duloxetine allergy * those using opioids for gynecologic or non-gynecologic conditions * additional concurrent abdominal/ laparoscopic procedures * Total vaginal prolapsus **Healthy Volunteers:** True **Maximum Age:** 75 Years **Minimum Age:** 20 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Kemal Güngördük **Phone:** 05057465266 **Role:** CONTACT ## Derived Section ### Condition Browse Module - Ancestors - ID: D000011183 - Term: Postoperative Complications - ID: D000010335 - Term: Pathologic Processes - ID: D000010146 - Term: Pain - ID: D000009461 - Term: Neurologic Manifestations ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases ### Condition Browse Module - Browse Leaves - ID: M13069 - Name: Pain, Postoperative - Relevance: HIGH - As Found: Postoperative Pain - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M14065 - Name: Postoperative Complications - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000010149 - Term: Pain, Postoperative ### Intervention Browse Module - Ancestors - ID: D000068760 - Term: Serotonin and Noradrenaline Reuptake Inhibitors - ID: D000014179 - Term: Neurotransmitter Uptake Inhibitors - ID: D000049990 - Term: Membrane Transport Modulators - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000018377 - Term: Neurotransmitter Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000000700 - Term: Analgesics - ID: D000018689 - Term: Sensory System Agents - ID: D000018373 - Term: Peripheral Nervous System Agents - ID: D000000928 - Term: Antidepressive Agents - ID: D000011619 - Term: Psychotropic Drugs - ID: D000015259 - Term: Dopamine Agents ### Intervention Browse Module - Browse Branches - Abbrev: Analg - Name: Analgesics - Abbrev: PsychDr - Name: Psychotropic Drugs - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: VaCoAg - Name: Vasoconstrictor Agents - Abbrev: CaAg - Name: Cardiotonic Agents ### Intervention Browse Module - Browse Leaves - ID: M299 - Name: Duloxetine Hydrochloride - Relevance: HIGH - As Found: Arm 1 - ID: M12575 - Name: Norepinephrine - Relevance: LOW - As Found: Unknown - ID: M15512 - Name: Serotonin - Relevance: LOW - As Found: Unknown - ID: M305 - Name: Serotonin and Noradrenaline Reuptake Inhibitors - Relevance: LOW - As Found: Unknown - ID: M20504 - Name: Neurotransmitter Agents - Relevance: LOW - As Found: Unknown - ID: M4032 - Name: Analgesics - Relevance: LOW - As Found: Unknown - ID: M4247 - Name: Antidepressive Agents - Relevance: LOW - As Found: Unknown - ID: M14474 - Name: Psychotropic Drugs - Relevance: LOW - As Found: Unknown - ID: M7473 - Name: Dopamine - Relevance: LOW - As Found: Unknown - ID: M17962 - Name: Dopamine Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000068736 - Term: Duloxetine Hydrochloride ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429592 **Brief Title:** Stress and Satisfaction Levels of Mothers According to Neuman's Systems Model on Stress and Satisfaction Levels of Mothers With Children in the Intensive Care Unit and Effective Decision Making **Official Title:** The Effect of the Empowerment Program Constructed According to Neuman's Systems Model on Stress and Satisfaction Levels of Mothers With Children in the Intensive Care Unit and Effective Decision Making #### Organization Study ID Info **ID:** gulsahogulerciyes4023640013 #### Organization **Class:** OTHER **Full Name:** TC Erciyes University ### Status Module #### Completion Date **Date:** 2024-10-15 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-23 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2024-09-15 **Type:** ESTIMATED #### Start Date **Date:** 2024-05-17 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-20 **Study First Submit QC Date:** 2024-05-23 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** TC Erciyes University #### Responsible Party **Investigator Affiliation:** TC Erciyes University **Investigator Full Name:** Gulsah Ogul **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Research; It will be carried out to examine the effect of the empowerment program structured according to the Neuman systems model on the stress and satisfaction levels and effective decision-making of mothers whose children are in the intensive care unit. **Detailed Description:** For pediatric nurses, supporting families, especially mothers, who take a primary role in care, increasing their ability to cope with the stress they experience, helping them access the information and resources they need, and supporting family functionality are vital parts of nursing care. In order to strengthen the family, the relationship between the nurse and the family must be based on respect and trust. In the nurse's communication with the family; The family should discuss the expectations of the family, discuss their views, and care about how much the family wants to be involved in care and what they want to do. Communication provided through these foundations helps to establish a trusting relationship between the family and the nurse and to determine boundaries with the parents. In this way, role confusion between the nurse and parent can be prevented and bidirectional satisfaction can be achieved. Another issue required to strengthen the family is to establish a close physical and emotional bond between the nurse and the family. This bond is related to the family feeling close enough to the nurse to open up to them not only in the presence of the problem, but also outside the problems. Thus, the family's trust in the nurse increases, removing the nurse from the position of healthcare personnel only caring for the child. Thanks to this special bond the nurse establishes with the family, it makes it easier for family members to express themselves and can even help them discover their weaknesses that they are not aware of. In addition, the nurse evaluates the family's coping methods, helps reveal their strengths, and can ensure more effective planning of care. Studies have shown that as a result of the empowerment programs applied by nurses to families, parents' depression and stress levels decrease, family function, self-efficacy, autonomy, problem-solving skills and family members' support for each other increases. In order to strengthen the family, it is of great importance to reduce the effects of internal and external stressors, holistic approach, increase the patient's perceptions and motivation, interact with the environment, reach, protect and maintain optimal health. In line with this purpose, the conceptual framework of nursing theories and models forms the basis and directs nursing education, management, practice and nursing research. These components are also included in the philosophical basis of the Neuman Systems Model. Neuman Systems Model is a model that focuses on human needs and emphasizes human uniqueness. It focuses on the multidimensional evaluation of the individual from a holistic perspective in achieving optimal health/well-being. However, accepting that the human being is a biopsychosocial being, it attaches importance to environmental stress and the health of the patient system that reacts to this stress. In Neuman's Systems Model, it is stated that when an individual is exposed to various stressors, his defense system is affected and the individual needs help to protect his basic structure. It is thought that nursing care structured in line with the Neuman Systems Model facilitates family and child-centered care practice. This study will be conducted to examine the effect of the empowerment program structured according to the Neuman systems model on the stress and satisfaction levels and effective decision-making of mothers whose children are in the intensive care unit. ### Conditions Module **Conditions:** - Nurse-Patient Relations **Keywords:** - Mother - Pediatric intensive care - Effective decision making - Satisfaction - Stres ### Design Module #### Design Info **Observational Model:** CASE_CONTROL **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 40 **Type:** ESTIMATED **Patient Registry:** True **Study Type:** OBSERVATIONAL **Target Duration:** 5 Days ### Arms Interventions Module #### Arm Group 1 **Description:** Data collection tools for mothers in the experimental group after acceptance of admission to the intensive care unit \[Descriptive Characteristics Form, Parental Stress Scale: (Pediatric Intensive Care Unit), Empowerment of Parents in The Intensive Care (EMPATHIC-30) (Empowerment of Parents in Intensive Care Scale), Decision Data will be collected using the Conflict in Making and Decision Making Confident Scale (KVÇS and KEOÖ). The prepared strengthening program will be applied for a total of 5 days starting from the first day of hospitalization. While the mothers are being treated, no other treatment will be done in the unit. Different time slots will be scheduled for each experiment. After the 5th day of the application was completed, data collection tools were used. **Intervention Names:** - Other: education **Label:** experimental group #### Arm Group 2 **Description:** Data collection tools from mothers in the control group after admission to the intensive care unit \[Descriptive Characteristics Form, Parental Stress Scale: (Pediatric Intensive Care Unit), Empowerment of Parents in The Intensive Care (EMPATHIC-30) (Empowerment of Parents in Intensive Care Scale), Decision Data will be collected using the Conflict in Making and Decision Making Confident Scale (KVÇS and KEOÖ). The routine operation of the intensive care unit will continue and data will be collected again after 5 days of hospitalization. **Intervention Names:** - Other: education **Label:** control group ### Interventions #### Intervention 1 **Arm Group Labels:** - control group - experimental group **Description:** nursing care practice **Name:** education **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** For mothers in the experimental group, data will be collected with data collection tools after acceptance of admission to the intensive care unit. The prepared strengthening program will be applied for a total of 5 days starting from the first day of hospitalization. While the treatments are being carried out to the mothers, no other treatments will be performed in the unit. Different time slots will be scheduled for each experiment. After the 5th day of the application is completed, data will be collected with data collection tools and mothers' stress levels and satisfaction levels will be evaluated. **Measure:** Mothers' stress levels and satisfaction levels will be evaluated. **Time Frame:** 3 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Research Inclusion Criteria; 1. Communicable, 2. Mothers whose children are admitted to the intensive care unit, 3. Mother must be over 18 years old 4. The child has a biological mother 5. Mothers who agreed to participate in the study and signed written consent forms, 6. The child's intensive care stay must be at least 5 days. Exclusion Criteria: * Criteria for Exclusion from the Study 1. Wanting to leave the study, 2. The child must have left the intensive care unit less than 5 days ago, 3. The mother is under 18 years of age. **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Mothers who want to voluntarily participate in the research ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** GULSAH OGUL **Phone:** 6177507711 **Role:** CONTACT #### Overall Officials **Official 1:** **Affiliation:** erciyes universitesi **Name:** oznur basdas, professor **Role:** STUDY_DIRECTOR ## Derived Section ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429579 **Brief Title:** Potts-shunt for the Treatment of Pediatric Patients With Severe Pulmonary Hypertension **Official Title:** Multicenter, Prospective, and Exploratory Study of Potts-shunt for the Treatment of Pediatric Patients With Severe Pulmonary Hypertension #### Organization Study ID Info **ID:** NCRC2024001 #### Organization **Class:** OTHER_GOV **Full Name:** China National Center for Cardiovascular Diseases ### Status Module #### Completion Date **Date:** 2029-04-23 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-23 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2029-04-23 **Type:** ESTIMATED #### Start Date **Date:** 2024-04-23 **Type:** ACTUAL **Status Verified Date:** 2024-04 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-05 **Study First Submit QC Date:** 2024-05-23 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER_GOV **Name:** China National Center for Cardiovascular Diseases #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** This is a multi-center, perspective, and exploratory study aimed at evaluating the 3-years clinical outcome of Potts-shunt procedure for pediatric patients with severe pulmonary artery hypertension (PAH). The included criteria are as followed: 1)6 months \< age ≤ 18 years; 2) ESC 2022 Group I PAH; 3) Have received standardized drug therapy for at least 6-9 months and still remain at intermediate to high/high-risk status of the criteria of ESC2022; 4) Presenting with significant clinical manifestations (i.e., progressive symptoms/syncope history/growth and development restriction, etc); 5) Informed consent form signed by the patient and their guardian. The excluded criteria are as followed: 1) ESC 2022 Group II-V PAH; 2) Poor right ventricular function: RVEF \< 25% or RVFAC \< 20%; 3) Deteriorated general condition: requiring ICU resuscitation or ECMO assistance; 4) Pulmonary artery pressure/main arterial pressure ratio \< 0.7; 5) Six-minute walk distance \< 150 meters (only applicable to patients aged 8 and above); 6) No significant improvement in RVEF under triple drug therapy. All of the pediatric patients with severe PAH who attend to pediatric cardiac outpatient clinic and meet the designed included criteria and excluded criteria will be enrolled in this study. All of the participants will be divided into two groups (Potts-shunt combined with conventional drug therapy group and only conventional drug therapy group) according to their individual health status (i.e., some contraindications of surgery) and their (or their parents') aspiration for Potts-shunts procedure. Follow-up is designed (eight-times follow-up) at the time of Potts-shunt procedure, post-operative ICU period, one month, three months, six months, one year, two years, and three years after Potts-shunt procedure or the rejection of Potts-shunt procedure. The items of follow-up include state of survival, whether or not have the lung transplantation (LTx), clinical manifestation, laboratory examination, function of right ventricle (detected by echocardiogram and cardiac magnetic resonance imaging), and the pulmonary circulation pressure (detected by right heart catheterization or Swan-Ganz catheterization). Primary outcome is the incidence rates of death or LTx three-years after Potts-shunt. Secondary outcomes are as followed: 1) Number and incidence rate of postoperative complications in patients undergoing Potts-shunt procedure; 2) Three-year WHO cardiac functional and 6-minute walk distance after Potts-shunt procedure; 3) the NT-ProBNP levels three-years after Potts-shunt procedure; 4) Right ventricular function on echocardiography three years after Potts-shunt procedure; 5) Right ventricular function on cardiac magnetic resonance imaging three years after Potts-shunt procedure; 6) Pulmonary circulation pressure measured by right heart catheterization or Swan-Ganz catheterization three years after Potts-shunt procedure; 7) Three-year mortality or LTx incidence rates after only conventional drug therapy. ### Conditions Module **Conditions:** - Pulmonary Artery Hypertension ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 120 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The comprehensive therapy included Potts-shunt procedure and conventional drug therapy (i.e., Prostacyclin analogues, PDE-5 inhibitors, and Endothelin receptor antagonists) **Intervention Names:** - Procedure: Comprehensive therapy combined Potts-shunt procedure and conventional drug therapy **Label:** Potts-shunt combined with conventional drug therapy group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Only admitted with conventional drug therapy (i.e., Prostacyclin analogues, PDE-5 inhibitors, and Endothelin receptor antagonists) **Intervention Names:** - Drug: Only conventional drug therapy **Label:** Only conventional drug therapy group **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Potts-shunt combined with conventional drug therapy group **Description:** Potts-shunt procedure is the surgery that connect the descending aorta and the left/main pulmonary artery by direct anastomosis, a Gore-tex tube or a Gore-tex tube with flap. **Name:** Comprehensive therapy combined Potts-shunt procedure and conventional drug therapy **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - Only conventional drug therapy group **Description:** Only conventional drug therapy (i.e., Prostacyclin analogues, PDE-5 inhibitors, and Endothelin receptor antagonists) **Name:** Only conventional drug therapy **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The incidence rates of death or lung transplantation 3 years after Potts-shunt, accessed by in-patient, out-patient, or telephone follow-up **Measure:** Mortality or Lung transplantation **Time Frame:** From the date of enrollment until the date of dear from any cause or lung transplantation, which ever came first, accessed up to 3 years #### Secondary Outcomes **Description:** Postoperative complications include hemoptysis, syncope, pulmonary hypertension crisis, low blood oxygen in the lower extremities etc. accessed by pediatric ICU doctors. **Measure:** Number and incidence rate of postoperative complications in patients undergoing Potts-shunt procedure **Time Frame:** From the date of enrollment to the date of any postoperative complications, whichever came first, accessed up to 3 years **Description:** WHO-FC was designed to measure the severity of pulmonary hypertension based on symptoms of dyspnea, fatigue, chest pain, and related syncope, accessed by the pediatric doctors. **Measure:** World Health Organization functional class (WHO-FC) after Potts-shunt procedure **Time Frame:** From the date of enrollment to the date of every view-point, assessed up to 3 years **Description:** NT-ProBNP (pg/ml) accessed by laboratory test **Measure:** NT-ProBNP levels after Potts-shunt procedure **Time Frame:** From the date of enrollment to the date of every view-point, assessed up to 3 years **Description:** The RVEF (%) accessed by cardiac MRI **Measure:** Right ventricular function on cardiac magnetic resonance imaging after Potts-shunt procedure **Time Frame:** From the date of enrollment to the date of every view-point, assessed up to 3 years **Description:** The RVFAC (%) accessed by echocardiography **Measure:** Right ventricular function on echocardiography after Potts-shunt procedure **Time Frame:** From the date of enrollment to the date of every view-point, assessed up to 3 years **Description:** SPAP, DPAP, MPAP (mmHg) etc. accessed by right heart catheterization or Swan-Ganz catheterization **Measure:** Pulmonary circulation pressure measured by right heart catheterization or Swan-Ganz catheterization after Potts-shunt procedure **Time Frame:** From the date of enrollment to the date of every view-point, assessed up to 3 years **Description:** The incidence rates of death or lung transplantation 3 years after enrollment **Measure:** Mortality or lung transplantation incidence rates after only conventional drug therapy **Time Frame:** From the date of enrollment until the date of dear from any cause or lung transplantation, which ever came first, accessed up to 3 years **Description:** The 6-minutes distance (meter) was designed to measure activity tolerance, accessed by pediatric doctors or parents of participants. **Measure:** The 6-minutes distance after Potts-shunt procedure **Time Frame:** From the date of enrollment to the date of every view-point, assessed up to 3 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. 6 months \&lt; age ≤ 18 years; 2. ESC 2022 Group I PAH; 3. Have received standardized drug therapy for at least 6-9 months and still remain at intermediate to high/high-risk status of the criteria of ESC2022; 4. Presenting with significant clinical manifestations (i.e., progressive symptoms/syncope history/growth and development restriction, etc); 5. Informed consent form signed by the patient and their guardian. Exclusion Criteria: 1. ESC 2022 Group II-V PAH; 2. Poor right ventricular function: RVEF \&lt; 25% or RVFAC \&lt; 20%; 3. Deteriorated general condition: requiring ICU resuscitation or ECMO assistance; 4. Pulmonary artery pressure/main arterial pressure ratio \&lt; 0.7; 5. Six-minute walk distance \&lt; 150 meters (only applicable to patients aged 8 and above); 6. No significant improvement in RVEF under triple drug therapy. **Maximum Age:** 18 Years **Minimum Age:** 6 Months **Sex:** ALL **Standard Ages:** - CHILD - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Shoujun Li, MD **Phone:** +8613501071589 **Role:** CONTACT #### Locations **Location 1:** **City:** Beijing **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Shoujun Li, MD - **Phone:** +8613501071589 - **Role:** CONTACT **Country:** China **Facility:** Pediatric cardic surgical center, Fuwai Hospital **State:** Beijing **Status:** RECRUITING **Zip:** 100037 ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10024 - Name: Hypertension - Relevance: HIGH - As Found: Hypertension - ID: M2261 - Name: Pulmonary Arterial Hypertension - Relevance: HIGH - As Found: Pulmonary Artery Hypertension - ID: M10027 - Name: Hypertension, Pulmonary - Relevance: HIGH - As Found: Pulmonary Hypertension - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: T4807 - Name: Pulmonary Arterial Hypertension - Relevance: HIGH - As Found: Pulmonary Artery Hypertension ### Condition Browse Module - Meshes - ID: D000006976 - Term: Hypertension, Pulmonary - ID: D000081029 - Term: Pulmonary Arterial Hypertension - ID: D000006973 - Term: Hypertension ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: AnAg - Name: Antihypertensive Agents - Abbrev: PlAggInh - Name: Platelet Aggregation Inhibitors - Abbrev: VaDiAg - Name: Vasodilator Agents ### Intervention Browse Module - Browse Leaves - ID: M30466 - Name: Endothelin Receptor Antagonists - Relevance: LOW - As Found: Unknown - ID: M29332 - Name: Phosphodiesterase 5 Inhibitors - Relevance: LOW - As Found: Unknown - ID: M14328 - Name: Epoprostenol - Relevance: LOW - As Found: Unknown - ID: M262431 - Name: Tezosentan - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429566 **Brief Title:** Safety and Efficacy Study of GB001 Recombinant Peptide Spray in Subjects With Mild Recurrent Aphthous Ulcers **Official Title:** A Multicenter, Randomized, Double-blind, Placebo-controlled Phase IIa Clinical Trial to Evaluate the Efficacy and Safety of Oral Local Use of GB001 Recombinant Peptide Spray for the Treatment of Mild Recurrent Aphthous Ulcer #### Organization Study ID Info **ID:** YK2019L01P-IIa #### Organization **Class:** INDUSTRY **Full Name:** Zhejiang Echon Biopharm Limited ### Status Module #### Completion Date **Date:** 2024-07-10 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-06-03 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-31 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2023-12-06 **Type:** ACTUAL #### Start Date **Date:** 2023-07-18 **Type:** ACTUAL **Status Verified Date:** 2024-04 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-04-30 **Study First Submit QC Date:** 2024-05-22 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Zhejiang Echon Biopharm Limited #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** This trial is conducted in China. The purpose is to evaluate the efficacy, Pharmacokinetics (PK) profile, immunogenicity and safety of GB001 recombinant peptide spray in adults with mild recurrent aphthous ulcer. ### Conditions Module **Conditions:** - Healthy ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 120 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Each subject will take oral GB001 recombinant peptide spray 4 times a day, 4 sprays each time, no more than 29 times，The dosage of the group is 0.108mg/spray. **Intervention Names:** - Drug: GB001 recombinant peptide spray low dose group、high dose group **Label:** GB001 recombinant peptide spray low dose group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Each subject will take oral GB001 recombinant peptide spray 4 times a day, 4 sprays each time, no more than 29 times，The dosage of the group is 0.216mg/spray. **Intervention Names:** - Drug: GB001 recombinant peptide spray low dose group、high dose group **Label:** GB001 recombinant peptide spray high dose group **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Each subject will take oral GB001 recombinant peptide spray 4 times a day, 4 sprays each time, for 8 days. **Intervention Names:** - Drug: GB001 recombinant peptide spray placebo **Label:** Placebo group **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - GB001 recombinant peptide spray high dose group - GB001 recombinant peptide spray low dose group **Description:** Administrated oral spray. Each subject will take oral GB001 recombinant peptide spray 4 times a day, 4 sprays each time, no more than 29 times，The dosage of the group is 0.108mg/spray for low dose group and 0.216mg/spray for high dose group. **Name:** GB001 recombinant peptide spray low dose group、high dose group **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo group **Description:** Administrated oral spray.Each subject will take oral GB001 recombinant peptide spray placebo 4 times a day, 4 sprays each time, no more than 29 times **Name:** GB001 recombinant peptide spray placebo **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Ulcer healing was defined as disappearance of pain and zeroing of ulcer size. At the screening visit the ulcer area and pain severity of patient to clinical examination will be rated at baseline. The patients will be self-assessment pain severity in vas score sheet every day . And the patients will be re-examined in day 6 to assess the ulcer area by periodontal probe. **Measure:** Target ulcer healing rate for patients in day 6 **Time Frame:** Day 6 **Measure:** Subjects self-rated the time it took for irritation pain to disappear **Time Frame:** Day 8 #### Secondary Outcomes **Description:** Ulcer healing was defined as disappearance of pain and zeroing of ulcer size.The patients will be self-assessment pain severity in vas score sheet every day . And the patients will be re-examined to assess the ulcer area by periodontal probe. **Measure:** Time for target ulcer to heal **Time Frame:** Day 8 **Description:** Ulcer healing was defined as disappearance of pain and zeroing of ulcer size. At the screening visit the ulcer area and pain severity of patient to clinical examination will be rated at baseline. The patients will be self-assessment pain severity in vas score sheet every day . And the patients will be re-examined in day 4 and day 8 to assess the ulcer area by periodontal probe. **Measure:** Targeted ulcer healing rate for patients in day 4 and day 8 **Time Frame:** Day 4,Day 8 **Description:** At the screening visit the ulcer area of patient to clinical examination will be rated at baseline. And the patients will be re-examined in day 4、day 6 and day 8 to assess the ulcer area by periodontal probe. **Measure:** Changes in target ulcer area relative to baseline **Time Frame:** Day 4,Day 6,Day 8 **Measure:** Self evaluation of pain disappearance rate and relief rate **Time Frame:** Day 4,Day 6,Day 8 **Description:** Apparent terminal phase half-life **Measure:** Pharmacokinetics Characteristics， t½ of GB001 Recombinant Peptide **Time Frame:** Day 1,Day 4 **Description:** Area under the plasma concentration versus time curve **Measure:** Pharmacokinetics Characteristics，AUC of GB001 Recombinant Peptide **Time Frame:** Day 1,Day 4 **Description:** Maximum plasma concentration **Measure:** Pharmacokinetics Characteristics， Cmax of GB001 Recombinant Peptide **Time Frame:** Day 1,Day 4 **Description:** Time of maximum plasma concentration **Measure:** Pharmacokinetics Characteristics， Tmax of GB001 Recombinant Peptide **Time Frame:** Day 1,Day 4 **Measure:** Immunogenicity(drug resistant antibody (ADA)) **Time Frame:** Day 1,Day 14,Day 28 **Measure:** Incidence of Adverse Events **Time Frame:** First dose to last visit,an average of 1 month. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. It meets the diagnostic criteria for mild recurrent Aphthous ulcer in the fifth edition of Oral Mucosa published by People's Medical Publishing House in 2020. 2. 18≤ age ≤65 years old, gender is not limited. 3. Patients with untreated target ulcer onset ≤48 hours at the time of screening. 4. VAS score of target ulcer irritation pain ≥3 points, 2mm≤ length diameter of target ulcer ≤10mm. 5. Subjects and their sexual partners agree to use effective contraception during the study period and for at least 30 days after the study ends. 6. Sign a written informed consent, and be able to comply with the visit and related procedures stipulated in the program. Exclusion criteria: 1. The diagnosis was severe aphthous ulcer, herpetic aphthous ulcer, acute herpetic gingivitis stomatitis, traumatic ulcer, cancerous ulcer, tuberculous ulcer, syphilitic ulcer, necrotic salivate metaplasia, Behcet disease and other diseases or drug induced ulcers. 2. Patients with suppurative tonsillitis or other painful lesions in the mouth, such as pericoronitis, pulpitis, periapical inflammation, etc., affecting the pain score of target ulcer. 3. Target ulcer is affected by residual root, residual crown, denture, prosthesis, orthodontic device and other stimulating factors in the corresponding parts of the target ulcer. 4. The ulcer is located in the lingual frenulum, the back wall of the pharynx and other parts, and its size is not easy to measure. 5. Those who plan to perform other oral treatments during the trial that affect the determination of drug effectiveness and safety. 6. Smokers \> 20 cigarettes/day or betel nut lovers in the past 3 months. 7. People who have used painkillers or drugs that may affect the efficacy of pain observation within 24 hours before the first administration, such as sedatives, anti-allergy drugs, non-steroidal anti-inflammatory drugs, etc. 8. Patients who have used antibiotics or antiviral drugs locally or systematically within 1 week before screening. 9. Patients who had used immunosuppressive agents locally within 1 week before screening or systemic immunosuppressive agents within 2 weeks before screening. 10. Patients with oral local or systemic use of glucocorticosteroids within 4 weeks prior to screening. 11. Patients who have taken anticholinergic drugs to reduce salivary secretion within 2 weeks prior to screening. 12. Complicated with severe liver and kidney diseases, or abnormal liver and kidney function tests (ALT and AST≥ 1.5 times the upper limit of normal, SCr \> the upper limit of normal). 13. Patients with severe anemia (Hb \< 60g/L). 14. Complicated with severe heart and lung disease, uncontrolled diabetes (fasting blood glucose \> 7.0mmol/L or random blood glucose ≥11.1mmol/L), advanced tumors, diseases of the blood and hematopoietic system, or other serious or progressive diseases of the system. 15. Known or suspected allergic history or serious adverse reactions to the experimental drug and its excipients. 16. Pregnant or lactating women and those with recent pregnancy plans. 17. Participants who had participated in other interventional clinical trials within 3 months prior to screening. 18. Other conditions deemed inappropriate by the investigator for participation in the study. **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Changsha **Country:** China **Facility:** The First Hospital of Hunan University of Chinese Medicine **State:** Hunan **Zip:** 410000 ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000013280 - Term: Stomatitis - ID: D000009059 - Term: Mouth Diseases - ID: D000009057 - Term: Stomatognathic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC07 - Name: Mouth and Tooth Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M14850 - Name: Recurrence - Relevance: LOW - As Found: Unknown - ID: M17206 - Name: Ulcer - Relevance: LOW - As Found: Unknown - ID: M16071 - Name: Stomatitis, Aphthous - Relevance: HIGH - As Found: Aphthous Ulcer - ID: M16070 - Name: Stomatitis - Relevance: LOW - As Found: Unknown - ID: M12019 - Name: Mouth Diseases - Relevance: LOW - As Found: Unknown - ID: M12017 - Name: Stomatognathic Diseases - Relevance: LOW - As Found: Unknown - ID: T455 - Name: Aphthous Stomatitis - Relevance: HIGH - As Found: Aphthous Ulcer ### Condition Browse Module - Meshes - ID: D000013281 - Term: Stomatitis, Aphthous ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429553 **Brief Title:** Minimally Invasive Intracranial Hematoma Aspiration for Spontaneous Intracerebral Hemorrhage **Official Title:** A Multicenter Randomized Controlled Clinical Study of Minimally Invasive Intracranial Hematoma Aspiration and Drainage Combined With Urokinase Injection and Drug Therapy for Spontaneous Intracerebral Hemorrhage #### Organization Study ID Info **ID:** 2023KY135 #### Organization **Class:** OTHER_GOV **Full Name:** Anhui Provincial Hospital ### Status Module #### Completion Date **Date:** 2025-06-30 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-23 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-06-30 **Type:** ESTIMATED #### Start Date **Date:** 2023-07-01 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-05 **Study First Submit QC Date:** 2024-05-23 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER_GOV **Name:** Anhui Provincial Hospital #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** To observe the effect of minimally invasive intracranial hematoma aspiration and drainage combined with urokinase injection and drug therapy on prognosis of spontaneous cerebral hemorrhage. **Detailed Description:** Intracerebral hemorrhage (ICH) refers to the spontaneous rupture of large and small arteries, veins, and capillaries in the brain caused by various reasons under non-traumatic conditions. Hypertension is the most common predisposing factor for intracerebral hematoma, and the risk increases with age. The challenge in surgical hematoma evacuation lies in the potential for surgical complications to negate the benefits of hematoma removal. Surgical treatment is generally considered only when the supratentorial hematoma causes a life-threatening space-occupying effect. Therefore, the size of the intracerebral hematoma is a key factor in determining whether surgery can bring benefits to patients. Specifically, intracerebral hematomas with a volume less than 30 ml are considered small and medium-sized. Previously, drug-based conservative treatment was often the first choice for small and medium-sized intracerebral hematomas. However, with the accumulation of clinical data, it has been found that while these patients have low blood loss and mortality, their neurological function impairment is significant, and the recovery of neurological function under conservative treatment is often suboptimal. Therefore, some scholars have suggested the use of adjunctive surgical options for small and medium-sized intracerebral hematomas, such as small craniotomy, craniotomy, endoscopic surgery, fibrinolytic therapy combined with hematoma aspiration, and CT-guided stereotactic aspiration (i.e., minimally invasive surgery). ### Conditions Module **Conditions:** - Spontaneous Cerebral Hemorrhage **Keywords:** - Spontaneous cerebral hemorrhage - intracranial hematoma aspiration - urokinase ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 100 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Minimally invasive hematoma aspiration drainage combined with urokinase injection **Intervention Names:** - Procedure: Minimally invasive hematoma aspiration drainage combined with urokinase injection **Label:** Hematoma puncture group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Drug conserved group **Intervention Names:** - Procedure: Minimally invasive hematoma aspiration drainage combined with urokinase injection **Label:** Drug conserved group **Type:** SHAM_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Drug conserved group - Hematoma puncture group **Description:** Minimally invasive hematoma aspiration drainage combined with urokinase injection **Name:** Minimally invasive hematoma aspiration drainage combined with urokinase injection **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** Modified Rankin Scale score (mRS)（0-6）（ higher scores mean a worse outcome.） **Measure:** Modified Rankin Scale score (mRS)（0-6）（ higher scores mean a worse outcome.） **Time Frame:** 6 months #### Secondary Outcomes **Description:** volume of hematoma **Measure:** volume of hematoma **Time Frame:** 2 weeks **Description:** National Institutes of Health Stroke Scale（NIHSS)（0-42）（ higher scores mean a better outcome.） **Measure:** National Institutes of Health Stroke Scale（NIHSS)（0-42）（ higher scores mean a better outcome.） **Time Frame:** 6 months **Description:** Muscle strength classification change（0-5）（ higher scores mean a better outcome.） **Measure:** Muscle strength classification change（0-5）（ higher scores mean a better outcome.） **Time Frame:** 6 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Aged 18-80 years; 2. ICH in the basal ganglia was diagnosed by CT examination of the head (bleeding mainly from the caudate nucleus, lentiform nucleus, clavate nucleus or amygdala); 3. Based on CT examination of the head, the volume of hematoma was calculated to be 20-40 mL, and the midline structure was shifted horizontally in the pineal gland \< 3 mm; The calculation formula of hematoma volume V (cm3) = A\*B\*C\*1/2, where A is the longest diameter (cm) of the largest level of hematoma in the horizontal CT scan, B is the widest diameter (cm) of the hematoma in the plane perpendicular to A, and C is the thickness (cm) of the hematoma in the CT film; 4. The time from onset to randomization is within 48 hours; 5. GCS score 4-14 points during randomization; 6. NIHSS score \>= 6 points during randomization; 7. Muscle strength of unilateral limbs on the symptomatic side is grade 0-3; 8. mRS0-1 score before onset; 9. Systolic blood pressure was controlled below 180mmHg before randomization; 10. Written informed consent signed by the patient and his legal representative. Exclusion Criteria: 1. Bleeding in other areas (such as the thalamus, brain stem, or cerebellum); 2. Bleeding caused by other causes (such as aneurysm, arteriovenous malformation, brain trauma, brain tumor, hemorrhage transformation of massive cerebral infarction, hemorrhage caused by amyloidosis, hemorrhage caused by coagulation disorder) or combined with aneurysm, arteriovenous malformation, brain trauma, brain tumor, massive cerebral infarction, amyloidosis, severe coagulation disorder; 3. Recent history of cerebral hemorrhage (\< 1 year); 4. Multiple intracranial hemorrhage; 5. The CTA source map indicated early signs of expanded intracerebral hemorrhage hematoma (point sign), and the possibility of progressive hemorrhage was largely ruled out; 6. Patients with ventricular hemorrhage or ICH intrusion into the ventricle should be considered for external ventricular drainage; 7. Any history of parenchyma or other intracranial subarachnoid, subdural or epidural blood and surgical history within the last 30 days; 8. Patients with coagulation dysfunction such as hereditary or acquired bleeding constitution and lack of coagulation factor; 9. Hemoglobin \< 100 g/L, hematocrit \< 25%, platelet count \< 100\*10\^9/L; 10. Were receiving anticoagulant drugs such as warfarin, dabigatran or rivaroxaban within one week before enrollment, with INR \> 1.4; 11. Long-term anticoagulant and antiplatelet therapy is expected; 12. There is a history of internal bleeding, such as digestive tract bleeding, urogenital system bleeding, respiratory tract bleeding is not completely controlled; 13. Myocardial infarction within the last 30 days; 14. Known high risk of embolism, including patients with mechanical heart valve implantation, history of left heart thrombosis, mitral stenosis with atrial fibrillation, acute pericarditis, or subacute bacterial endocarditis. Atrial fibrillation without mitral stenosis is suitable; 15. Severe liver function damage, ALT \> 3 times the upper limit of normal, or AST \> 3 times the upper limit of normal. Severe renal insufficiency, glomerular filtration rate \< 30 ml/min/1.73m2; 16. Hypertension that could not be effectively controlled by active antihypertensive therapy before randomization (systolic blood pressure was still greater than 180 mmHg); 17. Patients with Alzheimer's disease or mental illness are unable to complete the follow-up plan as required; 18. Combined with any serious diseases that may be assessed to interfere with the test results: including diseases of the respiratory system, circulatory system, digestive system, genitourinary system, endocrine system, immune system and blood system; 19. Those who currently have drug or alcohol abuse or dependence and are expected to have poor compliance and difficulty in completing follow-up; 20. Allergic to urokinase or surgery-related drugs and instruments; 21. Pregnant or lactating women, or those planning to become pregnant within one year; 22. Life expectancy of \< 12 months due to advanced stage of any disease; 23. Are participating in other clinical trials or have been included in this trial in the previous stage; 24. The patient or his legal guardian is not willing to sign a written informed consent (YNMT). **Maximum Age:** 80 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Hefei **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Hao Xu, PhD - **Phone:** +8618019576586 - **Role:** CONTACT **Country:** China **Facility:** Hao Xu **State:** Anhui **Status:** RECRUITING **Zip:** 230001 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000020300 - Term: Intracranial Hemorrhages - ID: D000002561 - Term: Cerebrovascular Disorders - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC14 - Name: Heart and Blood Diseases ### Condition Browse Module - Browse Leaves - ID: M9556 - Name: Hemorrhage - Relevance: HIGH - As Found: Hemorrhage - ID: M5792 - Name: Cerebral Hemorrhage - Relevance: HIGH - As Found: Cerebral Hemorrhage - ID: M9493 - Name: Hematoma - Relevance: HIGH - As Found: Hematoma - ID: M22113 - Name: Intracranial Hemorrhages - Relevance: LOW - As Found: Unknown - ID: M5810 - Name: Cerebrovascular Disorders - Relevance: LOW - As Found: Unknown - ID: M5204 - Name: Brain Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002543 - Term: Cerebral Hemorrhage - ID: D000006470 - Term: Hemorrhage - ID: D000006406 - Term: Hematoma ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429540 **Brief Title:** Post Extraction Changes Following Ridge Preservation Using Partially Demineralized Dentin Block Versus Xenograft **Official Title:** Evaluation of Post Extraction Hard Tissue Alteration Following Ridge Preservation Using Partially Demineralized Dentin Block Versus Xenograft in the Esthetic Zone: A Randomized Controlled Clinical Trial #### Organization Study ID Info **ID:** 12224PER6-3-1 #### Organization **Class:** OTHER **Full Name:** Cairo University ### Status Module #### Completion Date **Date:** 2024-12-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-29 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-24 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-07-01 **Type:** ESTIMATED #### Start Date **Date:** 2024-03-01 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Cairo University #### Responsible Party **Investigator Affiliation:** Cairo University **Investigator Full Name:** Danah Tayseer Al Ghothani **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The aim of this study is to clinically and radiographically evaluate the dimensional changes of hard tissue after using Partially Demineralized Dentin Block versus Xenograft in the esthetic zone. The main question: In patients with unrestorable teeth, will the use of partially demineralized Dentin Block be more effective than Xenograft in preserving vertical and horizontal ridge dimensions? After enrollment, a thorough preoperative assessment, including history taking, clinical, and radiographic examinations, will be conducted. Initial therapy includes periodontal treatment (phase 1 therapy) followed by random assignment to one of two treatment groups: ridge preservation using Partially Demineralized Dentin Block or Xenograft. Both groups will undergo atraumatic extraction. For the test group, an autogenous partially demineralized dentin graft will be prepared, involving tooth cleaning, grinding, and partial demineralization with the Tooth Transformer device, followed by Leukocyte-Platelet Rich Fibrin (L-PRF) membrane and liquid fibrinogen preparation. The L-PRF membranes will be cut, mixed with dentin particles, and combined with liquid fibrinogen to form a compact graft. The block will be placed inside the socket and covered by an L-PRF membrane and secured with a cross-suture. In the control group, Xenograft will be used, and the socket filled with deproteinized bovine bone mineral, covered with a collagen membrane, and secured with a cross-suture. After a healing period of 6 months, at the time of implant placement, a biopsy will be taken using a trephine bur. **Detailed Description:** Objective of the study: The aim of this study is to evaluate post extraction hard tissue changes following ridge preservation using Partially Demineralized Dentin Block versus Xenograft in the esthetic zone. Research Procedure: Patients will be selected from the outpatient clinic of the Oral Medicine and Periodontology Department, Faculty of Dentistry, Cairo University. General operative procedures: Patients who fulfill the inclusion criteria will be enrolled. The nature of the study will be explained to each patient, as well as the importance of compliance with pre- and post-operative instructions and follow-up visits. Preoperative preparation: A thorough preoperative assessment of all patients will be carried out, including history taking, clinical examination, and radiographic examination. History: Each patient will be interviewed to obtain a comprehensive history. Clinical examination: Proper intraoral examination will be done to evaluate the following parameters for the tooth of interest: 1) Restorability of the tooth. 2) Periodontal condition of the tooth to be extracted and the adjacent teeth. Radiographic examination: 1. Periapical radiographs will be done to rule out the presence of any periapical infection and evaluate the presence of caries or periodontal disease in the adjacent teeth. 2. In cases that meet the inclusion criteria, cone beam computed tomography (CBCT) will be taken at three time points: before the surgery, immediately after socket preservation, and after 6 months. The CBCT before the surgery will be used to assess the type of socket, while the baseline CBCT immediately after socket preservation will be used to evaluate the horizontal ridge width at 1, 3, and 5 mm below the most coronal aspect of the crest, and buccal and palatal ridge height. The CBCT taken after 6 months will serve to superimpose the two scans and assess long-term changes. Initial Therapy: The initial therapy will consist of periodontal treatment (phase I therapy) including supragingival scaling, subgingival debridement if needed, adjustment of faulty restorations, and polishing. Mechanical plaque control instructions for each patient include brushing and interdental cleaning techniques. Patients will be randomly assigned to one of the treatment groups: * Test Group: Ridge preservation using Partially Demineralized Dentin Block in the esthetic zone. * Control Group: Ridge preservation using Xenograft in the esthetic zone. Surgical Procedure: Atraumatic extraction: * The patient will rinse with 0.12% Chlorhexidine (Hexitol, ADCO Pharma Co, Egypt). * The operator will administer 4% articaine hydrochloride with 1:100,000 epinephrine (Septodent Co. for Pharmaceuticals, France). * Flapless and atraumatic tooth extraction will be initiated by making an intrasulcular incision using a 15c blade. * Next, a periotome will be used to sever the periodontal ligament (PDL) fibers, followed by the use of a straight elevator and extraction forceps for the extraction process. In the test group, the autogenous partially demineralized dentin graft will be prepared as follows: A high-speed fine finishing stone and saline irrigation will be used to clean the tooth and remove any decay, restoration, or foreign materials. The tooth will be rinsed twice in phosphate buffered saline. The tooth will be dried using air, then ground and partially demineralized with the Tooth Transformer device following the manufacturer's protocol. Dentin particles will be obtained with dimensions of 400 - 800 μm. Dentin block preparation: During the preparation of partially demineralized dentin, Leukocyte-Platelet Rich Fibrin (L-PRF) membranes will also be prepared. Vacutainer tubes without anticoagulant (red cap, glass coating) will be used to collect four 10-cc blood samples, which will then be immediately centrifuged at 2700 rpm for 12 minutes using the IntraSpin centrifuge (IntraLock, Florida, USA). Additionally, two extra blood samples will be collected in 9-cc non-coated vacutainer tubes without anticoagulants (white cap). These samples will be centrifuged at 2700 rpm for 3 minutes. The resulting yellow fluid (liquid fibrinogen) at the top of the white cap tubes will be carefully aspirated using a sterile syringe, while avoiding red blood cells. The L-PRF clots obtained after 12 minutes of centrifugation will be placed in the Xpression box (IntraSpin, Intra-Lock, Florida, USA) for 5 minutes to allow gentle compression (by gravity) into membranes. To prepare the L-PRF block, the L-PRF membranes will be cut into small pieces and mixed with the dentin particles at a ratio of 2 membranes to 0.5 g of dentin, providing a 1:1 volume ratio. The liquid fibrinogen will be added to the homogeneous mixture, and while shaping the mixture into the desired form, it will be gently stirred for approximately 10 seconds. Within a few minutes, the fibrinogen will convert into fibrin primarily from the activated blood platelets in the chopped L-PRF membranes. This process will effectively trap the biomaterial and the L-PRF pieces, forming a sturdy block known as the "dentin block," which serves as a convenient and compact graft. Alveolar ridge preservation: Following a thorough cleaning procedure, the sockets will be carefully packed with customized "dentin blocks" that are shaped to match the individual size and contours of each socket. Once the grafts are properly adapted to the sockets, they will be covered with two layers of L-PRF membranes, which will extend approximately 2 mm along the entire envelope formed between the periosteum and the bony boundaries of the sockets (in a 360° fashion). To ensure stability and prevent displacement, the wounds will be secured using non-resorbable sutures. It's important to note that the purpose of the sutures is to maintain the position of the grafts and membranes rather than closing the wounds entirely. In the control group: The same extraction and socket debridement procedure will be performed. Following that, the extraction socket will be thoroughly filled with deproteinized bovine bone mineral, and a collagen membrane will be employed to cover the socket. The membrane will be shaped to extend 2-3 mm beyond the margins of the extraction socket and positioned just beneath the marginal mucosa. To ensure its stability, a cross-suture will be performed, securing the membrane in place. The sutures will be removed two weeks after the surgery. Biopsy collection: After a healing period of 6 months, at the time of implant placement, a biopsy will be taken from the central area of the grafted site using a 3-mm trephine bur. The biopsy will be promptly fixed in 10% neutral buffered formalin, followed by dehydration through a series of alcohol baths with increasing concentrations (ranging from 50% to 100%). Subsequently, the specimen will be embedded in paraffin. Finally, a tissue section with a thickness of 4 μm will be prepared and subjected to hematoxylin-eosin staining for subsequent histological analysis. Outcomes: Radiographic vertical buccal bone changes, vertical palatal bone changes, horizontal bone changes, percentage of new vital bone formation, percentage of residual bone graft, and implant primary stability ### Conditions Module **Conditions:** - Socket Preservation **Keywords:** - L-PRF - Xenograft - Collagen membrane - Dentin block - Partially demineralized dentin block - Socket preservation - Liquid fibrinogen ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** A Randomized Controlled Clinical Trial ##### Masking Info **Masking:** SINGLE **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 22 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The Partially Demineralized Dentin Block will be prepared using the Tooth Transformer device to grind the extracted tooth and partially demineralize it. Leukocyte-Platelet Rich Fibrin (L-PRF) and liquid fibrinogen will then be added to create a block graft. **Intervention Names:** - Biological: Partially Demineralized Dentin Block **Label:** Partially Demineralized Dentin Block **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** The Xenograft procedure will involve filling the socket with deproteinized bovine bone mineral, followed by the placement of a collagen membrane to cover the socket **Intervention Names:** - Biological: Xenograft **Label:** Xenograft **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Partially Demineralized Dentin Block **Description:** The extracted tooth will be dried using air, then ground and partially demineralized with the Tooth Transformer device following the manufacturer's protocol. Dentin particles will be obtained with dimensions of 400-800 μm. The partially demineralized dentin will then be prepared by cutting the Leukocyte-Platelet Rich Fibrin (L-PRF) membranes into small pieces and mixing them with the dentin particles. Liquid fibrinogen will be added to the homogeneous mixture. Within a few minutes, the fibrinogen will convert into fibrin primarily from the activated blood platelets in the chopped L-PRF membranes. This process will effectively trap the biomaterial and the L-PRF pieces, forming the "dentin block". After that, the sockets will be carefully packed with the dentin block and it will be covered with L-PRF membrane. To ensure stability and prevent displacement, the wounds will be secured using non-resorbable sutures. **Name:** Partially Demineralized Dentin Block **Type:** BIOLOGICAL #### Intervention 2 **Arm Group Labels:** - Xenograft **Description:** In the control group using the Xenograft, the same extraction and socket debridement procedure will be performed. Following that, the extraction socket will be thoroughly filled with deproteinized bovine bone mineral, and a collagen membrane will be employed to cover the socket. The membrane will be shaped to extend 2-3 mm beyond the margins of the extraction socket and positioned just beneath the marginal mucosa. To ensure its stability, a cross-suture will be performed, securing the membrane in place. **Name:** Xenograft **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Description:** CBCT scans will be performed at baseline and 6 months postoperatively. Measurements will be taken at both time points using identical reference points and lines. To establish a reference, the most apical point of the extraction socket will be identified on the baseline image, and two reference lines will be drawn. The vertical reference line will be placed at the midpoint of the extraction socket, intersecting the apical reference point. Additionally, a horizontal reference line will be drawn perpendicular to the vertical line, passing through the apical reference point. The horizontal ridge width will be measured at three specific levels: 1 mm, 3 mm, and 5 mm below the most coronal aspect of the crest. These measurements will be denoted as HW-1, HW-3, and HW-5, respectively. **Measure:** Change in radiographic horizontal ridge width **Time Frame:** at baseline and 6 months postoperatively #### Secondary Outcomes **Description:** CBCT scans will be performed at baseline and 6 months postoperatively. Measurements will be taken at both time points using identical reference points and lines. To establish a reference, the most apical point of the extraction socket will be identified on the baseline image, and two reference lines will be drawn. The vertical reference line will be placed at the midpoint of the extraction socket, intersecting the apical reference point. The height of the alveolus will be measured at the midbuccal aspect (BH) and midlingual aspect (LH). **Measure:** Change in radiographic buccal and palatal ridge height **Time Frame:** at baseline and 6 months postoperatively **Description:** The biopsies will be stored in a 10% formalin solution for preservation. Afterward, they will undergo decalcification in EDTA for a duration of four weeks. Following decalcification, the specimens will be processed and embedded in paraffin to create tissue blocks. Longitudinal sections of 5μm thickness will be cut from the paraffin blocks. These sections will be stained using hematoxylin and eosin (H\&E) or Masson's trichromatic (MT) stains for histological evaluation and histomorphometric analysis. **Measure:** Percentage of new vital bone formation and residual graft **Time Frame:** after 6 months postoperatively **Description:** The primary stability of the implant fixture will be assessed using the Osstell Mentor Resonance Frequency Analyzer (Osstell AB, Goteborg, Sweden). Two measurements will be taken in the buccolingual and mesiodistal directions for each implant. The average of these two measurements will be recorded as the representative implant stability quotient (ISQ) for each individual implant. **Measure:** Implant Primary Stability **Time Frame:** after 6 months postoperatively ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients with non-restorable teeth and Type II extraction socket in the esthetic zone * Healthy patients with adequate oral hygiene (bleeding on probing ≤20%; Plaque index ≤20%). * Systemically healthy. Exclusion Criteria: * Heavy smokers (more than 10 cigarettes per day or an electronic cigarette dose of \>6 mg/ml of nicotine). * Patients reporting systemic conditions that may compromise healing or bone metabolism (eg: diabetes). * Patients with poor oral hygiene (bleeding on probing \>20%; Plaque index \>20%) * The presence of acute periapical infection. * The presence of severe periodontal destruction. **Healthy Volunteers:** True **Maximum Age:** 60 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Danah Al Ghothani, Bachelor **Phone:** 1026826826 **Phone Ext:** +20 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Weam Elbattawy, Ass. Prof **Role:** CONTACT #### Locations **Location 1:** **City:** Cairo **Country:** Egypt **Facility:** Faculty of dentistry Cairo University **State:** Elmanil **Status:** RECRUITING #### Overall Officials **Official 1:** **Affiliation:** Cairo University **Name:** Manal Hosny, Professor **Role:** STUDY_DIRECTOR ## Derived Section ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429527 **Brief Title:** Vision Test App and Questionnaire for 1-Week Post-Cataract Surgery Follow-Up: A Multi-Center Randomized Controlled Trial **Official Title:** Evaluating App-Based Vision Testing (WHOeyes) Combined With the Questionnaire as a Substitute for One-Week Postoperative In-Clinic Follow-Up in Age-Related Cataract Patients: A Multi-center Randomized Controlled Trial #### Organization Study ID Info **ID:** 2024KYPJ037 #### Organization **Class:** OTHER **Full Name:** Zhongshan Ophthalmic Center, Sun Yat-sen University ### Status Module #### Completion Date **Date:** 2024-11 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2024-10 **Type:** ESTIMATED #### Start Date **Date:** 2024-05 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-09 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** West China Hospital **Class:** OTHER **Name:** People's Hospital of Guangxi **Class:** OTHER **Name:** Beijing Tongren Hospital **Class:** OTHER **Name:** Eye & ENT Hospital of Fudan University **Class:** OTHER **Name:** Shanxi Eye Hospital **Class:** OTHER **Name:** Shenzhen Eye Hospital **Class:** OTHER **Name:** The Eye Hospital of Wenzhou Medical University **Class:** OTHER **Name:** The First Affiliated Hospital of Zhengzhou University #### Lead Sponsor **Class:** OTHER **Name:** Zhongshan Ophthalmic Center, Sun Yat-sen University #### Responsible Party **Investigator Affiliation:** Zhongshan Ophthalmic Center, Sun Yat-sen University **Investigator Full Name:** Lixia Luo **Investigator Title:** Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** The goal of this clinical trial is to learn if an app-based vision testing (WHOeyes) combined with a questionnaire can recognize those who have to go back to the hospital, and thus replace the in-clinic 1-week review after an uncomplicated cataract surgery in people with senile cataract. It will also learn about the cost-effectiveness and environmental benefits of such remote follow-up pattern. Besides, the safety and user's satisfaction will also be evaluated. The main questions it aims to answer are: For people with uncomplicated senile cataract, does 1-week clinical follow-up replaced with remote follow-up (using a vision test app and a questionnaire) not adversely affect patients' prognosis? Can this alternative approach bring greater cost-effectiveness and environmental friendliness compared to the traditional follow-up method? Researchers will compare one-week remote follow-up to a routine clinical follow-up to see if one-week remote follow-up is feasible. Participants will: Visit the clinic to finish routine follow-up 1 day and 1 month after cataract surgery. Using app (WHOeyes) and a questionnaire at home or visit the clinic 1 week after cataract surgery. ### Conditions Module **Conditions:** - Cataract Senile **Keywords:** - cataract - telemedicine - health economics - carbon emission - follow-up postoperatively ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 334 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** One week postoperatively, the participants use the WHOeyes app to test their uncorrected visual acuity and fill in a self-made discomfort identification questionnaire. Visit the clinics for review 1 day and 1 month post-cataract surgery. **Intervention Names:** - Behavioral: WHOeyes combined with a questionnaire. **Label:** Remote follow-up **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Participants routinely returned to the hospital for review 1 day, 1 week and 1 month post-cataract surgery **Label:** Usual care **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Remote follow-up **Description:** The WHOeyes app (a self-administered visual acuity testing app) plus a questionnaire (to ask the patients to go to the hospital if they ever experience ocular discomfort including eye redness, discharge, etc.) will be used for 1-week follow-up after cataract surgery, and only those with significant vision loss based on WHOeye test or with ocular discomfort are advised to return to the hospital for follow-up. **Name:** WHOeyes combined with a questionnaire. **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** Using the ETDRS chart to test the BCVA of the operative eye. **Measure:** The best corrected distant visual acuity (BCVA) of the operative eye **Time Frame:** 1 month after cataract surgery #### Secondary Outcomes **Description:** Mean difference in costs divided by mean difference in quality adjusted life years (QALYs). **Measure:** Incremental cost-effectiveness ratios (ICERs) **Time Frame:** 1 month postoperatively **Description:** Collect the carbon emission related activity data generated in the process of postoperative follow-up of patients and hospital through enquiry and questionnaire. **Measure:** Carbon emission **Time Frame:** 1 week and 1 month postoperatively **Description:** Using the ETDRS chart to test the UDVA of the operative eye. **Measure:** Uncorrected distant visual acuity (UDVA)of the operative eye **Time Frame:** 1 month postoperatively **Description:** The proportion of postoperative complications of cataract in the two groups 1 week after surgery was calculated, and the postoperative complications were diagnosed by professional doctors. **Measure:** Incidence and severity of postoperative complications **Time Frame:** Until 1 month postoperatively **Description:** Collected by self-reported outcomes and past medical records (if any) of subjects. **Measure:** Incidence and severity of self-reported ocular discomfort **Time Frame:** Until 1 month postoperatively **Description:** Collected by self-reported outcomes and past medical records (if any) of subjects. **Measure:** Number of unplanned visits **Time Frame:** Until 1 month after cataract surgery **Description:** Vision-specific quality of life is measured by the Chinese version of 9-item short-form of Catquest questionnaire (Catquest-9SF). There are five text response options for the answers scaled from "Yes, very great difficulties" to "No, no difficulties" including answer "Cannot decide". The minimum score is 9 and maximum score is 36, and lower scores mean a better outcome. **Measure:** Patient reported outcome measures (PROMs): Catquest-9SF **Time Frame:** 1 month after cataract surgery **Description:** Vision-specific quality of life as measured by the Chinese version of National Eye Institute Visual Function Questionnaire (NEI-VFQ-25). The minimum score is 0 and maximum score is 100, and higher scores mean a better outcome. **Measure:** Patient reported outcome measures (PROMs): NEI-VFQ-25 **Time Frame:** 1 month after cataract surgery **Description:** Health-related quality of life as measured by the Chinese version of five-level EuroQol five-dimensional questionnaire (EQ-5D-5L). The overall answer for the five dimensions can be combined into a five-digit number that describes the patient's health state. The raw scores are also converted to an EQ-5D index value (Chinese value set) ranging from -0.391 (worst perceived health state) to 1 (best perceived health state). **Measure:** Patient reported outcome measures (PROMs): EQ-5D-5L **Time Frame:** 1 month after cataract surgery **Description:** Assessed by a self-made questionnaire, the answer of it can converted into a 5-point scale. The minimum value is 1 and the maximum value is 5. The higher the scores are, the greater the satisfaction the users have. **Measure:** Users' satisfaction with the WHOeyes app **Time Frame:** 1 month after cataract surgery ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Senile cataract patients undergoing Phaco + IOL implantation for the first time under local anesthesia. 2. Aged between 50 and 80 years old (inclusive), regardless of gender. 3. Possession of a smartphone and capable of understanding and correctly installing and using WHOeyes for visual acuity examination after physician's guidance, . 4. Able to understand and cooperate with the trial procedures, voluntarily participate in this clinical trial, and sign an informed consent form. Exclusion Criteria: 1. Complicated with other serious eye diseases except cataract. 1. History of chronic or recurrent diseases during screening (e.g., keratitis or corneal malnutrition, iritis, scleritis, uveitis, iridocyclitis, excluding refractive errors, dry eye, and chronic conjunctivitis). 2. Presence of ocular infection or active inflammation in either eye during screening. 3. History of acute uveitis within the past 6 months during screening. 4. Intraocular pressure \>21mmHg or a history of glaucoma in the study eye during screening. 5. Presence of unstable active lesions or other ocular diseases judged by the investigator to potentially affect the evaluation of this trial or subject safety, such as moderate to severe diabetic retinopathy, wet age-related macular degeneration, retinal detachment, etc. 6. Congenital abnormalities in the study eye (e.g., congenital cataracts, aniridia). 7. Best corrected visual acuity in the non-operative eye \<0.1. 2. History of ocular trauma in the study eye. 3. History of ocular surgery in the study eye, such as glaucoma surgery, vitrectomy, corneal refractive surgery, corneal transplantation. 4. Planned ocular surgery in either eye during the trial period, such as trabeculectomy, corneal transplantation. 5. Occurrence of complications (e.g., elevated intraocular pressure, corneal edema) within 1 day after cataract surgery. 6. Implantation of a functional intraocular lens (Toric or multifocal intraocular lens). 7. Best corrected visual acuity of the operative eye less than 0.5 within 1 day after surgery. 8. People with severe chronic systemic diseases or who are susceptible to infection. 1. Poorly controlled diabetes (fasting blood sugar \>10 mmol/L) during screening. 2. Poorly controlled hypertension (systolic blood pressure ≥140mmHg, diastolic blood pressure ≥90mmHg) during screening. 3. Require systemic treatment for infectious diseases during screening; 4. With cachexia or bone marrow suppression. 5. History of acquired immunodeficiency syndrome or positive human immunodeficiency virus antibodies during screening. 6. Presence of other severe cardiovascular, pulmonary, hepatic, renal, endocrine, immune, dermatological, musculoskeletal, neurological, or psychiatric diseases, hearing impairment, or mobility impairment, as deemed unsuitable for participation in this trial by the investigator. 9. Participation in other clinical trials within the past month (excluding those who only participated in clinical trial screening without using trial drugs or devices). 10. Pregnant or lactating women. 11. Patients deemed unsuitable for participation in this trial for other reasons by the investigator. **Maximum Age:** 80 Years **Minimum Age:** 50 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007905 - Term: Lens Diseases - ID: D000005128 - Term: Eye Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC11 - Name: Eye Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M5638 - Name: Cataract - Relevance: HIGH - As Found: Cataract - ID: M10917 - Name: Lens Diseases - Relevance: LOW - As Found: Unknown - ID: M8271 - Name: Eye Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002386 - Term: Cataract ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429514 **Brief Title:** Study on the Mechanism of Ganoderma Lucidum Spore Powder in the Treatment of Depression **Official Title:** Based on the Theory of Gut-brain Axis, the Intervention Effect and Related Mechanism of Ganoderma Lucidum Spore Powder on Depressive Symptoms in Patients With Thyroid Cancer Were Investigated #### Organization Study ID Info **ID:** IRB-2023-307 #### Organization **Class:** OTHER **Full Name:** Zhejiang Cancer Hospital ### Status Module #### Completion Date **Date:** 2024-05-03 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2024-05-03 **Type:** ACTUAL #### Start Date **Date:** 2023-03-28 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-15 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Zhejiang Shouxiangu Pharmaceutical Co,. Ltd. #### Lead Sponsor **Class:** OTHER **Name:** Ling Zhiqiang #### Responsible Party **Investigator Affiliation:** Zhejiang Cancer Hospital **Investigator Full Name:** Ling Zhiqiang **Investigator Title:** Principal Investigator **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** To clarify the clinical effect of Ganoderma lucidum spore powder intervention on postoperative depressive symptoms of papillary thyroid carcinoma ; to elucidate the antidepressant mechanism of Ganoderma lucidum spore powder. **Detailed Description:** After being informed of the study and potential risks, all patients who gave written informed consent were enrolled. A total of 300 eligible patients were randomly assigned in a double-blind manner and divided into experimental group and control group at a ratio of 2 : 1. The subjects were given oral test drugs ( Ganoderma lucidum spore powder or placebo ) 4g per day for 90 days from the first day after enrollment. ### Conditions Module **Conditions:** - Depression - Thyroid Cancer **Keywords:** - Depression - Thyroid Cancer - the gut-brain axis - ganoderma lucidum ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Patients with depressive symptoms after papillary thyroid carcinoma surgery 300 cases ; there were 200 cases in the experimental group and 100 cases in the control group. From the first day after enrollment, the subjects were given 4 g of the test drug ( Ganoderma lucidum spore powder or placebo ) every day for 90 days. ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 298 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Oral administration of Ganoderma lucidum spore powder 4g per day ( 1 bag at a time, 2 times a day, 2g / bag ) for 90 days **Intervention Names:** - Dietary Supplement: Ganoderma lucidum spore powder **Label:** Ganoderma lucidum spore powder **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Oral ' placebo ' 4g per day ( 1 bag at a time, 2 times a day, 2g / bag ) for 90 days. **Intervention Names:** - Other: placebo **Label:** placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Ganoderma lucidum spore powder **Description:** One bag at a time, 2 times a day, 2g / bag **Name:** Ganoderma lucidum spore powder **Type:** DIETARY_SUPPLEMENT #### Intervention 2 **Arm Group Labels:** - placebo **Description:** One bag at a time, 2 times a day, 2g / bag **Name:** placebo **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** hamilton depression rating scale relieved from 8-20 to ≤8 **Measure:** Depression symptoms relieved **Time Frame:** Day0,Month3 #### Secondary Outcomes **Description:** The increase of intestinal microbial diversity and abundance **Measure:** Changes of intestinal microbial diversity in patients **Time Frame:** Day0,Month3 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria * patients with depressive symptoms after surgery for papillary thyroid carcinoma in the outpatient department of Zhejiang Cancer Hospital * Han nationality * No previous depression and other mental diseases * 18-80 years old * Women * BMI 19 \~ 24 Exclusion Criteria * suffering from other diseases of the intestinal system * Gastrointestinal surgery was performed before intervention * Including patients with other malignant tumors, who need chemotherapy, radiotherapy, biological therapy or traditional Chinese medicine treatment received antibiotics or microecological modulators within 3 months before the intervention * Acute intestinal obstruction * Patients with severe depressive symptoms who must receive antidepressant treatment organic diseases such as heart and brain diseases, brain trauma history of mental illness, use of psychoactive drugs such as drugs * Severe liver and kidney dysfunction * Pregnancy, lactation **Maximum Age:** 80 Years **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Hangzhou **Country:** China **Facility:** Zhejiang Cancer Hospital **State:** Zhejiang **Zip:** 310022 #### Overall Officials **Official 1:** **Affiliation:** Zhejiang Cancer Hospital **Name:** Jinbiao Shang **Role:** STUDY_DIRECTOR ## Document Section ### Large Document Module #### Large Docs - Date: 2023-03-28 - Filename: Prot_SAP_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: True - Label: Study Protocol and Statistical Analysis Plan - Size: 350832 - Type Abbrev: Prot_SAP - Upload Date: 2024-05-15T03:08 - Date: 2023-03-28 - Filename: ICF_001.pdf - Has ICF: True - Has Protocol: False - Has SAP: False - Label: Informed Consent Form - Size: 194352 - Type Abbrev: ICF - Upload Date: 2024-05-15T03:09 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001526 - Term: Behavioral Symptoms - ID: D000019964 - Term: Mood Disorders - ID: D000001523 - Term: Mental Disorders - ID: D000004700 - Term: Endocrine System Diseases - ID: D000004701 - Term: Endocrine Gland Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000006258 - Term: Head and Neck Neoplasms ### Condition Browse Module - Browse Branches - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC19 - Name: Gland and Hormone Related Diseases ### Condition Browse Module - Browse Leaves - ID: M7061 - Name: Depressive Disorder - Relevance: HIGH - As Found: Depression - ID: M7058 - Name: Depression - Relevance: HIGH - As Found: Depression - ID: M16723 - Name: Thyroid Neoplasms - Relevance: HIGH - As Found: Thyroid Cancer - ID: M16718 - Name: Thyroid Diseases - Relevance: HIGH - As Found: Thyroid - ID: M4818 - Name: Behavioral Symptoms - Relevance: LOW - As Found: Unknown - ID: M21835 - Name: Mood Disorders - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown - ID: M7863 - Name: Endocrine Gland Neoplasms - Relevance: LOW - As Found: Unknown - ID: M9348 - Name: Head and Neck Neoplasms - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000013964 - Term: Thyroid Neoplasms - ID: D000013959 - Term: Thyroid Diseases - ID: D000003863 - Term: Depression - ID: D000003866 - Term: Depressive Disorder ### Intervention Browse Module - Browse Branches - Abbrev: HB - Name: Herbal and Botanical - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: T274 - Name: Reishi - Relevance: HIGH - As Found: ADE ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429501 **Acronym:** LAFF **Brief Title:** Local Anesthesia for Facial Fractures **Official Title:** The Impact of Perioperative Nerve Block on Opioid Use After Craniomaxillofacial Trauma Surgery: A Randomized Controlled Trial #### Organization Study ID Info **ID:** 202401085 #### Organization **Class:** OTHER **Full Name:** Washington University School of Medicine ### Status Module #### Completion Date **Date:** 2025-07-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2025-07-01 **Type:** ESTIMATED #### Start Date **Date:** 2024-04-02 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-04-23 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Washington University School of Medicine #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Is US Export:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** The study is a double-blind randomized, placebo controlled trial examining the impact of perioperative bupivacaine nerve block on PACU recovery metrics. Patients with operative facial fractures are randomized to receive either bupivacaine or saline injections prior to the anesthesia emergence. **Detailed Description:** Effective pain management is critical to successful postoperative care and is known to decrease patient morbidity, incurred patient and hospital costs, and length of hospital stay. Pain and nausea after surgery for traumatic facial fractures can limit patients' early morbidity, oral intake, and ability to communicate. The study is a double-blind randomized, placebo controlled trial examining the impact of perioperative bupivacaine nerve block on PACU recovery metrics. Patients with operative mandibular or midface fractures are randomized to receive either bupivacaine or saline injections prior to the anesthesia emergence. The primary outcome measure is the amount of opioid that patients receive in PACU in morphine milligram equivalent (MMEs). The purpose of the study is to define whether a perioperative bupivacaine nerve block results in a decrease in the amounts of opioids and antiemetics that patients receive in PACU after CMF trauma surgery. ### Conditions Module **Conditions:** - Pain Management **Keywords:** - otolaryngology - surgery - facial plastic - trauma ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Double-blinded, placebo-controlled randomized clinical trial ##### Masking Info **Masking:** QUADRUPLE **Masking Description:** All study team members and the participants will be blinded to the assignment of participants in the study groups. Only the pharmacist will prepare the study syringes and the unblinded statistician will have access to the study group assignments. **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 70 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The surgeon will be provided with a 10 mL syringe, and he/she will be blinded to the contents of the syringe. The appropriate landmarks will be identified, and a 21, 25, or 27- gauge needle will be used to perform the nerve block with 0.25% bupivacaine. **Intervention Names:** - Drug: Bupivacaine/Epinephrine **Label:** Bupivacaine injection **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** The placebo sham injection will be performed in an identical fashion as the nerve block with the exception of using 10 mL of 0.9% saline injection instead of bupivacaine. **Intervention Names:** - Drug: Saline **Label:** Saline injection **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Bupivacaine injection **Description:** injection **Name:** Bupivacaine/Epinephrine **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Saline injection **Description:** injection **Name:** Saline **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** To evaluate the impact of a perioperative bupivacaine nerve block on PACU opioid use in patients undergoing operative fixation of facial fractures compared to placebo nerve block assessment of the amount of opioids that patients receive in PACU in morphine milligram equivalents (MMEs) will be calculated. **Measure:** Impact of a perioperative bupivacaine nerve block on PACU opioid use as assessed by the amount of opioids received in morphine milligram equivalents (MMEs). **Time Frame:** day 1 or the day of surgery #### Secondary Outcomes **Description:** To evaluate the impact of a perioperative bupivacaine nerve block on PACU antiemetic use in patients undergoing operative fixation of facial fractures compared to placebo nerve block. Additional variables that will be collected perioperatively include the medications used for induction/maintenance of anesthesia as well as intraoperative analgesia (I.e. fentanyl, hydromorphone, morphine, acetaminophen, ketorolac, etc.), operative time, estimated blood loss, and intraoperative complications. **Measure:** Impact of a perioperative bupivacaine nerve block on antiemetic use as assessed by the numbers who receive opioids and antiemetics, amount of antiemetics, pain score, frequency of emesis, and time until discharge. **Time Frame:** within 1 month post surgery ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Adults age 18 and over 2. Isolated facial fracture to the mandible and/or midface undergoing surgical repair 3. No allergy to local anesthetic 4. Ability to read, write, and understand English Exclusion Criteria: 1. Patients under the age of 18 2. Isolated nasal bone fracture 3. Polytrauma (I.e. injury pattern resulting in hospital admission for multiple bony fractures outside of the face) 4. Allergy to local anesthetic **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Amrita Hari-Raj, MD **Phone:** 314-518-6410 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Sara Kukuljan **Phone:** 314-362-7563 **Role:** CONTACT #### Locations **Location 1:** **City:** Saint Louis **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Sara Kukuljan - **Phone:** 314-362-7563 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Amrita Hari-Raj, MD - **Phone:** 314-518-6410 - **Role:** CONTACT **Country:** United States **Facility:** Washington University **State:** Missouri **Status:** RECRUITING **Zip:** 63110 #### Overall Officials **Official 1:** **Affiliation:** Washington University School of Medicine **Name:** Amrita Hari_Raj, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Washington University School of Medicine **Name:** Jay Piccirillo, MD **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Hedegaard H, Minino AM, Spencer MR, Warner M. Drug Overdose Deaths in the United States, 1999-2020. NCHS Data Brief. 2021 Dec;(426):1-8. **PMID:** 34978529 **Citation:** Abraham AJ, Rieckmann T, Gu Y, Lind BK. Inappropriate Opioid Prescribing in Oregon's Coordinated Care Organizations. J Addict Med. 2020 Jul/Aug;14(4):293-299. doi: 10.1097/ADM.0000000000000569. **PMID:** 31609864 **Citation:** BJC Healthcare. Level I Trauma Center. Barnes-Jewish Hospital. https://www.barnesjewish.org/Medical-Services/Trauma-Acute-CareSurgery/Level-I-Trauma-Center **Citation:** Lapidus JB, Santosa KB, Skolnick GB, Som A, Cho GJ, Waljee JF, AuBuchon JD, Patel KB. Opioid Prescribing and Use Patterns in Postsurgical Facial Trauma Patients. Plast Reconstr Surg. 2020 Mar;145(3):780-789. doi: 10.1097/PRS.0000000000006588. **PMID:** 32097326 **Citation:** Perloff MD, Chung JS. Urgent care peripheral nerve blocks for refractory trigeminal neuralgia. Am J Emerg Med. 2018 Nov;36(11):2058-2060. doi: 10.1016/j.ajem.2018.08.019. Epub 2018 Aug 8. **PMID:** 30119988 **Citation:** Staity G, Saadi RA, Pool C, Lighthall JG. The Safety Profile of Liposomal Bupivacaine Use in Septorhinoplasty. Facial Plast Surg Aesthet Med. 2022 May-Jun;24(3):202-206. doi: 10.1089/fpsam.2020.0544. Epub 2021 Feb 22. **PMID:** 33617355 **Citation:** Schumacher JK, Cristel RT, Talugula S, Shah AR. The Use of Adjunctive Perioperative Nerve Blocks in Rhinoplasty in the Immediate Postoperative Period. Facial Plast Surg Aesthet Med. 2023 Jul-Aug;25(4):361-362. doi: 10.1089/fpsam.2022.0125. Epub 2022 Sep 14. No abstract available. **PMID:** 36106969 **Citation:** The University of Iowa Otolaryngology Protocols. https://medicine.uiowa.edu/iowaprotocols/maximum-recommended-doses-andduration-local-anesthetics **Citation:** Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007 May;39(2):175-91. doi: 10.3758/bf03193146. **PMID:** 17695343 ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown - ID: M26370 - Name: Fractures, Bone - Relevance: LOW - As Found: Unknown - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M21089 - Name: Facies - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Ancestors - ID: D000000779 - Term: Anesthetics, Local - ID: D000000777 - Term: Anesthetics - ID: D000002492 - Term: Central Nervous System Depressants - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000018689 - Term: Sensory System Agents - ID: D000018373 - Term: Peripheral Nervous System Agents - ID: D000000316 - Term: Adrenergic alpha-Agonists - ID: D000000322 - Term: Adrenergic Agonists - ID: D000018663 - Term: Adrenergic Agents - ID: D000018377 - Term: Neurotransmitter Agents - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000318 - Term: Adrenergic beta-Agonists - ID: D000001993 - Term: Bronchodilator Agents - ID: D000001337 - Term: Autonomic Agents - ID: D000018927 - Term: Anti-Asthmatic Agents - ID: D000019141 - Term: Respiratory System Agents - ID: D000009184 - Term: Mydriatics - ID: D000013566 - Term: Sympathomimetics - ID: D000014662 - Term: Vasoconstrictor Agents ### Intervention Browse Module - Browse Branches - Abbrev: VaCoAg - Name: Vasoconstrictor Agents - Abbrev: Resp - Name: Respiratory System Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: Analg - Name: Analgesics ### Intervention Browse Module - Browse Leaves - ID: M7992 - Name: Epinephrine - Relevance: HIGH - As Found: Less - ID: M4107 - Name: Anesthetics - Relevance: LOW - As Found: Unknown - ID: M5315 - Name: Bupivacaine - Relevance: HIGH - As Found: Following - ID: M4033 - Name: Analgesics, Opioid - Relevance: LOW - As Found: Unknown - ID: M30371 - Name: Racepinephrine - Relevance: LOW - As Found: Unknown - ID: M211043 - Name: Epinephryl borate - Relevance: LOW - As Found: Unknown - ID: M4109 - Name: Anesthetics, Local - Relevance: LOW - As Found: Unknown - ID: M20746 - Name: Adrenergic Agents - Relevance: LOW - As Found: Unknown - ID: M3668 - Name: Adrenergic alpha-Agonists - Relevance: LOW - As Found: Unknown - ID: M3673 - Name: Adrenergic Agonists - Relevance: LOW - As Found: Unknown - ID: M20504 - Name: Neurotransmitter Agents - Relevance: LOW - As Found: Unknown - ID: M3670 - Name: Adrenergic beta-Agonists - Relevance: LOW - As Found: Unknown - ID: M5269 - Name: Bronchodilator Agents - Relevance: LOW - As Found: Unknown - ID: M20963 - Name: Anti-Asthmatic Agents - Relevance: LOW - As Found: Unknown - ID: M21137 - Name: Respiratory System Agents - Relevance: LOW - As Found: Unknown - ID: M12139 - Name: Mydriatics - Relevance: LOW - As Found: Unknown - ID: M16345 - Name: Sympathomimetics - Relevance: LOW - As Found: Unknown - ID: M17409 - Name: Vasoconstrictor Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000004837 - Term: Epinephrine - ID: D000002045 - Term: Bupivacaine ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429488 **Brief Title:** Obsessive-compulsive Disorder, Depression and Anxiety Among Patients With Crohn's Disease **Official Title:** Obsessive-compulsive Disorder, Depression and Anxiety Among Patients With Crohn's Disease #### Organization Study ID Info **ID:** 233/2022 #### Organization **Class:** OTHER **Full Name:** University of Jordan ### Status Module #### Completion Date **Date:** 2023-09-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-31 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-29 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2023-03-01 **Type:** ACTUAL #### Start Date **Date:** 2022-09-01 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-17 **Study First Submit QC Date:** 2024-05-23 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of Jordan #### Responsible Party **Investigator Affiliation:** University of Jordan **Investigator Full Name:** Mohammad Sami El Muhtaseb **Investigator Title:** Associate Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Introduction: Crohn's disease (CD) and obsessive-compulsive disorder (OCD) are two distinct medical conditions that affect millions of people worldwide. While numerous studies have explored anxiety and depression in CD, there is a notable lack of research about the link between OCD and CD. The aim of the study is to look for a relation between these seemingly unrelated conditions. Methods: Patients with a diagnosis of Crohn's disease were given four different questionnaires in order to assess for the presence of obsessive-compulsive disorder, depression, and anxiety symptoms using the OCI-R score, DASS-21, PHQ-9, and GAD-7. The same questionnaires were used to assess healthy controls for similar symptoms. **Detailed Description:** This is an observational case-control study conducted at Jordan University Hospital. Using hospital medical records, patients with Crohn's disease who had been treated and followed up at the gastro-enterology and colorectal clinics were contacted to obtain consent to participate in the research and to explain its goals and the nature of the questionnaires used. Patients who agreed to participate were sent an online questionnaire to fill in. Healthy Controls with no medical illness or mental illness were invited to fill in the same questionnaire. The controls were relatives of patients attending the hospital for clinics not related to the gastrointestinal tract or psychiatry. Patients and controls with documented psychiatric illnesses were excluded. The following psychological assessment tools were used: The Obsessive-Compulsive Inventory-Revised (OCI-R) for obsessive-compulsive symptoms. It is composed of an 18-item self-report validated questionnaire that measures symptoms across 6 subscales including washing, checking, neutralizing, obsessing, ordering, and hoarding. The possible range of scores is 0-72. The Depression Anxiety Stress Scales-21 (DASS-21) for overall emotional well-being. It is a set of three self-report scales to understand the degree of stress and distress, depressive and anxiety symptoms. The shortened version was used, which consists of 21 items and has been widely used for research and clinical purposes and is easy to administer. The Patient Health Questionnaire-9 (PHQ-9), a nine-item depression scale of the patient health questionnaire, to assess depressive symptoms. The individual responses are interpreted as a score, with depression divided from no depression to severe depression. The Generalized Anxiety Disorder-7 (GAD-7), a seven-item tool used to measure or assess anxiety symptoms and the severity of generalized anxiety disorder (GAD). Data analysis: The data was collected using Microsoft Forms and downloaded into Excel for coding and deidentification before being imported into the Statistical Package for Social Science (IBM SPSS Statistics for Windows, version 25, IBM Corp., Armonk, N.Y., USA) for analysis. The chi-square test was used to compare different categorical variables. The Mann-Whitney U test was used to compare non-categorical variables. The Kruskal-Wallis test was applied to test for significant differences between the scales. Ethical consideration: This study adhered to the principles of the Declaration of Helsinki 1975 and was approved by the Institutional Review Board at Jordan University Hospital. ### Conditions Module **Conditions:** - Inflammatory Bowel Diseases ### Design Module #### Design Info **Observational Model:** CASE_CONTROL **Time Perspective:** CROSS_SECTIONAL #### Enrollment Info **Count:** 293 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** patients diagnosed with CD at the department of Gastroenterology were collected from hospital records, and all patients were contacted and accepted to be part of this study **Intervention Names:** - Other: no intervention, questionnaires were used **Label:** chron's disease patients #### Arm Group 2 **Description:** Healthy Controls with no medical illness or mental illness before were invited to fill in the same questionnaire, the controls were relatives of patients attending the hospital for clinics not related to the gastrointestinal tract or psychiatry **Intervention Names:** - Other: no intervention, questionnaires were used **Label:** Healthy controls ### Interventions #### Intervention 1 **Arm Group Labels:** - Healthy controls - chron's disease patients **Description:** The following psychological assessment tools were used: Obsessive-Compulsive Inventory-Revised (OCI-R): An 18-item self-report questionnaire measuring symptoms across six subscales: washing, checking, neutralizing, obsessing, ordering, and hoarding. A score of 21 or higher indicates likely OCD. Depression Anxiety Stress Scales-21 (DASS-21): A set of three self-report scales assessing stress, depression, and anxiety over 21 items. This shortened version is widely used for research and clinical purposes and is easy to administer. Patient Health Questionnaire-9 (PHQ-9): A nine-item scale for assessing depressive symptoms. Scores are categorized as: 1-4 (no/minimal), 5-9 (mild), 10-14 (moderate), 15-19 (moderately severe), and 20-27 (severe depression). Generalized Anxiety Disorder-7 (GAD-7): A seven-item tool measuring anxiety symptoms and the severity of generalized anxiety disorder (GAD). **Name:** no intervention, questionnaires were used **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** The Depression Anxiety Stress Scales-21 (DASS-21) **Measure:** This study aims to determine the prevalence of obsessive-compulsive disorder in patients with CD and compare it with people without CD (controls) **Time Frame:** 6 months #### Secondary Outcomes **Description:** The Patient Health Questionnaire-9 (PHQ-9) **Measure:** This study aims to determine the Patient Health Questionnaire-9 (PHQ-9) in patients with CD and compare it with people without CD (controls) **Time Frame:** 6 months **Description:** The Generalized Anxiety Disorder-7 (GAD-7) **Measure:** This study aims to determine the Generalized Anxiety Disorder-7 (GAD-7) in patients with CD and compare it with people without CD (controls) **Time Frame:** 6 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients diagnosed with Crohn's disease who have been treated and followed up at the gastro-enterology and colorectal clinics of Jordan University Hospital. * Patients who have provided informed consent to participate in the research after being informed about the study's goals and the nature of the questionnaires used. * Healthy controls with no prior history of medical or mental illness. * Controls who are relatives of patients attending non-gastroenterology and non-psychiatry clinics at Jordan University Hospital. * Participants (both patients and healthy controls) who agree to fill in the online questionnaire. Exclusion Criteria: - Patients and controls with documented psychiatric illnesses. **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** This is an observational case-control study was conducted at Jordan University Hospital, Using hospital medical records, patients with Crohn's disease who been treated and followed up at the gastro-enterology and colorectal clinics were contacted to obtain their consent to participate in the research and to explain its goals and the nature of the questionnaires used. Patients who agreed to participate were sent an online questionnaire to fill in. Healthy Controls with no medical illness or mental illness before were invited to fill in the same questionnaire, the controls where relatives of patients attending the hospital for clinics not related to the gastrointestinal tract or psychiatry. Patients and controls with documented psychiatric illnesses were excluded. ### Contacts Locations Module #### Locations **Location 1:** **City:** Amman **Country:** Jordan **Facility:** the Jordan University Hospital **Zip:** 11942 ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000005759 - Term: Gastroenteritis - ID: D000005767 - Term: Gastrointestinal Diseases - ID: D000004066 - Term: Digestive System Diseases - ID: D000007410 - Term: Intestinal Diseases - ID: D000010554 - Term: Personality Disorders - ID: D000001523 - Term: Mental Disorders - ID: D000001008 - Term: Anxiety Disorders ### Condition Browse Module - Browse Branches - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions - Abbrev: BC06 - Name: Digestive System Diseases ### Condition Browse Module - Browse Leaves - ID: M7061 - Name: Depressive Disorder - Relevance: LOW - As Found: Unknown - ID: M7058 - Name: Depression - Relevance: LOW - As Found: Unknown - ID: M6638 - Name: Crohn Disease - Relevance: HIGH - As Found: Crohn's Disease - ID: M6419 - Name: Compulsive Personality Disorder - Relevance: HIGH - As Found: Compulsive Disorder - ID: M12706 - Name: Obsessive-Compulsive Disorder - Relevance: HIGH - As Found: Obsessive-Compulsive Disorder - ID: M4324 - Name: Anxiety Disorders - Relevance: LOW - As Found: Unknown - ID: M10444 - Name: Intestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M17917 - Name: Inflammatory Bowel Diseases - Relevance: HIGH - As Found: Inflammatory Bowel Disease - ID: M13462 - Name: Personality Disorders - Relevance: LOW - As Found: Unknown - ID: M8875 - Name: Gastroenteritis - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003424 - Term: Crohn Disease - ID: D000015212 - Term: Inflammatory Bowel Diseases - ID: D000003193 - Term: Compulsive Personality Disorder - ID: D000009771 - Term: Obsessive-Compulsive Disorder ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429475 **Acronym:** AIRSA001 **Brief Title:** Anti-Inflammatory Reliever South Africa **Official Title:** Anti-Inflammatory Reliever Therapy for Asthma Using Inhaled Budesonide/Formoterol As-needed With or Without Maintenance in South African Children: A Pragmatic Open Label Phase 3 Randomised Controlled Trial #### Organization Study ID Info **ID:** BREC/00005663/2023 #### Organization **Class:** OTHER **Full Name:** University of KwaZulu ### Status Module #### Completion Date **Date:** 2026-05-28 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2025-05-28 **Type:** ESTIMATED #### Start Date **Date:** 2024-05-25 **Type:** ESTIMATED **Status Verified Date:** 2024-03 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-04-08 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of KwaZulu #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Is US Export:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** This is a Phase 3 single-centre open label randomised controlled trial with two equal sized groups to assess the efficacy of budesonide/formoterol 80/4.5 (6-11 years) and 160/4.5 (12-18 years) compared to the standard of care in reducing asthma exacerbations over 52 weeks. Children and adolescents with a diagnosis of asthma or newly diagnosed with asthma will be screened for eligibility for enrolment. Those who had an asthma exacerbation in the previous year will be randomised 1:1, to either receive budesonide/formoterol inhaler for both symptom relief and for chronic anti- inflammatory maintenance therapy or the standard of care which is separate inhalers for symptom relief (short acting bronchodilator salbutamol) and chronic maintenance therapy with inhaled corticosteroids (beclomethasone or budesonide) and/or long-acting beta agonists or montelukast as determined by treating physicians. All asthma exacerbations and clinic/hospital admissions will be recorded for the duration of the 52-week follow-up. Participants will be followed up at 13, 26, 39 and 52 weeks. The 13- and 39-week visit will be telephonic visits to capture the primary end-point i.e. asthma exacerbations. Adverse events and medication changes data will also be collected. An independent Data and Safety Monitoring Board (DSMB) will be convened for this study with expertise in asthma and asthma clinical trials. The purpose of the DSMB will be to monitor the study for safety and operational futility with pre-defined stopping criteria. In addition, a Trial Steering Committee (TSC) will also provide overall supervision of the trial and ensure the trial is delivered in accordance with ICH-GCP. The TSC has been established with an independent Chair and include additional independent members including an observer early career researcher. Representatives of the Trial Funder (NIHR) and Sponsor (AHRI) will be invited to all TSC meetings. **Detailed Description:** Over the last two decades non-communicable diseases (NCDs) have been rising in sub-Saharan Africa, and NCDs are set to overtake communicable, maternal, neonatal, and nutritional diseases combined as the leading cause of mortality in sub-Saharan Africa by 2030. Many NCDs have their roots in childhood with lifestyle changes in combination with an increasing median population age in Africa making a further dramatic rise in NCDs in Africa's near future highly likely. The World Health Organization (WHO) now considers the prevention and control of NCDs as an urgent development issue and essential to the achievement of the Sustainable Development Goals (SDG) and this can only be achieved with childhood interventions. The 2018 WHO report on NCDs, reported 3.8 million deaths annually from non-communicable respiratory diseases (asthma and chronic obstructive pulmonary disease), with 78% of deaths in low-income and middle-income countries (LMICs). Asthma morbidity and mortality are preventable with inhaled therapies-however, there is lack of evidence on how to deliver these in an affordable and effective way. The WHO highlights asthma as an under-appreciated cause of poverty in LMICs that retards economic and social development, erodes the health and well-being of those affected and has a negative impact on families and societies. Asthma aggravates poverty and poverty aggravates asthma. Children miss out on education, adults lose days at work and the costs of drugs, emergency visits, and hospitalization are major financial burdens, not only for individuals/families but also for struggling health systems. In South Africa, asthma is the most common NCD in childhood affecting 1 in 5 children with a prevalence of asthma symptoms at 21% in adolescence. Despite the availability of asthma medicines in the Essential Medicines List, asthmatic children report having severe asthma symptoms in over 50% of those with asthma. South Africa still reports the fourth highest mortality rate globally. The core to asthma management includes use of chronic use of anti-inflammatory inhaled corticosteroids to address the inflammatory process in the airways (maintenance) and bronchodilators (relievers) for relief of the bronchospasm. Many studies have shown that asthma mortality is linked to poor use of anti-inflammatory inhaler treatment and over-reliance on short- acting β2 bronchodilator reliever therapy to treat asthma exacerbations. In many LMICs including South Africa, the use of controller treatment use of anti-inflammatory inhalers is limited, with only 40% of people with severe asthma symptoms using regular ICS for chronic asthma treatment, but with over 89% using their short-acting β2 agonists. There is a large body of evidence showing that overuse of SABAs is linked with asthma mortality and poorer outcomes. The combination treatment with budesonide/formoterol for the management of asthma has transformed asthma treatment in high-income countries (HIC), where it is recommended in the very first step of asthma treatment as both an anti-inflammatory and reliever therapy. With the "as needed" use of budesonide/formoterol, asthmatics benefit from the additional dose of a maintenance anti-inflammatory dose, which improves symptom control and reduces exacerbations. This approach has not been adopted in many LMICs related to access to budesonide/formoterol and its cost and therefore, people in LMICs are relegated to use of Track 2 of Global Initiative of Asthma (GINA) treatment which still suggests the use of separate anti-inflammatory and reliever inhalers. To address this gap, a large body of randomized controlled clinical trial evidence (SYGMA, Novel START, PRACTICAL, and several trials of SMART), have shown that use of budesonide/formoterol as needed (for exacerbations) and for long-term controller treatment compared to separate inhaled corticosteroid and short-acting bronchodilators, reduces the number of asthma exacerbations and improves quality of life. The trials have though been limited in that there is no data on the cost-effectiveness of this approach in lower resourced settings and limited data from small studies participant numbers (\<100) of this approach in children 6-11 years of age. Based on this, the approach of using budesonide/formoterol has not been recommended by the Global Initiative of Asthma (GINA) strategy for global asthma management in Step 1 and 2 of treatment in children 6-11 years of age both in HIC and LMICs, but rather on the higher steps of asthma treatment where symptoms are more severe. The investigators therefore propose in a randomized controlled trial to assess the efficacy of budesonide/formoterol compared to the standard of care (separate inhaled corticosteroid and bronchodilator) inhaler approach to prevent asthma exacerbations, improve asthma control and quality of life and to also assess the cost-effectiveness of budesonide/formoterol compared to standard of care in children and adolescents in South Africa. The data will be novel as the investigators will for the first time include a large number of children in a clinical trial comparing the two approaches, to provide definitive evidence of the efficacy and cost-effectiveness of this approach in children and adolescents. ### Conditions Module **Conditions:** - Asthma **Keywords:** - asthma - budesonide/formoterol - beclomethasone - budesonide - children - adolescents ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Randomised Clinical Trial ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 1038 **Type:** ESTIMATED **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Budesonide-formoterol fumarate dihydrate at two dose strengths 80/4.5 and 160/4.5 administered via a pressurized metered dose inhaler (pMDI) or dry powder inhaler (DPI), respectively. The dosing will be dependent on asthma symptom severity ranging from 1 dose as needed and titrated up or down depending on asthma control. **Intervention Names:** - Drug: Budesonide/formoterol **Label:** budesonide/formoterol group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Standard of care **Intervention Names:** - Drug: standard of care **Label:** comparator: standard of care group **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - budesonide/formoterol group **Description:** The Investigational Medicinal Product (IMP) consists of a combination of Budesonide (corticosteroid) and Formoterol Furamate (fast-acting β2 agonist) dihydrate. The IMP is currently available and registered in dry powder form turbuhaler (Symbicort) and a pressurised metered dose inhaler (Vannair). The recommended doses are pMDI/DPI 80/4.5 1-2 puffs twice daily OR 1 puff as needed (a maximum daily dose of 8 puffs) for children 6-11 years of age and 160/4.5 1-2 inhalations twice daily or 1 puff as needed (a maximum daily dose of 12 puffs) for adolescents 12-18 years. **Name:** Budesonide/formoterol **Other Names:** - No other intervention names **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - comparator: standard of care group **Description:** Any therapy that is prescribed as per asthma guidelines i.e. beclomethasone, budesonide and salbutamol, montelukast etc **Name:** standard of care **Other Names:** - beclomethasone or budesonide & salbutamol or mentelukast **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Questionnaire- based-tool to capture number of exacerbations will be administered biweekly via a short message system, 6 monthly telephonic consultations and alternative 6 monthly clinic visits. Unscheduled visits will be captured using the bi-weekly questionnaires. **Measure:** Number of exacerbations in 52 weeks ( End of study) **Time Frame:** 52 weeks #### Secondary Outcomes **Description:** Cost effectiveness will assessed using health economics , health facility and quality of life questionnaires that will be administered to the participants, caregivers and facility managers. **Measure:** Cost effectiveness **Time Frame:** 52 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Age for inclusion children and adolescents 6-18 years at the time of consent * Known asthmatic on treatment. * Newly diagnosed asthma based on investigator review and/or medical report. * All patients will have their asthma diagnosis confirmed (both new or known asthmatic patients) by either spirometry with reversibility or excessive diurnal variability by PEFR twice daily over 2 weeks. * Ability to perform Peak Expiratory Flow rate and/or bronchodilator reversibility testing. * Only participants with mild, or moderate asthma , based on medical history * At least one exacerbation of asthma in the past year as defined by an event requiring treatment with systemic corticosteroids for ≥3 days and/or a hospitalisation/emergency room visit for asthma requiring treatment with systemic corticosteroids. * Written consent from the participant or parent/guardian and assent from study participants where applicable. * Participant and/or parent/guardian agrees to comply with the study procedures, including the completion of the visits and be available for contact for telephonically for the non-contact visits Exclusion Criteria: * Tuberculosis (TB): active TB disease and contact with people with active TB disease in the last 6 months. * Chronic sputum expectoration, chest pain, shortness of breath, dizziness, or light-headedness in the last 2 months. * Cardiac arrythmia. * Chronic conditions: thyrotoxicosis, phaeochromocytoma, cardiovascular disease, severe hypertension. * Uncontrolled diabetes mellitus * Patients with Peak Expiratory Flow Rate \< 50% of predicted , as these would be classified as severe asthmatics. * Patients with any history of life-threatening asthma, defined as any history of significant asthma episode(s) requiring intubation associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma related syncopal episode(s). * Any use of biological therapy or immunomodulatory therapy such as methotrexate or regular oral prednisolone for the asthma management (STEP 5 GINA therapy). * Any surgical or medical condition that would significantly alter the absorption, distribution, metabolism or excretion of the IMP which may jeopardise the safety of the participants. The investigator should make this determination in consideration of the volunteer's medical history. * Any physical, mental or social condition, laboratory abnormality of history of illness that in the investigator's judgement might jeopardise the safety of the participant in the context of the study or might interfere with study procedures or the ability of the participant to adhere to and complete the study. The investigator should make this determination consideration of the volunteer's medical history. * Inability to present for follow-up or leaving the study area within 12 months of enrolment. **Maximum Age:** 18 Years **Minimum Age:** 6 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Refiloe Masekela, PhD **Phone:** +27794890936 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Nompumelelo Ngobese **Phone:** +27352510925 **Role:** CONTACT #### Overall Officials **Official 1:** **Affiliation:** Africa Health Research Institute **Name:** Limakatso Lebina, PhD **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **Description:** A log of names, signatures and initials of all staff authorized or delegation to enter data into a participant's clinic file and eCRF will be kept. The Investigator will maintain paper or electronic source documentation for all study participants. Protocol-specific participant information will be captured in an eCRF. All records will be kept in a secure storage area password protected electronic source, with limited access. Clinical information will not be released without the written permission of the participant, except as necessary for monitoring, and auditing by the Regulatory Authority or the Institutional Review Board (IRB)/ BREC. **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001982 - Term: Bronchial Diseases - ID: D000012140 - Term: Respiratory Tract Diseases - ID: D000008173 - Term: Lung Diseases, Obstructive - ID: D000008171 - Term: Lung Diseases - ID: D000012130 - Term: Respiratory Hypersensitivity - ID: D000006969 - Term: Hypersensitivity, Immediate - ID: D000006967 - Term: Hypersensitivity - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC20 - Name: Immune System Diseases ### Condition Browse Module - Browse Leaves - ID: M27137 - Name: Respiratory Aspiration - Relevance: LOW - As Found: Unknown - ID: M4556 - Name: Asthma - Relevance: HIGH - As Found: Asthma - ID: M5258 - Name: Bronchial Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M11170 - Name: Lung Diseases, Obstructive - Relevance: LOW - As Found: Unknown - ID: M10018 - Name: Hypersensitivity - Relevance: LOW - As Found: Unknown - ID: M14967 - Name: Respiratory Hypersensitivity - Relevance: LOW - As Found: Unknown - ID: M10020 - Name: Hypersensitivity, Immediate - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001249 - Term: Asthma ### Intervention Browse Module - Ancestors - ID: D000000893 - Term: Anti-Inflammatory Agents - ID: D000001993 - Term: Bronchodilator Agents - ID: D000001337 - Term: Autonomic Agents - ID: D000018373 - Term: Peripheral Nervous System Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000018927 - Term: Anti-Asthmatic Agents - ID: D000019141 - Term: Respiratory System Agents - ID: D000005938 - Term: Glucocorticoids - ID: D000006728 - Term: Hormones - ID: D000006730 - Term: Hormones, Hormone Substitutes, and Hormone Antagonists - ID: D000058666 - Term: Adrenergic beta-2 Receptor Agonists - ID: D000000318 - Term: Adrenergic beta-Agonists - ID: D000000322 - Term: Adrenergic Agonists - ID: D000018663 - Term: Adrenergic Agents - ID: D000018377 - Term: Neurotransmitter Agents - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: Infl - Name: Anti-Inflammatory Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Repr - Name: Reproductive Control Agents - Abbrev: Resp - Name: Respiratory System Agents ### Intervention Browse Module - Browse Leaves - ID: M4217 - Name: Anti-Inflammatory Agents - Relevance: LOW - As Found: Unknown - ID: M3767 - Name: Albuterol - Relevance: LOW - As Found: Unknown - ID: M21711 - Name: Budesonide - Relevance: HIGH - As Found: Metabolic - ID: M4800 - Name: Beclomethasone - Relevance: HIGH - As Found: Mirror - ID: M304 - Name: Formoterol Fumarate - Relevance: HIGH - As Found: Anesthetic - ID: M274108 - Name: Montelukast - Relevance: LOW - As Found: Unknown - ID: M5269 - Name: Bronchodilator Agents - Relevance: LOW - As Found: Unknown - ID: M20963 - Name: Anti-Asthmatic Agents - Relevance: LOW - As Found: Unknown - ID: M21137 - Name: Respiratory System Agents - Relevance: LOW - As Found: Unknown - ID: M9047 - Name: Glucocorticoids - Relevance: LOW - As Found: Unknown - ID: M9789 - Name: Hormones - Relevance: LOW - As Found: Unknown - ID: M9788 - Name: Hormone Antagonists - Relevance: LOW - As Found: Unknown - ID: M20746 - Name: Adrenergic Agents - Relevance: LOW - As Found: Unknown - ID: M3670 - Name: Adrenergic beta-Agonists - Relevance: LOW - As Found: Unknown - ID: M3673 - Name: Adrenergic Agonists - Relevance: LOW - As Found: Unknown - ID: M20504 - Name: Neurotransmitter Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000019819 - Term: Budesonide - ID: D000001507 - Term: Beclomethasone - ID: D000068759 - Term: Formoterol Fumarate ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429462 **Acronym:** K4L **Brief Title:** Knee4Life Project: Empowering Knee Recovery After Total Knee Replacement Through Digital Health **Official Title:** Empowering Knee Recovery After Total Knee Replacement Through Digital Health (Knee4life Project) #### Organization Study ID Info **ID:** 339937 #### Organization **Class:** OTHER **Full Name:** University of Exeter ### Status Module #### Completion Date **Date:** 2025-05 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2025-05 **Type:** ESTIMATED #### Start Date **Date:** 2024-05-01 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-02 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER_GOV **Name:** National Institute for Health Research, United Kingdom **Class:** UNKNOWN **Name:** Exeter Biomedical Research Centre (BRC) grant #### Lead Sponsor **Class:** OTHER **Name:** University of Exeter #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The research project will investigate the extent to which a smartphone camera sensor tool can help predict and measure knee stiffness and pain after Total Knee Replacement Surgery (TKR) and how a tool such as this could be implemented into the NHS. Total knee replacement (TKR) is a frequent procedure undertaken in England and Wales, with more than 100,000 conducted each year. Although most patients have a successful outcome following their TKR, approximately 10-20% of patients are dissatisfied, predominantly because of pain and knee stiffness. A method to detect early problems with pain and stiffness could facilitate earlier referral to non-surgical treatments, which are effective in preventing the need for manipulation under anaesthetic (MUA). Here the investigators will validate and provide proof of concept for a smartphone camera sensor tool that measures knee range of motion alongside symptoms of pain for use in the home setting. The study will comprise of 3 stages; 1. We will conduct 45 minute online interviews comprising of (1) people who have had total knee replacement surgery, (2) healthcare professionals and stakeholders. 2. We will invite 30 participants who are 5-9 weeks post TKR and 30 participants who have had no previous musculoskeletal injuries to attend a session at the university. The lab testing will be conducted at the VSimulator, a biomechanics research lab at the Exeter Science park, and at the teaching labs on St Lukes Campus, Exeter. Here participants be asked to answer 8 questionnaires and have some of their movements measured. 3. Participants will be asked to repeat the 'timed up and go' and the 'sit to stand' tests in their homes and record them using a mobile device. The study is funded by the NIHR Exeter Biomedical Research Centre grant and sponsored by the University of Exeter. **Detailed Description:** 1. Background Total knee replacement (TKR) is a common procedure, with more than 100,000 per year undertaken in England and Wales. Although most patients have a successful outcome following their TKR, approximately 10-20% of patients are dissatisfied, chiefly because of pain and knee stiffness. A method to detect early problems with pain and stiffness could facilitate earlier referral to non-surgical treatments, which are effective in preventing the need for manipulation under anaesthetic \[MUA\]. Currently, rates of MUA are 2.5% (\~2,500 patients per year in England and Wales), costing \~£14k per procedure. Our current understanding of when stiffness develops and the timing and best treatment(s) for stiffness are limited. A recent James Lind Alliance Priority Setting Partnership identified stiffness after TKR as a top-10 research priority to better understand and test interventions. Current measures are not accurate or suitable for use in the home. The investigators need tools to accurately measure early indicators for stiffness. 2. Rationale The investigators currently have no tool to remotely and accurately detect development of early post-surgical knee stiffness. This study aims to develop a cost-effective tool to measure and quantify knee stiffness before and after total knee replacement (TKR) surgery for use across the NHS. The research seeks to understand how knee range of motion (ROM) recovers after TKR and detect early signs of stiffness. It also aims to predict who might develop stiffness after TKR and explore the relationship between pain and stiffness. Current methods for measuring knee range of motion (ROM), such as hand-held tools for measuring angles, have limitations in terms of accuracy and need trained healthcare staff to use them. The ideal tool would be low-cost, easy to use, and provide rapid feedback to patients and clinical teams. The study will involve the development and validation of a computer vision-based approach (using cameras to assess movements) to monitor knee flexion and extension, and a walking pattern assessment. Video-based technology or computer vision (CV) has recently been pioneered in Exeter to measure spine movement in patients with ankylosing spondylitis. Computer vision is an emerging technology that has great potential for monitoring knee flexion in people with knee stiffness. This approach involves the use of cameras and machine learning algorithms to detect and analyse knee joint angles during movement automatically. By providing objective and accurate measurements of knee flexion, computer vision has the potential to improve the assessment of knee stiffness and facilitate targeted treatment interventions. However, as with any new technology, there is a need to validate the method in the context of patients with knee stiffness to ensure its accuracy and reliability. Studies have highlighted the importance of developing machine learning algorithms specifically for this patient population to account for individual differences in movement patterns and limitations due to stiffness. Further research is needed to assess the validity and feasibility of computer vision-based approaches for monitoring knee flexion in people with knee stiffness, which could ultimately improve the diagnosis, monitoring, and management of this condition. Validation of the computer vision-based approach for monitoring knee flexion in people with knee stiffness is essential to ensure its reliability and accuracy. This requires developing and refining machine learning algorithms that can accurately detect and measure knee joint angles in this patient population. This study will evaluate the accuracy and precision of the algorithm against gold-standard measurement methods, such as motion capture or goniometry. Furthermore, this study will examine the sensitivity of the approach to changes in knee flexion due to stiffness and pain and assess its feasibility in a clinical setting. Once validated, the computer vision-based approach has the potential to provide a non-invasive and objective means of monitoring knee flexion in people with knee stiffness, which could inform treatment decisions and improve patient outcomes. Another tool which the investigators will use is the Gaitcapture app which takes advantage of the accelerometer and gyroscope sensor in a mobile phone and acts similarly to an inertial measurement unit (IMU) to provide us with acceleration and rotation data. The validation of the computer vision-based approach will involve comparing it against gold-standard measurement methods (specialist physiotherapy assessment). In addition to the computer vision-based approach, the study will utilise body-worn sensors and mobile apps to monitor the physical activity levels, walking patterns and step counts of participants. This data will provide insights into people with TKR's overall physical activity patterns and help evaluate the usability, acceptability, feasibility, and accuracy of the tools for diagnostics and monitoring. The findings of this research project have the potential to improve the diagnosis, monitoring, and management of knee stiffness after total knee replacement (TKR), with the potential to reducing the need for MUA surgery. By providing accurate measurements and early detection, the tools developed in this study could enable earlier referral to non-surgical treatments and reduce the need for costly and risky procedures to improve knee range of motion (ROM) after total knee replacement (TKR) surgery, like a manipulation of the knee under anaesthesia. Here, the investigators will conduct a validation study of a marker-less motion capture algorithm to determine its accuracy and assess its feasibility and usability for implementation on a large scale in the home. the investigators will also ascertain the test-retest reliability of algorithm outputs such as knee flexion/extension angles. ### Conditions Module **Conditions:** - Total Knee Replacement **Keywords:** - rehabilitation - surgery - motion capture - focus group ### Design Module #### Design Info **Observational Model:** CASE_CONTROL **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 75 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants will be asked to complete 8 questionnaires before the lab assessments: The data will be entered and saved onto REDCap by a member of the research team. The 8 questionnaires including baseline data are PROMIS-29 v2, Oxford Knee Score, IPAQ Short Last 7 Days, Numeric Rating Scale, Single Ease Question, Barthel Index for Activities of Daily Living and EQ-5D-5L. Participants will be asked to complete the following: 2-minute walk on a treadmill 10 m walk (5 m x 2). Timed up and Go (TUG) Sit to stand test At home: TUG Sit to stand test **Intervention Names:** - Diagnostic Test: smartphone camera sensor tool **Label:** Healthy Controls (lab assessment) #### Arm Group 2 **Description:** Participants will be asked to complete 8 questionnaires before the lab assessments: The data will be entered and saved onto REDCap by a member of the research team. The 8 questionnaires including baseline data are PROMIS-29 v2, Oxford Knee Score, IPAQ Short Last 7 Days, Numeric Rating Scale, Single Ease Question, Barthel Index for Activities of Daily Living and EQ-5D-5L. Participants will be asked to complete the following: 2-minute walk on a treadmill 10 m walk (5 m x 2). Timed up and Go (TUG) Sit to stand test At home: TUG Sit to stand test **Intervention Names:** - Diagnostic Test: smartphone camera sensor tool **Label:** Participant post total knee replacement surgery (lab assessment) #### Arm Group 3 **Description:** A member of the research team will conduct interviews to discuss how the knee4life project and how final tool can be deployed in clinics and services. These discussions will provide valuable insights into the future adoption and application of computer-vision technology. These will take place online. **Label:** Healthcare professionals (focus group) #### Arm Group 4 **Description:** A member of the research team will conduct interviews to discuss how the knee4life project and how final tool can be deployed in clinics and services. These discussions will provide valuable insights into the future adoption and application of computer-vision technology. These will take place online. **Label:** Stakeholders (focus group) #### Arm Group 5 **Description:** A member of the research team will conduct interviews to discuss how the knee4life project and how final tool can be deployed in clinics and services. These discussions will provide valuable insights into the future adoption and application of computer-vision technology. These will take place online. **Label:** Participants post total knee replacement surgery ### Interventions #### Intervention 1 **Arm Group Labels:** - Healthy Controls (lab assessment) - Participant post total knee replacement surgery (lab assessment) **Description:** The study will involve the development and validation of a computer vision-based approach (using cameras to assess movements) to monitor knee flexion and extension, and a walking pattern assessment. **Name:** smartphone camera sensor tool **Type:** DIAGNOSTIC_TEST ### Outcomes Module #### Primary Outcomes **Description:** To validate in the lab and provide proof of concept for a smartphone camera sensor tool that measures knee range of motion (ROM) alongside symptoms of pain for use in the home setting. This will be assessed by comparing the knee joint angles and range of motion measures using two different forms of motion capture during different movements. **Measure:** Validation of the accuracy and reliability of camera sensor tool through comparison of knee joint angles based on motion capture from different sources **Time Frame:** through study completion, an average of 1 year **Description:** To investigate who might develop stiffness after Total Knee Replacement surgery. This will be measured by looking at the range of motion of the knee using motion capture data. **Measure:** Predicting knee stiffness after surgery through analysis of knee joint angles **Time Frame:** through study completion, an average of 1 year **Description:** Participants will be questioned on how painful their knee is post surgery using the Oxford pain score questionnaire. **Measure:** Knee pain measured through the oxford pain score questionnaire **Time Frame:** through study completion, an average of 1 year #### Secondary Outcomes **Description:** Through feedback from focus groups and assessment of accuracy and reliability, the camera sensor tool will be tested to see whether it could be considered a tool that would be used in clinical settings. **Measure:** Feasibility of clinical integration of camera sensor tool **Time Frame:** through study completion, an average of 1 year ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * People aged ≥18 years old * Recently had a total knee replacement surgery or has worked with people following this surgery as a clinical, carer or therapist * Able to give informed consent * Able to communicate in English with the research team Exclusion Criteria: * Any medical condition compromising the safety or the ability to take part in the study * Unable to adhere to study procedures **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Convenience sampling will be used to recruit healthcare professionals and stakeholders. Participants need to be identified within the timeline and scope of the project. Obtaining volunteers who are easily available and willing is a sensible sampling strategy for the scope of the project. They will be identified through professional networks and associations and will be invited to take part in the study by the University of Exeter research team via email. Participants post-TKR will be recruited using a purposive sampling method, where individuals are selected based on their unique characteristics or experiences. For instance, they will be identified through hospital records and invited to participate by the NHS trust research team. ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Maedeh Mansoubi, PhD **Phone:** 07866138722 **Role:** CONTACT #### Locations **Location 1:** **City:** Exeter **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Maedeh Mansoubi - **Phone:** 07427164717 - **Role:** CONTACT **Country:** United Kingdom **Facility:** University of Exeter **Status:** RECRUITING **Zip:** EX1 2LP ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429449 **Brief Title:** Mitoxantrone for Venetoclax Resistant Acute Myeloid Leukemia **Official Title:** Mitoxantrone for Venetoclax Resistant Acute Myeloid Leukemia #### Organization Study ID Info **ID:** 24-0178.cc #### Organization **Class:** OTHER **Full Name:** University of Colorado, Denver ### Status Module #### Completion Date **Date:** 2027-11 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2026-12 **Type:** ESTIMATED #### Start Date **Date:** 2024-12 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-13 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of Colorado, Denver #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Is US Export:** True **Oversight Has DMC:** True ### Description Module **Brief Summary:** This is an open label, phase 1 study for AML subjects with relapsed or refractory disease or subjects in morphologic remission with MRD+ after first line therapy with venetoclax+HMA. A preliminary dose-finding cohort will be followed by 3 expansion cohorts. **Detailed Description:** This is an open label, phase 1 study for AML subjects with relapsed or refractory disease or subjects in morphologic remission with MRD+ after first line therapy with venetoclax+HMA. A preliminary dose-finding cohort will be followed by 3 expansion cohorts. Cohort 1 will be a conventional 3+3 dose-escalation study to determine maximum tolerated (MTD) or recommended dose of mitoxantrone when used with venetoclax+azacitidine. Subjects who are refractory to first-line therapy with venetoclax+HMA, or who respond and then relapse after first line therapy with venetoclax+HMA, will enroll in the study and receive a subsequent cycle of venetoclax+azacitidine at the dose and schedule being administered per the standard of care, along with a starting dose of 4mg/m2 of mitoxantrone administered IV on days 1-4. Depending on the absence or frequency of dose-limiting toxicities, additional patients will be enrolled at the appropriate dose levels, increasing by 2mg/m2 per cycle, per the 3+3 design until the MTD or a dose of 10mg/m2 of mitoxantrone is reached. The dose escalation phase will conclude when the MTD is determined; if the MTD is not reached, a recommendation for a dose of mitoxantrone in combination with venetoclax+azacitidine will be made based on toxicity and efficacy data. After the establishment of the MTD or recommended dose of mitoxantrone, an expansion cohort (cohort 2) will open. 10 subjects who are refractory to first-line therapy with venetoclax+HMA, or who respond and then relapse after first line therapy with venetoclax+HMA, will enroll in the study and receive a subsequent cycle of venetoclax+azacitidine at the dose and schedule being administered per the standard of care, with the determined MTD/recommended dose of IV mitoxantrone given on days 1-4. On day 28 +/- 7 days of this cycle, a bone marrow biopsy will be repeated. In the absence of a ≥50% blast reduction from baseline, the subject will discontinue the study. If a CR, CRi, MLFS or blast reduction from baseline of ≥50% occurs, the subject can continue sequential cycles of venetoclax+azacitidine at the dose and schedule being administered per the standard of care, with the MTD/recommended dose of mitoxantrone on days 1-4, for up to 3 total cycles. No subject will receive \>3 cycles of mitoxantrone. After mitoxantrone cycles have been completed, subjects will receive a bone marrow biopsy after the third cycle, and then continue bone marrow biopsies with MRD assessments every 6 months, until disease progression or the administration of any therapy other than venetoclax+azacitidine, at which time the subject will be discontinued from the study. In cohort 3, subjects who are in a morphologic remission with MRD+ after ≤3 cycles of standard of care venetoclax+HMA will enroll and receive mitoxantrone on days 1-4 at a dose to-be-determined that is below the MTD from cohort 1, concurrently with venetoclax+azacitidine, at the dose and schedule being administered per the standard of care, over a 28-day treatment cycle. A bone marrow biopsy with MRD assessment will be performed on day 28 +/- 7 days. If MRD conversion to negative occurs, subsequent treatment cycles will continue to administer venetoclax+azacitidine, at the dose and schedule being administered per the standard of care, with the to-be-determined dose of mitoxantrone on days 1-4, for a maximum of three total cycles of mitoxantrone. If MRD conversion to negative does not occur, the next cycle may escalate the mitoxantrone dose to a level to-be-determined and not exceeding the MTD, with venetoclax+azacitidine at the dose and schedule being administered per the standard of care. If MRD conversion to negative occurs, subsequent treatment cycles will continue to administer venetoclax+azacitidine, at the dose and schedule being administered per the standard of care, with the to-be-determined dose of IV mitoxantrone on days 1-4, for a maximum of three total cycles of mitoxantrone. If MRD conversion to negative does not occur, the next cycle may escalate the mitoxantrone to a level to-be-determined and not exceeding the MTD, with venetoclax+azacitidine at the dose and schedule being administered per the standard of care. Subjects will not receive \>3 cycles of mitoxantrone. After mitoxantrone cycles have been completed, subjects will continue bone marrow biopsies with MRD assessments every 6 months, until disease progression or the administration of any therapy other than venetoclax+azacitidine, at which time the subject will be discontinued from the study. In cohort 4, subjects who are in a morphologic remission with MRD+ after \>3 cycles of standard of care venetoclax/HMA will enroll 28-50 days after the start of the previous venetoclax/HMA cycle. They will receive mitoxantrone IV on days 1-4 at a dose to-be-determined that is below the MTD from cohort 1; on day 14, the subject will start venetoclax+azacitidine at the dose and schedule being administered per the standard of care. On day 42 +/- 7 days, a bone marrow biopsy, with MRD assessment, will be repeated. If MRD conversion to negative occurs, subsequent treatment cycles will continue to administer venetoclax+azacitidine, at the dose and schedule being administered per the standard of care, with the to-be-determined dose of IV mitoxantrone on days 1-4, for a maximum of three total cycles of mitoxantrone. If MRD conversion to negative does not occur, the next cycle will retain the same schedule, and may escalate the mitoxantrone to a dose level to-be-determined and not exceeding the MTD. If MRD conversion to negative occurs, one additional cycle of mitoxantrone at this dose, with venetoclax+azacitidine at the dose and schedule being administered per the standard of care, will be given. If MRD conversion to negative does not occur, the next cycle will retain the same schedule, and may escalate the mitoxantrone to a level to-be-determined and not exceeding the MTD. No subject will receive \>3 cycles of mitoxantrone. After mitoxantrone cycles have been completed, subjects will continue bone marrow biopsies with MRD assessments every 6 months, until disease progression or the administration of any therapy other than venetoclax+azacitidine, at which time the subject will be discontinued from the study. ### Conditions Module **Conditions:** - Leukemia - Myeloid Leukemia - Monocytic Leukemia ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** SEQUENTIAL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 30 **Type:** ESTIMATED **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Cohort 1 will be a conventional 3+3 dose-escalation study to determine maximum tolerated (MTD) or recommended dose of mitoxantrone when used with venetoclax+azacitidine. **Intervention Names:** - Drug: Venetoclax - Drug: Azacitidine - Drug: Mitoxantrone **Label:** Cohort 1 **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** After establishing the MTD of mitoxantrone, an expansion cohort will open. 10 subjects refractory to first-line therapy w/venetoclax+HMA, or respond then relapse after first-line therapy w/venetoclax+HMA, will enroll in the study \& receive a subsequent cycle of venetoclax+azacitidine at the dose \& schedule being administered per the standard of care, w/the determined MTD/recommended dose of IV mitoxantrone given days 1-4. Day 28 +/- 7 days of this cycle, a bone marrow biopsy will be repeated. In the absence of a ≥50% blast reduction from baseline, the subject will discontinue the study. If a CR, CRi, MLFS or blast reduction from baseline of ≥50% occurs, the subject can continue sequential cycles of venetoclax+azacitidine at the dose \& schedule being administered per the standard of care, with the MTD/recommended dose of mitoxantrone on days 1-4, up to 3 cycles. No subject will receive \>3 cycles of mitoxantrone. **Intervention Names:** - Drug: Venetoclax - Drug: Azacitidine - Drug: Mitoxantrone **Label:** Cohort 2 **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Subjects in a morph remission w/ MRD+ after ≤3 cycles of soc ven+HMA will enroll \& receive mitox on days 1-4 at dose tbd that is below the MTD from cohort 1, concurrently w/ven+aza, at the dose \& schedule being soc admin, over a 28-day cycle. A BMBX w/ MRD assessment will be done day 28. If MRD- occurs, subseq treatment cycles will continue to admin ven+aza, at the dose \& schedule being soc admin, w/ the tbd dose of mitox on days 1-4, for max of 3 cycles. If MRD- does not occur, the next cycle may escalate the mitox dose to a level tbd \& not exceeding the MTD, w/ ven+aza at the dose \& schedule being soc admin. If MRD- occurs, subseq treatment cycles will continue to admin ven+aza, at the dose \& schedule being soc admin, with the tbd dose of IV mitox on days 1-4, for a max of 3 cycles. If MRD- does not occur, the next cycle may escalate the mitox to a level tbd \& not exceeding the MTD, w/ ven+aza at the dose \& schedule being admin per the soc. Subjects will not receive \>3 cycles. **Intervention Names:** - Drug: Venetoclax - Drug: Azacitidine - Drug: Mitoxantrone **Label:** Cohort 3 **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** Subjects in a morphologic remission w/ MRD+ after \>3 cyc of soc ven/HMA will enroll 28-50 days after the previous ven/HMA cyc. Subjects will receive mitox IV days 1-4 at a dose tbd below the MTD from cohort 1; on day 14, the subject will start ven+aza at the dose \& schedule per the soc. On day 42, a BMBX, w/ MRD assessment, will be repeated. If MRD- occurs, subseq cyc will cont to admin ven+aza, at the dose \& schedule per the soc, with the tbd dose of IV mitox on days 1-4, for a max of 3 cyc of mitox. If MRD- does not occur, the next cyc will retain the same schedule \& may escalate the mitox to a dose level tbd \& not exceeding the MTD. If MRD- occurs, 1 add'l cyc of mitox at this dose, w/ ven+aza at the dose \& schedule per the soc, will be given. If MRD- does not occur, the next cyc will retain the same schedule \& may escalate the mitox to a level tbd \& not exceeding the MTD. **Intervention Names:** - Drug: Venetoclax - Drug: Azacitidine - Drug: Mitoxantrone **Label:** Cohort 4 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Cohort 1 - Cohort 2 - Cohort 3 - Cohort 4 **Description:** Venetoclax attaches to a protein called Bcl-2. This protein is present in high amounts in CLL cancer cells, where it helps the cells survive for longer in the body and makes them resistant to cancer medicines. By attaching to Bcl-2 and blocking its actions, venetoclax causes the death of cancer cells and thereby slows down progression of the disease. **Name:** Venetoclax **Other Names:** - Venclexta - Venclyxto **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Cohort 1 - Cohort 2 - Cohort 3 - Cohort 4 **Description:** An analog of the pyrimidine nucleoside cytidine, has effects on cell differentiation, gene expression, and deoxyribonucleic acid (DNA) synthesis and metabolism, and causes cytotoxicity. **Name:** Azacitidine **Other Names:** - Onureg - Vidaza **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Cohort 1 - Cohort 2 - Cohort 3 - Cohort 4 **Description:** Mitoxantrone Injection, USP (concentrate) is a synthetic antineoplastic anthracenedione for intravenous use. **Name:** Mitoxantrone **Other Names:** - Novantrone **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Determine the maximum tolerated (MTD) and/or recommended phase 2 dose (RP2D) of mitoxantrone in combination with venetoclax+azacitidine. **Measure:** Maximum tolerated dose (MTD) **Time Frame:** Reassessment at end of each cycle (28 days) until MTD reached, up to 5 cycles total if needed **Description:** Overall response rate (CR+CRi+PR+MLFS) after treatment with mitoxantrone and venetoclax+azacitidine venetoclax+HMA in subjects who have failed first line therapy with this regimen **Measure:** Overall response rate **Time Frame:** Baseline to End of Treatment **Description:** Determine the safety of mitoxantrone in combination or in sequence with standard of care venetoclax+azacitidine **Measure:** Number of grade 4 or 5 adverse events **Time Frame:** Baseline to End of Treatment #### Secondary Outcomes **Description:** Relapse free survival, remission duration, overall survival and adverse events by grade and attribution **Measure:** Survival data **Time Frame:** Through study completion, up to 5 years **Description:** Determine the rate of conversion from MRD+ to MRD- after treatment with mitoxantrone **Measure:** Number of conversions from MRD+ to MRD- **Time Frame:** After each cycle of treatment (28 days), up to 3 cycles total ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Subject must have confirmation of non-APL AML by WHO criteria and have been treated with first-line venetoclax/HMA (azacitidine or decitabine). 2. Subject must have relapsed disease per IWG criteria or disease refractory to first line venetoclax/HMA defined by less than a PR response after ≥ 1 complete cycle of venetoclax/HMA. 3. Subject must have either measurable residual disease (MRD+), as measured by FDA-approved flow cytometric test performed by Hematologics (cohort 3 and 4) or relapsed/refractory disease (cohort 1 and 2). 4. Subject must have a projected life expectancy of at least 12 weeks. 5. Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance status of ≤ 2. 6. Subject must have adequate renal function as demonstrated by a calculated creatinine clearance ≥ 60 mL/min, calculated using the formula CKD-EPI Creatinine Equation 7. Subject must have adequate heart function as measured by left ventricular ejection fraction (LVEF) \>50%, assessed by multigated acquisition (MUGA) or echocardiogram (ECHO) within 1 month prior to study day 1 8. Subject must have adequate liver function as demonstrated by: 1. aspartate aminotransferase (AST) ≤ 3.0 × ULN\* 2. alanine aminotransferase (ALT) ≤ 3.0 × ULN\* 3. bilirubin ≤ 1.5 × ULN, unless due to Gilbert's syndrome\* * Unless considered due to leukemic organ involvement 9. Non-sterile male subjects must use contraceptive methods with partner(s) at least prior to beginning study drug administration and continuing up to 90 days after the last dose of study drug. No contraception is required if male subjects are surgically sterile (vasectomy with medical assessment confirming surgical success) or if the male subject has a female partner who is postmenopausal or permanently sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy). 10. Female subjects must be either: 1. Postmenopausal; defined as Age \> 60 years with no menses for 12 or more months without an alternative medical cause; OR 2. Permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy); OR 3. If subject is of childbearing potential, use of contraception is required while on study treatment and for 6 months after the last dose. 11. Subject must voluntarily sign and date an informed consent, approved by an Institutional Review Board (IRB), prior to the initiation of any research directed procedures. Exclusion Criteria: 1. Subject has known active CNS involvement from AML. 2. Subject has any history of clinically significant condition(s) that in the opinion of the investigator would adversely affect his/her participating in this study including, but not limited to: 1. Significant active cardiac disease within the previous 6 months including: New York Heart Association heart failure \> class 2, unstable angina, or myocardial infarction. 2. Renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or bleeding disorder independent of leukemia. 3. Subject has a malabsorption syndrome or other condition that precludes enteral route of administration. This includes history of inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis), celiac disease (e.g. sprue), prior gastrectomy or upper bowel removal, or any other gastrointestinal disorder or defect that would interfere with the absorption, distribution, metabolism or excretion of the study drug and/or predispose the subject to an increased risk of gastrointestinal toxicity. 4. Subject exhibits evidence of uncontrolled systemic infection requiring therapy (viral, bacterial or fungal). Uncontrolled is defined as ongoing signs/symptoms related the infection without improvement despite appropriate antibiotics, antiviral therapy and/or other treatment. 5. Subject has a history of other malignancies prior to study entry, with the exception of: 1. Adequately treated in situ carcinoma of the breast or cervix uteri 2. Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin 3. Prostate cancer not requiring therapy beyond hormonal therapy 4. Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent 6. Subject has a white blood cell count \> 25 × 109/L. Note: hydroxyurea or apheresis are permitted to meet this criterion (cohort 3 only). 7. Pregnant or breast-feeding females. 8. Known or suspected hypersensitivity to azacitidine or mannitol. 9. Any prior exposure to an anthracycline or anthracenedione **Maximum Age:** 80 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Derek Schatz **Phone:** 720-848-0628 **Role:** CONTACT #### Locations **Location 1:** **City:** Aurora **Country:** United States **Facility:** University of Colorado Hospital **State:** Colorado **Zip:** 80045 #### Overall Officials **Official 1:** **Affiliation:** University of Colorado, Denver **Name:** Andrew Kent, MD, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000006402 - Term: Hematologic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10945 - Name: Leukemia - Relevance: HIGH - As Found: Leukemia - ID: M10955 - Name: Leukemia, Myeloid - Relevance: HIGH - As Found: Myeloid Leukemia - ID: M18127 - Name: Leukemia, Myeloid, Acute - Relevance: HIGH - As Found: Acute Myeloid Leukemia - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M9490 - Name: Hematologic Diseases - Relevance: LOW - As Found: Unknown - ID: T3995 - Name: Myeloid Leukemia - Relevance: HIGH - As Found: Myeloid Leukemia - ID: T182 - Name: Acute Myeloid Leukemia - Relevance: HIGH - As Found: Acute Myeloid Leukemia - ID: T188 - Name: Acute Non Lymphoblastic Leukemia - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007938 - Term: Leukemia - ID: D000007951 - Term: Leukemia, Myeloid - ID: D000015470 - Term: Leukemia, Myeloid, Acute ### Intervention Browse Module - Ancestors - ID: D000000964 - Term: Antimetabolites, Antineoplastic - ID: D000000963 - Term: Antimetabolites - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000970 - Term: Antineoplastic Agents - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000000700 - Term: Analgesics - ID: D000018689 - Term: Sensory System Agents - ID: D000018373 - Term: Peripheral Nervous System Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000059005 - Term: Topoisomerase II Inhibitors - ID: D000059003 - Term: Topoisomerase Inhibitors ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Analg - Name: Analgesics ### Intervention Browse Module - Browse Leaves - ID: M249656 - Name: Venetoclax - Relevance: HIGH - As Found: 15 minutes - ID: M11908 - Name: Mitoxantrone - Relevance: HIGH - As Found: CT scan - ID: M4673 - Name: Azacitidine - Relevance: HIGH - As Found: Frequency - ID: M4281 - Name: Antimetabolites - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: M4032 - Name: Analgesics - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000001374 - Term: Azacitidine - ID: C000579720 - Term: Venetoclax - ID: D000008942 - Term: Mitoxantrone ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429436 **Brief Title:** Vending Machine Naloxone Distribution for Your Community (VENDY) **Official Title:** Vending Machine Naloxone Distribution for Your Community (VENDY): Increasing Reach and Implementation of Naloxone Distribution #### Organization Study ID Info **ID:** 22-0546 #### Organization **Class:** OTHER **Full Name:** University of Colorado, Denver ### Status Module #### Completion Date **Date:** 2026-01-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2025-06-01 **Type:** ESTIMATED #### Start Date **Date:** 2024-06-01 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-10 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** Southern Colorado Harm Reduction Association **Class:** OTHER **Name:** Denver Health and Hospital Authority **Class:** UNKNOWN **Name:** Summit County Public Health Department #### Lead Sponsor **Class:** OTHER **Name:** University of Colorado, Denver #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Is US Export:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Vending machines are an innovative strategy shown to increase access to naloxone, a medication used to reverse opioid overdose. The aim of this proposal is to study the reach of a community-initiated, stakeholder engaged adaptation of naloxone distribution, VEnding machine Naloxone Distribution for Your community (VENDY) program. **Detailed Description:** This pilot assessment of the VENDY program will take place in 3 communities. Each community will have a machine (vending or kiosks) in which naloxone will be distributed for free to community members. Our preliminary work identified the locations desired by community members who use illegal drugs for machine placement. The pilot test test will include evaluation of the reach (naloxone distribution), adoption (% of sites and staff implementing), and implementation (fidelity to restocking and maintenance protocol) of VENDY in each community. ### Conditions Module **Conditions:** - Harm Reduction - Naloxone - Opioid Overdose ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP **Intervention Model Description:** We will be using an interrupted time series design to evaluate naloxone distribution before and after vending machine implementation in each community. ##### Masking Info **Masking:** NONE **Masking Description:** There will be no masking. **Primary Purpose:** HEALTH_SERVICES_RESEARCH #### Enrollment Info **Count:** 1489 **Type:** ESTIMATED **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Each participating site will install at least 1 machine (vending or kiosks) in the respective community for naloxone distribution. **Intervention Names:** - Behavioral: VENDY **Label:** VENDY **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - VENDY **Description:** At least 1 machine (vending machine like a snack machine or a machine like a newspaper kiosk) will be placed in the respective community served by the participating organizations. Any person in the community can get naloxone from the machine. The vending machine will require a code that will be placed on the machine for anyone to use. The kiosks are a box that you simply pull open and naloxone can be obtained. Naloxone kits will be provided for free as part of the current naloxone distribution program within each respective organization. **Name:** VENDY **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** Reach will be assessed using monthly counts of naloxone distribution in the 6 months before and after VENDY implementation. Naloxone counts will include distribution from all sources within the organization and captured through pharmacy fills from the electronic health record and distribution tracking logs. Naloxone machine distribution will be added to the total monthly count in the post implementation phase and obtained using the vending machine electronic software (reporting date and time of distribution) or (for kiosks) the staff monthly refill tracking log capturing quantity of naloxone kits required to fill the machine (captured at least monthly). **Measure:** Reach **Time Frame:** the 6 months pre VENDY implementation and the 6 months post VENDY implementation #### Secondary Outcomes **Description:** Adoption is the percentage of sites placing a naloxone vending machine in the respective community that is made available for community members to obtain naloxone. **Measure:** Adoption **Time Frame:** At the end of program development (program development is the first phase in which each site is developing VENDY over a 6-18 month period of time) **Description:** The count of fatal opioid overdose events for each respective county in which the participating organization and vending machine reside in the year before and year after VENDY implementation. Overdose will be captured from publicly available data from death records reported by the Colorado Department of Public Health and Environment. To address temporality we will include fatal opioid overdose deaths in a comparison community matching community features (urban/rural status, community population, and opioid death rate). **Measure:** Fatal Opioid Overdose Events-Effectiveness **Time Frame:** pre-implementation in the year prior to a live VENDY program and post implementation in the year following live VENDY program **Description:** Fidelity is the percentage of time staff refill and maintain the machine per protocol as measured by the vending machine software and machine activity tracking log. **Measure:** Fidelity-Implementation **Time Frame:** the 6 months following VENDY implementation **Description:** Number of months each organization implementing VENDY continues to make naloxone available in the machines for the 6 months following the initial implementation phase (6 months). **Measure:** Maintenance **Time Frame:** the 6 months following the initial implementation phase (6 months) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Any person in the community who desires to obtain naloxone will be able to use the machines Exclusion Criteria: * Inability to enter a code on a vending machine or open a kiosk. **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Nicole Wagner, PhD **Phone:** (303)724-7095 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Meagan R Bean, MPH **Phone:** (303)724-7095 **Role:** CONTACT ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000062787 - Term: Drug Overdose - ID: D000063487 - Term: Prescription Drug Misuse - ID: D000076064 - Term: Drug Misuse - ID: D000019966 - Term: Substance-Related Disorders - ID: D000064419 - Term: Chemically-Induced Disorders - ID: D000001523 - Term: Mental Disorders - ID: D000009293 - Term: Opioid-Related Disorders - ID: D000079524 - Term: Narcotic-Related Disorders ### Condition Browse Module - Browse Branches - Abbrev: BC25 - Name: Substance Related Disorders - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M2423 - Name: Opiate Overdose - Relevance: HIGH - As Found: Opioid Overdose - ID: M30011 - Name: Drug Overdose - Relevance: LOW - As Found: Unknown - ID: M1557 - Name: Drug Misuse - Relevance: LOW - As Found: Unknown - ID: M30133 - Name: Prescription Drug Misuse - Relevance: LOW - As Found: Unknown - ID: M21837 - Name: Substance-Related Disorders - Relevance: LOW - As Found: Unknown - ID: M30302 - Name: Chemically-Induced Disorders - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown - ID: M12244 - Name: Opioid-Related Disorders - Relevance: LOW - As Found: Unknown - ID: M2057 - Name: Narcotic-Related Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000083682 - Term: Opiate Overdose ### Intervention Browse Module - Browse Branches - Abbrev: NarcAntag - Name: Narcotic Antagonists - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M12221 - Name: Naloxone - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429423 **Brief Title:** Effects of Acute Physical Activity in Patients With Exhaustion Disorder **Official Title:** Acute Psychological and Physiological Exercise Effects Among Patients With Stress-related Exhaustion Disorder. Role of Exercise Intensity. #### Organization Study ID Info **ID:** 2022-04943-01 #### Organization **Class:** OTHER **Full Name:** The Swedish School of Sport and Health Sciences ### Status Module #### Completion Date **Date:** 2024-01-04 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-31 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-30 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2024-01-04 **Type:** ACTUAL #### Start Date **Date:** 2023-02-21 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-02-06 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** Avonova Health AB **Class:** UNKNOWN **Name:** Jenny Kling, Doctoral student, licensed psychologist, The Swedish School of Sport and Health Sciences #### Lead Sponsor **Class:** OTHER **Name:** Victoria Blom #### Responsible Party **Investigator Affiliation:** The Swedish School of Sport and Health Sciences **Investigator Full Name:** Victoria Blom **Investigator Title:** Associate professor in psychology, head of department Institution for physical activity and health, licensed psychologist **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** A new stress-related diagnosis, Exhaustion disorder (ED), was introduced in the Swedish version of ICD-10 in 2005 and has since then increased rapidly. The condition is long-lasting and debilitating, characterized by considerable and persistent fatigue, insomnia, and impaired cognitive function. The diagnosis is still relatively unexplored and there is no consistent knowledge of, among other things, which interventions that work. Research indicates that physical activity can have positive effects on depression, anxiety, and stress. However, there is little knowledge today about the relationship between the dose of physical activity and stress-related illness. It is also not clear how physical activity can be used in the treatment of stress-related illness. The purpose of this project is to gain increased knowledge about the immediate physiological and psychological effects of physical activity for people with diagnosed ED. The project will investigate the psychological and physiological effects of two different intensities of physical activity in people with ED compared to healthy controls. The information from the study also aims to provide a basis for a second part of the project where treatment including physical activity is carried out with people with ED, in a randomized controlled design. **Detailed Description:** Background A new stress-related diagnosis, exhaustion disorder (ED), was introduced in the Swedish version of ICD-10 in 2005, and has since then increased rapidly. The condition is long-lasting and debilitating, characterized by considerable and persistent fatigue, insomnia and impaired cognitive function. The diagnosis is still relatively unexplored and there is no consistent knowledge of, among other things, which interventions that work. There is extensive research on the association between mental health and physical activity in general and exercise specifically. When it comes to long-term, or habitual, exercise, it is established that it has beneficial effects on different aspects of mental health and physical activity interventions are helpful for people with mental illness. The most widely studied mental health-issues are depression, anxiety, and stress, and a recent umbrella review concludes that habitual exercise is beneficial for symptom reduction for depression, anxiety, and stress across different populations. Epidemiological evidence shows that physical activity is associated with lowered risk of experiencing fatigue and reduced energy. Little is known about how physical activity in general and more specifically different intensities of physical activity affects people with ED. Does it have adverse effects or is it beneficial? This is imperative when it comes to intervention- and treatment planning for these patients. No studies have been done specifically on ED before with this focus. Although an acute study cannot show the optimal physical activity program, it can give insight into the relation between between ED and exercise. This in turn can help us construct better designs of exercise programs for this patient group. Research aims and questions The purpose of the study is to gain increased understanding of the psychological and physiological response to acute exercise in ED-patients compared to a healthy population, and to determine if that response differs between two different intensities of exercise (low and moderate). The focus is on transient emotional states and how they might fluctuate in response to exercise. Specifically subjective feelings of fatigue, energy, anxiety, psychological discomfort, perceived exertion, recovery, and stress is studied. Salivary cortisol and heart rate variability (HRV) are the biomarkers in focus. Knowledge from the study is planned to be used in the designing of a physical activity program as part of a treatment program for ED. The design can give us information about whether short bouts of exercise can have mood-altering effects in this patient group, and auonomic reactivity to physical activity. Research questions: 1. Does level of fatigue, vigor/energy, state anxiety, and perceived stress differ between groups (ED/controls) and/or between exercise intensities (mild/moderate) and/or between timepoints (pre/post/30minpost/6hpost/24hpost)? 2. Does the level of subjective discomfort and perceived exertion differ between groups (ED/controls) and/or between exercise intensities (mild/moderate) and/or between time points (pre/5min/10min/15min)? 3. Does the level of salivary cortisol differ between groups (ED/controls) and/or between exercise intensities (mild/moderate) and/or between time points (pre/post/30 min post)? 4. Does level of heart rate variability (HRV) differ between groups (ED/controls) and/or between exercise intensities (mild/moderate) and/or between timepoints (pre/post/30minpost/6hpost/24hpost)? If significant differences are found, intercation effects between the different variables will also be studied, as well as potential moderating variables. Methods Study design The design is a two-armed trial (low and moderate intensity of physical activity) with two groups, one which is patients with ED, and the other an age- and sex matched control group with overall healthy individuals, that include sequential assessments of fatigue and energy states, stress, perceived exertion, perceived psychological distress and state anxiety. Participants Approximately 30 patients with diagnosed exhaustion disorder (F43.8A in ICD-10-SE) and 30 age- and sex-matched healthy control participants are recruited for the study. ED-patients are recruited through occupational health care Avonova and through advertisement in social media Facebook and Instagram. Inclusion criteria in the studies for ED-patients: confirmed primary diagnosis ED by a physician; assessed to not be in the acute phase of ED; age of 35-55 years; considered by a physician and/or a psychologist as suitable for participating in a study including performing physical activity. Healthy control participants are recruited via the same social media channels as ED-patients. Inclusion criteria: age of 35-55 years; self-reported good health (no known somatic or psychiatric disease); considered as suitable for participating in a study including performing physical activity. Mini International Neuropsychiatric Interview 6.0.0. (MINI), as well as an additional diagnostic questionnaire targeting stress-related disorders based on diagnostic criteria from ICD-11, will be conducted with both ED-patients and healthy controls, to ensure the inclusion- and exclusion criteria. MINI is a diagnostic interview for the major DSM-IV psychiatric disorders. The participants will receive thorough written information about the study and written informed consent will be obtained before inclusion. The study was approved by the Regional Ethical Review Board in Linköping, Sweden (Approval Nr. 2022-04943-01) and will be conducted in accordance with the ethical principles of the Declaration of Helsinki. Procedure The study takes place in a laboratory setting at GIH on three different days, separated by at least one week. Before enrollment, participants complete an online administered screening questionnaire measuring exhaustion, burnout, and diagnostic and general health information. Eligible participants are invited to GIH for a familiarization visit, where a structured clinical interview (MINI and stress diagnoses questionnaire) is performed. Participants will also complete a submaximal cardiorespiratory fitness test (CRF) to estimate maximal aerobic capacity. The test is performed on a calibrated mechanically braked cycle ergometer (model 828E, Monark, Varberg, Sweden) for 8 min. Pedal frequency throughout the test is 60 rpm. Cycling resistance starts at 0,5 kilopond (kp) for 4 minutes and is increased to a personalized higher work rate, which lasts for 4 minutes. VO2max is estimated from these 8 minutes using heart rate data collected during the test. The result on this test will be used in determining each participant's correct intensity level on the two trial conditions. Conditions The two trial conditions are performed in a counter-balanced and randomly assigned order. The participants perform the two conditions of physical activity bouts at approximately the same time in the morning/forenoon (start time of test visit is either 8:30 or 10:30 a.m.) with at least one week in between conditions. The participants have the same test start time at the two test visits. At each test session participants perform a 22-minute exercise on a cycle ergometer (model 839E, Monark, Varberg, Sweden). Immediately before and at three time points during the exercise (after 5, 10, and 15 minutes on the low or moderate intensity), they rate level of exertion (RPE) and feelings of psychological distress on a VAS-scale. Immediately before, immediately after, 30 minutes after, 6 hours after, and 24 hours after exercise participants fill out questionnaires regarding feelings of fatigue, energy, anxiety, recovery, and stress. Participants wear a H10 heart rate sensor and Vantage M2 monitor (Polar, Kempele, Finland) for a little more than 24 hours, starting approximately 30 minutes before the exercise. HRV parameters will be calculated from 5-min window recordings using the software Kubios HRV (University of Eastern Finland, Kuopio, Finland), immediately before (pre), immediately after (post), 30 minutes after (30 min post), 6 hours after (6h post), and 24 hours after (24h post) exercise. Since HRV is influenced by several factors (caffeine intake, alcohol consumption, circadian rhythm, stress (both mental and physical), exercise, food- and water intake, certain medications, bladder filling, respiratory rate, and posture) these factors will be controlled for when at GIH. Salivary cortisol is collected pre, post and 30 min post exercise using Sarstedt Salivette Cortisol (Sarstedt, Nümbrecht, Germany). The follow-up measurements will determine the trajectory of the cortisol and HRV post-exercise. During the 24 hours following the exercise bout physical activity pattern is measured using a hip-worn accelerometer (Actigraph GT3X). Accelerometer data will be processed in Actilife. There are two experimental exercise conditions, where participants will exercise at two different intensity levels. The intensity levels are standardized across participants by using results from EKBLOM-BAK test to determine a low and moderate intensity. Low intensity is defined as 40% and moderate intensity is defined as 55% of the participant's individual estimated VO2max. The 22-minute exercise starts with a 6-minute warm-up, with a load increase after 1 and 3 minutes and lowered load at the last minute. Then follows a 15-minute bout on either low or moderate intensity, that ends with a 1-minute cool-down. One of the researchers will be present during the complete test to assure correct intensity and length. Baseline measures In the week before the familiarization visit each participant completes a digitally administered questionnaire that includes socio-demographic and general health information together with the following questionnaires: * Exhaustion disorder. Karolinska Exhaustion Disorder Scale (KEDS) was developed for the assessment of ED symptoms. It consists of nine items with a scale range of 0-54 and a cut-off of 19 has been proposed in the discrimination between healthy subjects and patients with ED. * Burnout. Shirom-Melamed Burnout Questionnaire/Measure (SMBQ/SMBM) is widely used in measuring burnout. SMBM-12 is a short version with twelve items which captures core concepts of burnout: emotional and physiological exhaustion (e.g., "I feel tired"), and cognitive weariness (e.g., "I feel I am not thinking clearly"). A global score of burnout is calculated. SMBM-12 has good composite reliability and convergent validity. * Trait anxiety. The trait subscale of The State-Trait Anxiety Inventory (STAI). Respondents rate how they generally feel on a 4-point Likert Scale (e.g., "I feel nervous and rested"). A global score of a general and enduring trait anxiety is calculated. * Depression. Patient Health Questionnaire (PHQ-9) measures depression in line with DSM-IV. Respondents rate depression symptoms the last two weeks on a 4-point Likert Scale (e.g., "Little interest or pleasure in doing things"). * Sleep. Pittsburgh Sleep Quality Index (PSQI) is widely used in measuring sleep quality. It consists of 19 items that form seven components of retrospective sleep quality (1 month) and a global score. * Physical activity. Saltin-Grimby Physical Activity Level Scale (SGPALS) is a four-level single-item instrument which has acceptable validity for measuring level of physical activity. * Exercise attitudes. Two subscales of the Exercise Benefits/Barriers Scale (EBBS) were included: Psychological Outlook Subscale (benefits), and Physical Exertion Subscale (barriers). 2-3 days after the familiarization visit, heart rate variability (HRV) and physical activity pattern is measured during a 24-hour baseline measurement. Participants get oral and written instructions on the familiarization visit on how to initialize and conduct this measurement with a H10 heart rate sensor and Vantage M2 monitor together with a hip-worn accelerometer (Actigraph GT3X). Twice during the 24h-measurement, digital questionnaires including Single Item stress Question (SISQ), the vigor and fatigue subscales of Profile of Mood States (POMS), single-item recovery question, and state subscale of The State-Trait Anxiety Inventory (STAI-Y1) are completed. Data analysis For each of the psychological variables (perceived exertion, psychological discomfort, fatigue, energy/vigor, state anxiety, and stress) a three factorial (group, time, intensity) ANOVA with repeated measures design will be the first hand choice if parametric assumptions are met. A secondary stratified analysis will be performed exploring potential variables that influenced the primary and secondary psychological variables. For the data analysis of physiological variables, data analysis are yet to be decided. This will be done though before looking at the data. ### Conditions Module **Conditions:** - Exhaustion; Syndrome **Keywords:** - burnout - fatigue - psychological stress - physical activity - acute exercise - mood - heart rate variability ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER **Intervention Model Description:** The design is a two-armed intervention with two groups (30+30), one which is patients with ED, and the other an age- and sex matched control group with overall healthy individuals. The two trial conditions will be performed in a counter-balanced randomized order on two separate days with at least one week apart. Participants will be randomized regarding order of two different intensities of physical activity bouts. The participants will perform the two conditions of physical activity bouts at approximately the same time in the morning/forenoon with at least 1 week in between conditions. ##### Masking Info **Masking:** NONE **Primary Purpose:** BASIC_SCIENCE #### Enrollment Info **Count:** 60 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients with diagnosed exhaustion disorder (F43.8A in Swedish ICD-10). **Intervention Names:** - Behavioral: Acute exercise low intensity - Behavioral: Acute exercise moderate intensity **Label:** Exhaustion disorder (ED) **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Age- and sex-matched healthy control participants. **Intervention Names:** - Behavioral: Acute exercise low intensity - Behavioral: Acute exercise moderate intensity **Label:** Control group **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Control group - Exhaustion disorder (ED) **Description:** A 15-minute exercise on low intensity on a cycle ergometer. Immediately before, immediately after and 30 minutes after exercise participants will fill out questionnaires regarding feelings of fatigue, energy, anxiety and stress and measure saliva cortisol. Three times during the exercise, they will rate level of exertion (RPE) and feelings of distress on a VAS-scale. During the 24 hours following the exercise bout they will wear a heart rate strap and an accelerometer measuring heart rate variability and activity level. Twice during that time, once in the evening, and once in the morning after, participants will answer questionnaires regarding mood state. **Name:** Acute exercise low intensity **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - Control group - Exhaustion disorder (ED) **Description:** A 15-minute exercise on moderate intensity on a cycle ergometer. Immediately before, immediately after and 30 minutes after exercise participants will fill out questionnaires regarding feelings of fatigue, energy, anxiety and stress and measure saliva cortisol. Three times during the exercise, they will rate level of exertion (RPE) and feelings of distress on a VAS-scale. During the 24 hours following the exercise bout they will wear a heart rate strap and an accelerometer measuring heart rate variability and activity level. Twice during that time, once in the evening, and once in the morning after, participants will answer questionnaires regarding mood state. **Name:** Acute exercise moderate intensity **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** Fatigue is defined as "a persistent sense of physical, emotional, and/or cognitive tiredness or exhaustion". Feelings of energy and fatigue is measured with the vigor and fatigue subscales of Profile of Mood States (POMS). It assesses short-term mood states and respondents are instructed to rate how the feel "right now". The total score ranges from 0 to 28 and a higher score means a worse outcome. It is a valid and reliable measure of intensities of fatigue and energy mood states and is recommended to be used in experimental settings to measure short-term intensity of energy and fatigue moods. **Measure:** Fatigue **Time Frame:** Fatigue is measured in both conditions at the following time-points: immediately before the exercise bout, immediately after the exercise bout, 30 minutes after the exercise bout, 6 hours after the exercise bout, and 24 hours after the exercise bout. **Description:** The adopted definition of energy is "an individual's potential to perform mental and physical activity". Feelings of energy and fatigue is measured with the vigor and fatigue subscales of Profile of Mood States (POMS). It assesses short-term mood states and respondents are instructed to rate how the feel "right now". The total score ranges from 0 to 32 and a higher score means a better outcome. It is a valid and reliable measure of intensities of fatigue and energy mood states and is recommended to be used in experimental settings to measure short-term intensity of energy and fatigue moods. **Measure:** Energy/vigor **Time Frame:** Energy/vigor is measured in both conditions at the following time-points: immediately before the exercise bout, immediately after the exercise bout, 30 minutes after the exercise bout, 6 hours after the exercise bout, and 24 hours after the exercise bout **Description:** State anxiety will be measured using the 20-item state subscale of The State-Trait Anxiety Inventory (STAI-Y1). Respondents rate how they feel "right now" on a 4-point Likert Scale (e.g., "I am tense"). A global score of the transient condition of state anxiety is calculated, ranging from 20 to 80. Higher scores correlates with greater anxiety. It is extensively used in previous studies of acute exercise and there is support for the STAI-Y1 being sensitive to change in response to acute aerobic exercise. **Measure:** State anxiety **Time Frame:** State anxiety is measured in both conditions at the following time-points: immediately before the exercise bout, immediately after the exercise bout, 30 minutes after the exercise bout, 6 hours after the exercise bout, and 24 hours after the exercise bou #### Secondary Outcomes **Description:** To measure subjective stress in the moment the Single Item stress Question (SISQ) was adapted and reformulated to measure stress "right now" instead of "these days". The scale ranges from 1 to 5, and higher scores correlates with higher level of stress. **Measure:** Stress. **Time Frame:** Stress is measured in both conditions at the following time-points: immediately before the exercise bout, immediately after the exercise bout, 30 minutes after the exercise bout, 6 hours after the exercise bout, and 24 hours after the exercise bout. **Description:** Subjective Units of Distress (SUD) is used to assess the strength of subjective discomfort during the exercise bout. The respondent is asked to rate on a scale from 0 to 10 how much discomfort they experience. The scale ranges from 0 10 and a higher score indicates more discomfort. **Measure:** Perceived psychological discomfort. **Time Frame:** SUD is measured in both conditions at the following time-points: immediately before the exercise bout; during the exercise at 3 time points: 5 min into the exercise, 10 min into the exercise, and 15 min into the exercise **Description:** Borg's 6-20 rating of perceived exertion scale (RPE) was used to assess exertion during exercise. It is a single-item scale ranging from 6 (not strenuous at all) to 20 (maximally strenuous). **Measure:** Perceived Exertion. **Time Frame:** RPE is measured in both conditions at the following time-points: immediately before the exercise bout; during the exercise at 3 time points: 5 min into the exercise, 10 min into the exercise, and 15 min into the exercise **Description:** Is used as a biomarker indicator of the HPA-axis response to exercise. Saliva is collected with standard swabs; Sarstedt Salivette Cortisol, then stored and analyzed following standard procedures. **Measure:** Salivary cortisol **Time Frame:** Cortisol is measured in both conditions at the following time points: 10 minutes before each exercise bout; 5 minutes after each exercise bout; and 35 minutes after each exercise bout. **Description:** Specific measures still to be decided upon. This will be decided before looking at the data. **Measure:** Heart rate variablity (HRV) **Time Frame:** HRV is measured in both conditions at the following time points: 5 minutes before exercise bout; ca 8 minutes after exercise bout; and ca 38 minutes after exercise bout. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: For ED-patients: * Confirmed primary diagnosis ED by a physician * Assessed to not be in the acute phase of ED * considered by a physician and/or a psychologist as suitable for participating in a study including performing physical activity * Age of 35-55 years For control group: * Self-reported good health (no known somatic or psychiatric disease) * Age of 35-55 years Exclusion Criteria: * Chronic fatigue syndrome (CFS) * Post-covid * Dementia * Bipolar and/or psychotic disorder * Current substance abuse * Fibromyalgia * Elevated suicide risk * Medication with beta-blockers Following exclusion criteria is also used, since it is not suitable to perform the EKBLOM-BAK-test: * chronic obstructive lung disease * hypertension/dyslipidemia * cardiovascular disease If participant has ongoing infection (such as a cold) on testday, testing is delayed until she/he is recovered. **Healthy Volunteers:** True **Maximum Age:** 55 Years **Minimum Age:** 35 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Stockholm **Country:** Sweden **Facility:** Victoria Blom **Zip:** 11433 #### Overall Officials **Official 1:** **Affiliation:** The Swedish School of Sport and Health Sciences **Name:** Victoria Blom, Ass. prof. **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Almén, N., & Jansson, B. (2021). The reliability and factorial validity of different versions of the Shirom-Melamed Burnout Measure/Questionnaire and normative data for a general Swedish sample. International Journal of Stress Management, 28(4), 314-325. https://doi.org/10.1037/str0000235 **Citation:** Bjorkman F, Ekblom-Bak E, Ekblom O, Ekblom B. Validity of the revised Ekblom Bak cycle ergometer test in adults. Eur J Appl Physiol. 2016 Sep;116(9):1627-38. doi: 10.1007/s00421-016-3412-0. Epub 2016 Jun 16. **PMID:** 27311582 **Citation:** Borg G, Ljunggren G, Ceci R. The increase of perceived exertion, aches and pain in the legs, heart rate and blood lactate during exercise on a bicycle ergometer. Eur J Appl Physiol Occup Physiol. 1985;54(4):343-9. doi: 10.1007/BF02337176. **PMID:** 4065121 **Citation:** Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989 May;28(2):193-213. doi: 10.1016/0165-1781(89)90047-4. **PMID:** 2748771 **Citation:** World Health Organization: The ICD-10 classification of mental and behavioural disorders: Clinical descriptions and diagnostic guidelines. Geneva: World Health Organization, 1992. **Citation:** Lindsater E, Svardman F, Wallert J, Ivanova E, Soderholm A, Fondberg R, Nilsonne G, Cervenka S, Lekander M, Ruck C. Exhaustion disorder: scoping review of research on a recently introduced stress-related diagnosis. BJPsych Open. 2022 Aug 24;8(5):e159. doi: 10.1192/bjo.2022.559. **PMID:** 36458830 **Citation:** Singh B, Olds T, Curtis R, Dumuid D, Virgara R, Watson A, Szeto K, O'Connor E, Ferguson T, Eglitis E, Miatke A, Simpson CE, Maher C. Effectiveness of physical activity interventions for improving depression, anxiety and distress: an overview of systematic reviews. Br J Sports Med. 2023 Sep;57(18):1203-1209. doi: 10.1136/bjsports-2022-106195. Epub 2023 Feb 16. **PMID:** 36796860 **Citation:** Spielberger, C.D., Gorsuch, R.L., & Lushene, R.E. (1970). The State-Trait Anxiety Inventory: Testmanual. Palo Alto, CA: Consulting Psychologist Press **Citation:** Saltin B, Grimby G. Physiological analysis of middle-aged and old former athletes. Comparison with still active athletes of the same ages. Circulation. 1968 Dec;38(6):1104-15. doi: 10.1161/01.cir.38.6.1104. No abstract available. **PMID:** 5721960 **Citation:** Sechrist KR, Walker SN, Pender NJ. Development and psychometric evaluation of the exercise benefits/barriers scale. Res Nurs Health. 1987 Dec;10(6):357-65. doi: 10.1002/nur.4770100603. **PMID:** 3423307 **Citation:** Tiwari R, Kumar R, Malik S, Raj T, Kumar P. Analysis of Heart Rate Variability and Implication of Different Factors on Heart Rate Variability. Curr Cardiol Rev. 2021;17(5):e160721189770. doi: 10.2174/1573403X16999201231203854. **PMID:** 33390146 **Citation:** Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59 Suppl 20:22-33;quiz 34-57. **PMID:** 9881538 **Citation:** Puetz TW. Physical activity and feelings of energy and fatigue: epidemiological evidence. Sports Med. 2006;36(9):767-80. doi: 10.2165/00007256-200636090-00004. **PMID:** 16937952 **Citation:** Paluska SA, Schwenk TL. Physical activity and mental health: current concepts. Sports Med. 2000 Mar;29(3):167-80. doi: 10.2165/00007256-200029030-00003. **PMID:** 10739267 **Citation:** Rosenbaum S, Tiedemann A, Sherrington C, Curtis J, Ward PB. Physical activity interventions for people with mental illness: a systematic review and meta-analysis. J Clin Psychiatry. 2014 Sep;75(9):964-74. doi: 10.4088/JCP.13r08765. **PMID:** 24813261 **Citation:** Mikkelsen K, Stojanovska L, Polenakovic M, Bosevski M, Apostolopoulos V. Exercise and mental health. Maturitas. 2017 Dec;106:48-56. doi: 10.1016/j.maturitas.2017.09.003. Epub 2017 Sep 7. **PMID:** 29150166 **Citation:** Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001 Sep;16(9):606-13. doi: 10.1046/j.1525-1497.2001.016009606.x. **PMID:** 11556941 **Citation:** Garber CE, Blissmer B, Deschenes MR, Franklin BA, Lamonte MJ, Lee IM, Nieman DC, Swain DP; American College of Sports Medicine. American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Med Sci Sports Exerc. 2011 Jul;43(7):1334-59. doi: 10.1249/MSS.0b013e318213fefb. **PMID:** 21694556 **Citation:** Beser A, Sorjonen K, Wahlberg K, Peterson U, Nygren A, Asberg M. Construction and evaluation of a self rating scale for stress-induced exhaustion disorder, the Karolinska Exhaustion Disorder Scale. Scand J Psychol. 2014 Feb;55(1):72-82. doi: 10.1111/sjop.12088. Epub 2013 Nov 15. **PMID:** 24236500 **Citation:** Tanner BA. Validity of global physical and emotional SUDS. Appl Psychophysiol Biofeedback. 2012 Mar;37(1):31-4. doi: 10.1007/s10484-011-9174-x. **PMID:** 22038278 **Citation:** Arapovic-Johansson B, Wahlin C, Kwak L, Bjorklund C, Jensen I. Work-related stress assessed by a text message single-item stress question. Occup Med (Lond). 2017 Dec 2;67(8):601-608. doi: 10.1093/occmed/kqx111. **PMID:** 29016877 **Citation:** Ensari I, Greenlee TA, Motl RW, Petruzzello SJ. META-ANALYSIS OF ACUTE EXERCISE EFFECTS ON STATE ANXIETY: AN UPDATE OF RANDOMIZED CONTROLLED TRIALS OVER THE PAST 25 YEARS. Depress Anxiety. 2015 Aug;32(8):624-34. doi: 10.1002/da.22370. Epub 2015 Apr 21. **PMID:** 25899389 **Citation:** Herring MP, Monroe DC, Gordon BR, Hallgren M, Campbell MJ. Acute Exercise Effects among Young Adults with Analogue Generalized Anxiety Disorder. Med Sci Sports Exerc. 2019 May;51(5):962-969. doi: 10.1249/MSS.0000000000001860. **PMID:** 30531490 **Citation:** Loy BD, Cameron MH, O'Connor PJ. Perceived fatigue and energy are independent unipolar states: Supporting evidence. Med Hypotheses. 2018 Apr;113:46-51. doi: 10.1016/j.mehy.2018.02.014. Epub 2018 Feb 19. **PMID:** 29523293 **Citation:** McNair D. M., Lorr M., & Droppleman L. Profile of Mood States questionnaire. San Diego (CA): EDITS, 1981. **Citation:** O'Connor PJ. Evaluation of four highly cited energy and fatigue mood measures. J Psychosom Res. 2004 Nov;57(5):435-41. doi: 10.1016/j.jpsychores.2003.12.006. **PMID:** 15581646 **Citation:** Sagelv EH, Hopstock LA, Johansson J, Hansen BH, Brage S, Horsch A, Ekelund U, Morseth B. Criterion validity of two physical activity and one sedentary time questionnaire against accelerometry in a large cohort of adults and older adults. BMJ Open Sport Exerc Med. 2020 Feb 26;6(1):e000661. doi: 10.1136/bmjsem-2019-000661. eCollection 2020. **PMID:** 32153981 ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M16105 - Name: Stress, Psychological - Relevance: LOW - As Found: Unknown - ID: M8364 - Name: Fatigue - Relevance: LOW - As Found: Unknown - ID: M1658 - Name: Burnout, Psychological - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Browse Branches - Abbrev: Infl - Name: Anti-Inflammatory Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M9912 - Name: Hydrocortisone - Relevance: LOW - As Found: Unknown - ID: M155245 - Name: Hydrocortisone 17-butyrate 21-propionate - Relevance: LOW - As Found: Unknown - ID: M228609 - Name: Hydrocortisone acetate - Relevance: LOW - As Found: Unknown - ID: M263259 - Name: Hydrocortisone hemisuccinate - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429410 **Brief Title:** Effects of Milk Powder Intervention on Body Composition and Physical Performance in Middle-aged and Older Adults **Official Title:** Effects of Daily Supplementation With Milk Powder on Body Composition and Physical Performance in Middle-aged and Older Adults: A Randomized Control Trial #### Organization Study ID Info **ID:** MN-2024-04 #### Organization **Class:** OTHER **Full Name:** Sun Yat-sen University ### Status Module #### Completion Date **Date:** 2026-07 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2026-07 **Type:** ESTIMATED #### Start Date **Date:** 2024-05 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-16 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Huilian Zhu #### Responsible Party **Investigator Affiliation:** Sun Yat-sen University **Investigator Full Name:** Huilian Zhu **Investigator Title:** Professor **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** This study aims to conduct a 24-week intervention involving formula milk powder for middle-aged and elderly individuals, assessing its impact on body composition and physical performance in comparison to interventions using regular milk powder and individuals without intervention. ### Conditions Module **Conditions:** - Healthy ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** TRIPLE **Who Masked:** - PARTICIPANT - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** BASIC_SCIENCE #### Enrollment Info **Count:** 200 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Fortified formula milk powder is supplemented with whey protein, calcium, vitamin D, colostrum basic protein, β-hydroxy-β-methylbutyrate, and sodium hyaluronate, and packaged in 25-gram sachets. The milk powder is consumed orally, two sachets per day, for a duration of 24 weeks. **Intervention Names:** - Dietary Supplement: fortified formula milk powder **Label:** fortified formula milk powder group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Formula milk powder is supplemented with whey protein, calcium, vitamin D, colostrum basic protein, and sodium hyaluronate, and packaged in 25-gram sachets. The milk powder is consumed orally, two sachets per day, for a duration of 24 weeks. **Intervention Names:** - Dietary Supplement: formula milk powder **Label:** formula milk powder group **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Regular milk powder does not contain and additional supplementation, and the color, flavor, shape, taste, and weight are same with the formula milk powder. **Intervention Names:** - Dietary Supplement: regular milk powder **Label:** regular milk powder group **Type:** PLACEBO_COMPARATOR #### Arm Group 4 **Description:** Participants in the observation group did not receive any supplementation. **Label:** observation group **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - fortified formula milk powder group **Description:** Fortified formula milk powder supplemented with whey protein, calcium, vitamin D, colostrum basic protein, β-hydroxy-β-methylbutyrate, and sodium hyaluronate per day orally for 24 weeks. **Name:** fortified formula milk powder **Type:** DIETARY_SUPPLEMENT #### Intervention 2 **Arm Group Labels:** - formula milk powder group **Description:** Formula milk powder supplemented with whey protein, calcium, vitamin D, colostrum basic protein, and sodium hyaluronate per day orally for 24 weeks. **Name:** formula milk powder **Type:** DIETARY_SUPPLEMENT #### Intervention 3 **Arm Group Labels:** - regular milk powder group **Description:** Regular milk powder does not contain and additional supplementation, and the color, flavor, shape, taste, and weight are same with the formula milk powder. **Name:** regular milk powder **Type:** DIETARY_SUPPLEMENT ### Outcomes Module #### Primary Outcomes **Description:** At baseline, and 24 weeks, investigators will use DXA to examine lean body mass and fat composition. **Measure:** lean body mass **Time Frame:** up to 24 weeks #### Secondary Outcomes **Description:** At baseline, and 24 weeks, investigators will use cardiopulmonary exercise testing (CPET) on a cycle ergometer to evaluate cardiorespiratory fitness. **Measure:** cardiorespiratory fitness **Time Frame:** up to 24 weeks **Description:** At baseline, 12, and 24 weeks, investigators will test hand grip to assess muscle strength. **Measure:** muscle strength **Time Frame:** up to 24 weeks **Description:** At baseline, 12, and 24 weeks, investigators will test the Short Physical Performance Battery (SPPB) to assess muscular function. **Measure:** physical performance **Time Frame:** up to 24 weeks **Description:** At baseline, and 24 weeks, blood samples will be drawn and serum indexes of bone and muscle metabolism will be test, including myostatin, PINP, CTx, and osteocalcin. **Measure:** the levels of blood metabolic markers for bone and muscle **Time Frame:** up to 24 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Aged 50 years old and older; * BMI \<22kg/m2; * Calf circumference \<33cm in women or \<34cm in men, or SARC-F ≥ 4, or SARC-Claf ≥ 11; * Living in Guangzhou and having no plan to move in the next 6 months; * Willing to participate in the study. Exclusion Criteria: * Lactose intolerance; * Complicated with severe diseases; * Unable to conduct study procedures; * Participating in any other intervention studies. **Healthy Volunteers:** True **Minimum Age:** 50 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ## Derived Section ### Intervention Browse Module - Browse Branches - Abbrev: Micro - Name: Micronutrients - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: BDCA - Name: Bone Density Conservation Agents - Abbrev: Vi - Name: Vitamins - Abbrev: Ot - Name: Other Dietary Supplements ### Intervention Browse Module - Browse Leaves - ID: M17558 - Name: Vitamins - Relevance: LOW - As Found: Unknown - ID: M9878 - Name: Hyaluronic Acid - Relevance: LOW - As Found: Unknown - ID: M17550 - Name: Vitamin D - Relevance: LOW - As Found: Unknown - ID: M6003 - Name: Cholecalciferol - Relevance: LOW - As Found: Unknown - ID: M5381 - Name: Calcium - Relevance: LOW - As Found: Unknown - ID: M5398 - Name: Calcium, Dietary - Relevance: LOW - As Found: Unknown - ID: T442 - Name: Cholecalciferol - Relevance: LOW - As Found: Unknown - ID: T479 - Name: Vitamin D3 - Relevance: LOW - As Found: Unknown - ID: T440 - Name: Calciferol - Relevance: LOW - As Found: Unknown - ID: T435 - Name: Whey Protein - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429397 **Brief Title:** First-line Anlotinib Combined With Penpulimab for Advanced Pheochromocytoma: A Single-arm, Multicenter, Prospective Phase II Study **Official Title:** A Single-arm, Multicenter, Prospective Phase II Clinical Study of Anlotinib Combined With Penpulimab in the First-line Treatment of Advanced Pheochromocytoma/Paraganglioma #### Organization Study ID Info **ID:** 2023-FXY-304 #### Organization **Class:** OTHER **Full Name:** Sun Yat-sen University ### Status Module #### Completion Date **Date:** 2026-05-28 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-05-20 **Type:** ACTUAL #### Start Date **Date:** 2024-05-15 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-04-08 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Chia Tai Tianqing Pharmaceutical Group Co., Ltd. #### Lead Sponsor **Class:** OTHER **Name:** Sun Yat-sen University #### Responsible Party **Investigator Affiliation:** Sun Yat-sen University **Investigator Full Name:** ZHOU FANGJIAN **Investigator Title:** Sun Yat-sen University Cancer Center **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** There is currently no standard first-line treatment for stage PPGL, and the 5-year survival rate of patients with advanced pheochromocytoma/paraganglioma (PPGL) is low, ranging from 30% to 60%. At present, several domestic teams have carried out clinical studies on the treatment of advanced PPGL with good efficacy. In the early stage, our center used anrotinib to treat advanced PPGL, and the overall effective rate reached 44%. In the early stage, our team used anrotinib combined with PD-1 monoclonal antibody to treat advanced PPGL patients. The effective rate reached 66% (2/3). Therefore, the investigators plan to further conduct prospective studies to explore the efficacy and safety of anlotinib combined with PD-1 monoclonal antibody in the treatment of advanced PPGL, so as to bring benefits to patients with advanced PPGL. **Detailed Description:** 1.1 Adrenal pheochromocytoma/paraganglioma pheochromocytoma (PCC) and Paraganglioma (PGL) (pheochromocytoma and paraganglioma (PPGL) are rare malignant tumors with neuroendocrine function and metastatic potential. The incidence is 0.4-2.1 persons/million, 80%-85% originate from the adrenal medulla, and 15%-20% originate from the neural crest tissue from the neck to the pelvis. The PPGL metastasis rate at initial diagnosis is 10%, and the risk of metastasis is as high as 34-69% for those with SDHB gene mutations. The recurrence rate of PPGL patients after radical resection was 30%, 47% recurred with multiple nodules, 58% with metastasis. The most common sites of metastasis were lymph nodes and bone (70-80%), followed by lung and liver (50%). In addition, some PPGL is difficult/unresectable due to its proximity to important structures such as large blood vessels or nerves, and the 5-year survival rate for advanced PPGL is 30%-60%. Early PPGL can be cured by surgery, but late PPGL is mainly systemic therapy, such as chemotherapy, targeted drugs and nuclide therapy. The main chemotherapy regimen for advanced PPGL is cyclophosphamide - vincristine - dacarbazine (CVD regimen), and ESMO guidelines recommend CVD for patients with rapid tumor progression and heavy tumor burden. The objective response rate of CVD regimen was 33%, the median duration of response was 1.3 years, and the 5-year survival rate of patients with effective CVD was 51%. The main limitations of CVD in the treatment of advanced PPGL are (1) The average number of cycles required for CVD chemotherapy is 11.6±10.8 months; (2) The incidence of CVD related toxicity, such as bone marrow suppression and neurotoxicity, was 50%. Some patients could not maintain treatment due to intolerance, and long-term use of the above drugs could increase the incidence of hematological tumors, which may be related to the alkylating properties of daparbazine. Domestic guidelines and the FDA recommend 131I-MIBG for the treatment of advanced PPGL. Loh et al. reviewed and analyzed 21 central LSA-131I-MIBG clinical studies: 30% patients could have Partial Response (PR); Gonias S et al. Phase II clinical study of HSA-131I-MIBG in the treatment of advanced PPGL: 22% of patients could have PR. Two 131I-MIBGs show good efficacy, but there are no phase III clinical studies to further validate efficacy and safety. Limitations of radionuclide therapy lie in (1) the narrow range of indications: (1) ESMO guidelines indicate that only 50% of patients with positive MIBG scan are suitable. ② Pregnant women and pregnant patients should not use; (2) Severe hematological toxicity: the incidence of myosuppression was 4%-79%, about 40% of patients treated with low-dose 131I-MIBG had grade 3/4 toxicity, while those treated with high-dose 131I-MIBG had up to 80%, of which 25% needed hematological therapy and secondary hematological tumors could be developed . (3) Hypogonadism. In addition, at present, the units that can carry out nuclide therapy in China are limited, and patients can not perform nuclide therapy again after receiving progress of nuclide therapy. 1.2 Tyrosine kinase inhibitors (TKI) and advanced adrenal pheochromocytoma/paraganglioma Tyrosine kinase (TK) is a key site in the activation and regulation of cell proliferation signaling pathways. Abnormal TK pathway caused by mutation, translocation or amplification can lead to tumor occurrence, progression, invasion and metastasis. Tyrosine kinase inhibitors (TKI) mainly act on vascular endothelial growth factor receptor (VEGFR), platelet growth factor (PDGFR) and insulin family receptor (InsR). TKI acts on advanced PPGL through the pseudo-hypoxia pathway and VEGF angiogenesis pathway. Advanced PPGL with abundant blood supply and high expression of angiogenic factor (VEGF) can promote tumor neovascularization and provide oxygen and nutrition for tumors. TKI has a good therapeutic effect on advanced PPGL with high VEGF expression, which may be related to its blocking of VEGF signaling pathway, continuous inhibition of tumor neovascugenesis and promotion of abnormal blood vessel normalization. In addition, HIF axis misalignment can also promote the development and transfer of PPGL. SDH gene mutations are the most common in PPGL (including SDHA, SDHB, SDHC, SDHD), which cause abnormalities in the subunit encoding the succinate dehydrogenase complex (SDH) and block the tricarboxylic acid cycle (TCA). Abnormal TCA can inhibit hypoxia-inducing factor (HIF-α) proline hydroxylase, and HIF-α accumulation will activate the pseudo-hypoxia pathway and up-regulate the expression of VEGF and other factors. ESMO guidelines recommend sunitinib for the treatment of advanced PPGL. Currently, the only prospective phase II clinical study showed that 3 cases (13%) had PR (SDHB, SDHD, RET gene mutations, respectively). A retrospective study of 17 cases of advanced PPGL treated by MD Anderson and Gustavvy-Roussy et al. showed that there were 3 cases of PR and 5 cases of SD (6 of which were SDHB or VHL gene mutations). In the study , grade 1-2 toxicity was the most common, with about 68% of patients presenting symptoms such as fatigue, nausea and vomiting, palm-plantar dyspepsia, etc., while only 56%/12% of patients presented 3/4 toxicity, mainly manifested as nausea, vomiting and hypertension, without hematological toxicity. Retrospective studies have also shown that Renvastinib, pazopanib, acitinib and other TKI have certain efficacy in advanced PPGL, but there is a lack of prospective clinical evidence. Hassan Nelson L et al. treated 11 cases of advanced PPGL with lenvatinib, and the results were 5 cases PR, 3 cases SD, and the median PFS was 14.7 months. Mauricio Emmanuel Burotto Pichun et al. are conducting a study on the treatment of 11 cases of advanced PPGL with acitinib: 4 cases of PR and 6 cases of SD. The above studies show the preliminary efficacy of various TKI, and the effect may be better for SDHB mutations, with a controllable safety, mainly hypertension. In 2017, preliminary results of a prospective clinical study of cabotinib in the treatment of advanced PPGL were reported in the conference abstract: ORR of 45%, PFS of 11 months, and no grade 3/4 toxicity. In summary, TKI monotherapy in the treatment of advanced PPGL shows some effect, but it is still not satisfactory. There is currently no standard first-line treatment for advanced PPGL. NCCN guidelines and China's expert consensus (2020 edition) recommend the use of tumor reduction surgery (palliative resection) combined with radiotherapy, radionuclide therapy or systemic chemotherapy and other treatment options, but the above methods have uncertain efficacy and certain limitations, still need to be confirmed by prospective experiments, so patients are recommended to participate in clinical trials. 1.3 Application of antirotinib hydrochloride in advanced adrenal pheochromocytoma/paraganglioma Allotinib (AL3818) is manufactured by Zhengda Tianqing Pharmaceutical Group Co., LTD. (CTTQ; Lianyungang, Jiangsu, China) self-developed TKI drugs, targeting VEGFR1-3, FGFR1-4, PDGFRα, G, β, rearrangement (RET) and stem cell factor receptor (c-Kit) during transfection \[26\]; Anlotinib has shown good anticancer activity in vitro/in vitro \[27\]. A multicentre, randomized, controlled Phase II clinical study of anlotinib in first-line treatment of metastatic renal cell carcinoma (mRCC) (NCT02072031)\[28\] showed similar efficacy of anlotinib and Sunitinib: There were no significant differences in median PFS (17.May vs. 16.June, P \> 0.05), OS, ORR and DCR (P \> 0.05), but the toxicity of anrotinib was lower, and the incidence of ≥3/4 toxicity was significantly lower than that of Sunitinib (28.9% vs.55.8%, P \< 0.01). The main symptoms were hypertension and hand-foot syndrome, and no hematological toxicity was found. In addition, Lin J et al. also confirmed that anlotinib and Sunitinib had similar efficacy but higher safety. TKI treatment of advanced PPGL has a similar mechanism of action, but anlotinib safety may be better. In addition, our team has a certain foundation in the study of anrotinib in the treatment of advanced PPGL. In the early stage, anrotinib monotherapy was used to treat advanced PPGL in 4 cases and PR in 2 cases (1 case was a SHDB mutation), and the adverse reactions were mostly grade 1-2, with hypertension and hand-foot syndrome as the main manifestations. Therefore, antirotinib may have better efficacy and safety in advanced PPGL, which is worthy of further clinical exploration. 1.4 Application of peamprizumab in advanced adrenal pheochromocytoma/paraganglioma PD-1/PD-L1 monoclonal antibody kills tumors by activating its own normal anti-tumor immune mechanism. In 2014, Pembrolizumab achieved results in melanoma, officially ushering in the era of global immunotherapy. Subsequently, indications and significant curative effects were also obtained in multi-tumor species such as non-small cell lung cancer, gastric cancer and kidney cancer. PD-L1 is mainly expressed in tumor cells and antigen-presenting cells (APCs), and is closely related to tumor immune escape \[33\] : PD-L1 receptor of tumor cell membrane binds to PD-1 receptor of T cell membrane, which weakens the ability of cytotoxic T lymphocytes to kill tumor cells. PD-1/PD-L1 mab blocks the above signaling process and restores/activates the anti-tumor activity of T cells. A study in Peking Union Medical College Hospital \[35\] showed that 59.7% were positive for PPGL PD-L1 expression (HIS\>10), and the positive rate of PD-L1 in advanced PPGL was 100%(1/1). Study \[36\] showed that PD-L1 expression was positive in 4 out of 10 advanced PPGL cases (40%). Studies indicated that the cytotoxic T lymphocyte infiltration level was increased in advanced PPGL (P=0.092). Therefore, PD-1 monoclonal antibody may have some significance in the treatment of advanced PPGL. At present, only A few cases have been reported in the treatment of advanced PPGL with PD-1 monoclonal antibody. The Phase II clinical study conducted by Naing A et al. in the treatment of advanced PPGL patients with pembrolizumab showed that 43% (4 cases) had no progress at 27 weeks (6.75 months). This suggests that PD-1 monoclonal antibody has a certain effect in the treatment of advanced PPGL, but PD-1 monotherapy can not meet the clinical needs. KATO Y et al. proposed that the effective rate of PD-1 monoclonal antibody in the single treatment of solid tumors was 20%-30%, and the therapeutic effect was not satisfactory. The study of PD-1 monoclonal antibody combined with TKI in the treatment of liver cancer suggests that the combination of PD-1 monoclonal antibody can reverse the immunosuppressor tumor microenvironment in which PD-1 monoclonal antibody is ineffective, and assist PD-1/PD-L1 monoclonal antibody to activate cytotoxic T lymphocytes. The efficacy of acitinib combined with PD-1 mab in the second-line treatment of patients with metastatic renal cancer was significantly higher than that of acitinib (ORR: 33.6% vs. 20.1%, P=0.015) (PFS: 11.7 months vs. 7.5 months, P=0.002). Piamprilizumab (Anicol) is a new PD-1 monoclonal antibody developed by Zhengda Tianqing Pharmaceutical Group Co., LTD., which has been approved for Hodgkin's lymphoma (R/R cHL) and squamous non-small cell lung cancer (NSCLC) indications in China. Pembrolizumab has achieved significant efficacy in the treatment of classic Hodgkin lymphoma, metastatic nasopharyngeal carcinoma, gastric/esophageal junction adenocarcinoma and other tumor species in clinical studies, with ORR of 89.4%, 29.7% and 26.3%, respectively . Anicol is a humanized IgG1 subtype of PD-1 monoclonal antibody that eliminates Fc effects. The IgG1 subtype reduces immune escape by eliminating antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC). The combination of anil with FcR can reduce the occurrence of adverse immune reactions , and the incidence of grade 3 and above toxicities such as immune-associated pneumonia, hepatitis, myocardium, and pancreatitis is lower than that of sindillizumab, tirellizumab, and triplizumab. Therefore, this study intends to use anicol combined with anlotinib to explore its efficacy and safety in advanced PPGL. 1.5 Application of antirotinib combined with PD-1 monoclonal antibody in advanced pheochromocytoma/paraganglioma The combination of TKI and PD-1 monoclonal antibody is a research hotspot in the treatment of advanced tumors. Target-free therapy has been widely used in renal, urothelial, lung, liver and other tumors, and has achieved remarkable efficacy \[46\]. Only a few cases of combined treatment for advanced PPGL have been reported at home and abroad. In Taizhou Hospital of Zhejiang Province in 2022, a patient was treated with palizumab injection 200 mg(once every 3 weeks) for intravenous immunotherapy, combined with anrotinib 10 mg orally (once a day, 14 days and 7 days, every 3 weeks for a course of treatment). The left adrenal mass (9.6cm →8.4cm) and the multiple intrahepatic mass (up to 9.3cm →8.8cm) were both reduced. In the early stage, our team used anrotinib combined with PD-1 monoclonal antibody to treat 3 patients, and the efficacy reached PR 66% (2/3), including 1 case with SHDB mutation. This suggests that targeted immunotherapy for advanced PPGL may have better efficacy. In an open, multicenter, phase Ib/II clinical study of anlotinib combined with piamprizumab in the treatment of advanced hepatocellular carcinoma, the ORR was 31% and the DCR was 82.8%. The median PFS was 8.8 months (95% CI 4.0-12.3 months). 80% were grade 1/2 toxicity, such as elevated AST, elevated ALT, elevated blood bilirubin, etc. Only 19.4% had grade 3/4 toxicity such as hypertension and rash. This is an improvement in efficacy and a decrease in toxicity compared to the treatment of advanced hepatocellular carcinoma with altilizumab combined with bevacizumab or carrilizumab combined with apatinib. At present, there have been no studies on the combination of targeted drugs and immunodrugs in the treatment of advanced PPGL at home and abroad. Therefore, this study will for the first time apply the combination of TKI drugs (antirotinib) and PD-1 monoclonal antibody (Pembrolizumab) to metastatic/unresectable pheochromocytoma/paraganglioma, so as to explore the efficacy and safety of combined drugs in the treatment of advanced pheochromocytoma/paraganglioma. ### Conditions Module **Conditions:** - Pheochromocytoma ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 22 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients receive Penpulimab and anlotinib **Intervention Names:** - Drug: Anlotinib and Penpulimab **Label:** Drug **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Drug **Description:** Enrolled patients received a treatment cycle every 21 days: 200mg of piamprizumab was given intravenously on the first day of treatment, and 12mg of anrotinib hydrochloride capsule was given continuously for 14 days and suspended for 7 days. **Name:** Anlotinib and Penpulimab **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The sum of the maximum tumor diameter decreased by ≥30% **Measure:** Objective response rate **Time Frame:** 2years #### Secondary Outcomes **Description:** The time before tumor diameters increased by less than 20% **Measure:** progression-free survival **Time Frame:** 2years **Description:** The time before the patient died **Measure:** Overall survival **Time Frame:** 2years **Description:** The duration of tumor remission **Measure:** Duration of remission **Time Frame:** 2years **Description:** the number of patient with PR SD and CR **Measure:** Clinical response rate **Time Frame:** 2years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients voluntarily participate in this study and sign informed consent; * Patients aged ≥18 years and ≤75 years; * ECOG score ≤2 points; Expected survival ≥6 months; * Pathological diagnosis of advanced pheochromocytoma/paraganglioma: including clinical stage IV unresectable pheochromocytoma/paraganglioma with postoperative recurrence or metastasis; * Unwilling or unsuitable for chemotherapy and radionuclide therapy. * At least one measurable lesion (RECIST 1.1); * The main organs function well, and the laboratory examination indicators meet: 1. Blood routine examination: Hemoglobin (HB) ≥ 90g/L(5.6 mmol/L); Absolute neutrophil count (ANC) ≥1.5×109/L; Total white blood cells ≥3.5×109/L; ③ Platelet (PLT) ≥ 80×109/L; Blood biochemical examination: ① Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN (liver metastasis/bone metastasis ≤5 × ULN; Bone metastases ≤5 ULN); ② Serum total bilirubin (TBIL) ≤1.5 × ULN; ③ Serum creatinine Cr≤1.5×ULN or creatinine clearance ≥60 ml/min; Blood urea nitrogen (BUN)≤2.5 × upper limit of normal value (ULN); ④ Albumin (ALB)≥30 g/L; 2. Blood clotting test: * Activated partial thromboplastin time (APTT), International standardized ratio (INR), prothrombin time (PT) ≤ 1.5×ULN; * Women of reproductive age must confirm their non-pregnant status before enrollment, and all enrolled subjects (whether male or female) should take adequate contraceptive measures during the entire treatment period and within 4 weeks after the end of treatment; * The subjects voluntarily joined the study and were willing to return to the hospital for follow-up, and the compliance was good; Myocardial enzymes and ejection fraction were normal. Exclusion Criteria: * known allergic reactions to anrotinib hydrochloride capsules, piamplizumab active ingredients or any excipients; * Receiving anti-tumor monoclonal antibodies or other investigational drugs before enrollment; Previous treatment with other anti-PD-1 monoclonal antibodies or other medications targeting PD-1 / PD-L1; * previous use of anrotinib hydrochloride capsules or other anti-angiogenic drugs, such as Sunitinib, bevacizumab, etc.; * Patients were taking immunosuppressants or systemic hormone therapy for immunosuppressive purposes (doses greater than 10mg/day prednisone or other equivalent hormones) and were still taking them within 2 weeks prior to enrollment; * The patient has any active autoimmune disease or a history of autoimmune disease; Have clinical symptoms or diseases of the heart that are not well controlled; * Congenital or acquired immune deficiency; * History of gastrointestinal perforation or open biopsy within 4 weeks prior to enrollment; ≥CTCAE grade 3 for any bleeding event, presence of unhealed wounds, ulcers, or fractures; * Hyperarterial/venous thrombosis events occurred within 6 months before the study period, such as non-cardiovascular and cerebrovascular events (including temporary ischemic attack), deep vein thrombosis (except venous thrombosis caused by intravenous catheterization during previous chemotherapy and cured by investigators), pulmonary embolism, etc.; Cardiac angioplasty or coronary bypass surgery for unstable arrhythmia, unstable angina pectoris or myocardial infarction; * People with active bleeding or bleeding tendency; * Correcting QT interval \> 480msec; If a patient has QT interval prolongation, but the cause of the prolongation is assessed by the investigator as a pacemaker (and no other cardiac abnormalities), the patient should be considered suitable for inclusion in the study after discussion with the sponsor study physician; * Patients suspected of having other primary cancers; Patients with other primary malignancies within the 5 years prior to the study (other than adequately treated cervical or skin cancer in situ, such as basal cell carcinoma, squamous cell carcinoma, or non-melanoma skin cancer); * Combined diseases/medical history: 1. Clinically significant hemoptysis (\> 50ml daily hemoptysis) occurred within 3 months prior to enrollment; Or clinically significant bleeding symptoms or definite bleeding tendencies, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, stool occult blood or above at baseline, or vasculitis; 2. hypertension, which is not well controlled by antihypertensive drugs (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100mmHg); In the 6 months prior to randomization, the following conditions had occurred: myocardial infarction, severe/unstable angina pectoris, NYHA grade 2 or higher cardiac dysfunction, clinically significant supracentricular or ventricular arrhythmias, and symptomatic congestive heart failure; 3. interstitial lung disease, non-infectious pneumonia or uncontrollable systemic diseases (such as poorly controlled diabetes (fasting blood glucose (FBG) \> 10mmol/ L), pulmonary fibrosis and acute pneumonia, etc.); Renal failure requires hemodialysis or peritoneal dialysis; Liver cirrhosis, decompensated liver disease, active hepatitis (hepatitis B, defined as HBV-DNA ≥ 500 IU/ml; Hepatitis C, defined as HCV-RNA above the lower detection limit of analytical methods) or chronic hepatitis requiring antiviral therapy; (6) Live attenuated vaccine vaccination history within 28 days prior to the first study or live attenuated vaccine vaccination expected during the study period; (7) Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS); Combined with hepatitis B and hepatitis C co-infection; Severe infection, including but not limited to bacteremia requiring hospitalization, severe pneumonia, etc. within 4 weeks before the first dose; Active infection of CTCAE grade ≥2 requiring systemic antibiotic treatment within 2 weeks prior to first administration, or unexplained fever \>38.5°C during screening/prior to first administration (fever due to tumor, as determined by the investigator, was eligible for inclusion); Evidence of active tuberculosis infection within 1 year prior to administration; Major surgery within 28 days prior to randomization (tissue biopsy required for diagnosis and insertion of a central venous catheter through peripheral venipentesis \[PICC\] or infusion PORT is permitted); * Participants who have previously received or are preparing to receive allogeneic bone marrow transplantation or solid organ transplantation; * Peripheral neuropathy ≥ grade 2; Patients with active brain metastases, malignant meningitis, spinal cord compression, or imaging CT or MRI findings of brain or pia disease during screening (patients with brain metastases who have completed treatment 14 days before enrollment and whose symptoms are stable can be enrolled, but only after brain MRI, CT or venography evaluation to confirm no symptoms of cerebral hemorrhage); * significant factors affecting oral drug absorption, such as inability to swallow, chronic diarrhea, and presence of clinically significant intestinal obstruction. * Women who are pregnant, breastfeeding, planning to become pregnant during the study period, or men or women who are fertile but do not want to use appropriate contraceptive methods. * The presence of other serious physical or mental illnesses or abnormalities in laboratory tests that may increase the risk of participating in the study or interfere with the study results, and patients who are deemed by the investigato * not suitable for participation in the study; * Patients with brain metastasis; * Imaging shows that the tumor has invaded important blood vessels, or follow-up shows that the tumor is highly likely to invade important blood vessels and cause fatal bleeding; * Drugs that interact with anlotinib hydrochloride capsules/piamplizumab are being used; **Maximum Age:** 75 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Fangjian Zhou, Doctor **Phone:** 13922735659 **Role:** CONTACT #### Locations **Location 1:** **City:** Guangzhou **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Kai Yao, M.D Ph.D - **Phone:** +8615913181211 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Shengjie Guo, M.D Ph.D - **Phone:** 13416140919 - **Role:** CONTACT ***Contact 3:*** - **Name:** Kai Yao, M.D Ph.D - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 4:*** - **Name:** Shengjie Guo, M.D Ph.D - **Role:** PRINCIPAL_INVESTIGATOR **Country:** China **Facility:** Cancer Center, Sun Yat-sen University **State:** Guangdong **Status:** RECRUITING **Zip:** 510060 #### Overall Officials **Official 1:** **Affiliation:** Sun Yat-sen University **Name:** Shengjie Guo, Doctor **Role:** STUDY_CHAIR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010235 - Term: Paraganglioma - ID: D000018358 - Term: Neuroendocrine Tumors - ID: D000017599 - Term: Neuroectodermal Tumors - ID: D000009373 - Term: Neoplasms, Germ Cell and Embryonal - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000009380 - Term: Neoplasms, Nerve Tissue ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M13578 - Name: Pheochromocytoma - Relevance: HIGH - As Found: Pheochromocytoma - ID: M13149 - Name: Paraganglioma - Relevance: LOW - As Found: Unknown - ID: M20495 - Name: Neuroendocrine Tumors - Relevance: LOW - As Found: Unknown - ID: M19845 - Name: Neuroectodermal Tumors - Relevance: LOW - As Found: Unknown - ID: M20388 - Name: Neuroectodermal Tumors, Primitive - Relevance: LOW - As Found: Unknown - ID: M12318 - Name: Neoplasms, Germ Cell and Embryonal - Relevance: LOW - As Found: Unknown - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M12325 - Name: Neoplasms, Nerve Tissue - Relevance: LOW - As Found: Unknown - ID: T4530 - Name: Pheochromocytoma - Relevance: HIGH - As Found: Pheochromocytoma - ID: T4409 - Name: Paragangliomas 1 - Relevance: LOW - As Found: Unknown - ID: T4091 - Name: Neuroendocrine Tumor - Relevance: LOW - As Found: Unknown - ID: T4092 - Name: Neuroepithelioma - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000010673 - Term: Pheochromocytoma ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429384 **Brief Title:** Y-3 Injection in the Treatment of Acute Ischemic Stroke Phase II Clinical Trial **Official Title:** Y-3 Injection in the Treatment of Acute Ischemic Stroke Phase II Clinical Trial -- Multicenter, Randomized, Double-blind, Parallel, Placebo-controlled Phase II Clinical Trial #### Organization Study ID Info **ID:** Y-3-LC-02 #### Organization **Class:** OTHER **Full Name:** Beijing Tiantan Hospital ### Status Module #### Completion Date **Date:** 2023-12-24 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-06-04 **Type:** ACTUAL **Last Update Submit Date:** 2024-06-03 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2023-11-18 **Type:** ACTUAL #### Start Date **Date:** 2023-06-04 **Type:** ACTUAL **Status Verified Date:** 2024-06 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-04-03 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** NeuroDawn Pharmaceutical Co., Ltd. #### Lead Sponsor **Class:** OTHER **Name:** Beijing Tiantan Hospital #### Responsible Party **Investigator Affiliation:** Beijing Tiantan Hospital **Investigator Full Name:** Yongjun Wang **Investigator Title:** Chief Physician **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The objective of this clinical trial was to explore the efficacy and safety of Y-3 injection at different doses in patients with acute ischemic stroke within 48 hours of onset. A multicenter, randomized, double-blind, parallel, placebo-controlled trial design was designed to include 240 participants. Subjects press 1:1:1: 1 ratio of patients were randomly divided into Y-3 low-dose group (20 mg/ time, qd), medium-dose group (40 mg/ time, qd), high-dose group (60mg/ time, qd) and placebo control group, with 60 cases in each group. Random stratification factors include: Time of onset (≤24 hours, \&gt; 24 hours). The patients were treated for 10 consecutive days (10 times) and followed up to 90 days after the first dose. The trial was divided into three phases: screening/baseline, treatment, and follow-up. Screening/baseline period: Subjects enter the screening/baseline period for screening examination after signing the informed consent. Treatment period: Eligible subjects were randomly assigned at a ratio of 1:1:1:1 to receive Y-3 injection low-dose group, medium-dose group, high-dose group and placebo control drug for 10 consecutive days (10 times), during which relevant examinations required by the protocol were conducted and safety was assessed. Follow-up period: Participants who finished treatment were followed up until 90 days after the first dose. Stroke-related scale scores were performed at 10, 30, and 90 days after first use of the investigational drug The scores of Montgomery Depression Rating Scale (MSAS) and Hamilton Anxiety Scale (HAMA) were performed on the 10th and 90th days after the use of experimental drugs. Adverse events were recorded during treatment and follow-up to further assess safety **Detailed Description:** A multicenter, randomized, double-blind, parallel, placebo-controlled trial design was designed to include 240 participants, who were randomly assigned to Y-3 low-dose group (20 mg/ time, qd), medium-dose group (40 mg/ time, qd), high-dose group (60 mg/ time, qd) and placebo control group in a ratio of 1:1:1:1. Each group had 60 cases. Random stratification factors included: onset time (≤24 hours, \> 24 hours).The patients were treated for 10 consecutive days (10 times) and followed up to 90 days after the first dose. The trial was divided into three phases:screening/baseline, treatment, and follow-up. Screening/baseline period: Subjects enter the screening/baseline period for screening examination after signing the informed consent.Treatment period: Eligible subjects were randomly assigned at a ratio of 1:1:1:1 to receive Y-3 injection low-dose group, medium-dose group, high-dose group and placebo control drug for 10 consecutive days (10 times), during which relevant examinations required by the protocol were conducted and safety was assessed.Follow-up period: Participants who finished treatment were followed up until 90 days after the first dose.Stroke-related scale scores were performed on the 10th, 30th and 90th days after the first use of the experimental drug, and Montgomery Depression Rating Scale (MADRS) and Hamilton Anxiety Scale (HAMA) scores were performed on the 10th and 90th days after the first use of the experimental drug. Adverse events were recorded during treatment and follow-up to further assess safety. ### Conditions Module **Conditions:** - Acute Ischemic Stroke ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Y-3 low dose group (20 mg/ time, qd), medium dose group (40 mg/ time qd), high dose group (60mg/ time, qd) and placebo control group. ##### Masking Info **Masking:** QUADRUPLE **Masking Description:** In a double-blind design, the researchers, the researchers involved in the trial effect evaluation, the data managers, the statistical analysts, and the subjects and their relatives or guardians were blind to the treatment groups. **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 240 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Y-3 injection 20mg diluted with about 250 ml normal saline, intravenous infusion, qd, continuous medication for 10 days. **Intervention Names:** - Drug: Y-3 Injection/Y-3 blank injection **Label:** Y-3 low-dose group (20 mg/dose, qd) **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Y-3 injection 40mg diluted with about 250 ml normal saline, intravenous infusion, qd, continuous medication for 10 days. **Intervention Names:** - Drug: Y-3 Injection/Y-3 blank injection **Label:** Y-3 medium dose group (40 mg/dose, qd) **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Y-3 injection 60mg diluted with about 250 ml normal saline, intravenous infusion, qd, continuous medication for 10 days. **Intervention Names:** - Drug: Y-3 Injection/Y-3 blank injection **Label:** Y-3 high-dose group (60 mg/dose, qd) **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** Y-3 blank injection 10ml was diluted with about 250 ml normal saline, intravenous infusion, qd, and continuous medication for 10 days. **Intervention Names:** - Drug: Y-3 Injection/Y-3 blank injection **Label:** Blank control group **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Blank control group - Y-3 high-dose group (60 mg/dose, qd) - Y-3 low-dose group (20 mg/dose, qd) - Y-3 medium dose group (40 mg/dose, qd) **Description:** The first dose should be completed as soon as possible after randomization; The time from the second dose to the first dose shall not be less than 12h, but not more than 24h+1h; The time interval of each subsequent administration is 24h±1h; **Name:** Y-3 Injection/Y-3 blank injection **Type:** DRUG ### Outcomes Module #### Other Outcomes **Description:** Montgomery Depression Rating Scale scores on day 10 and day 90 were \&lt, respectively; Proportion of patients with scores of 12, ≥12, and ≥22.There are 10 items in the scale, with a total score of 60 points. The higher the score, the higher the degree of depression. MADRS \< 12 indicates no depressive symptoms, 12≤MADRS \< 22 indicates mild depression, 22≤MADRS \< 30 indicates moderate depression, and MADRS≥30 indicates severe depression. **Measure:** Montgomery Depression Rating Scale scores on day 10 and day 90 were &lt, respectively; Proportion of patients with scores of 12, ≥12, and ≥22; **Time Frame:** On the 10th and 90th day of treatment **Description:** Hamilton Anxiety Scale (HAMA) scores on day 10 and day 90 were \&lt, respectively; Proportion of patients with scores of 7, ≥7, and ≥14.The scale used a 5-level scoring method, and the criteria for each level were: 0-asymptomatic; 1- Light; 2- Medium; 3- heavy; 4- Extremely heavy. The total score of Hamilton anxiety Scale is a very important basis to reflect the severity of patients' anxiety, that is, the less severe the disease, the lower the total score; The more severe the condition, the higher the total score. A total score of less than 7 is considered to have no symptoms of anxiety; A score of 7-13 is considered to be likely to have anxiety; A score of 14 to 20 is considered to be definitely anxious; 21 to 28 points, is considered to have significant anxiety; A score greater than 29 is considered likely to be severe anxiety. **Measure:** Hamilton Anxiety Scale scores on day 10 and day 90 were &lt, respectively; Proportion of patients with scores of 7, ≥7, and ≥14. **Time Frame:** On the 10th and 90th day of treatment **Description:** Incidence of adverse events (AE) in each group; **Measure:** Incidence of adverse events (AE) in each group; **Time Frame:** From the time the subject receives medication to the end of the 90th day of the treatment **Description:** The incidence of treatment-related adverse events (TEAEs) in each group; **Measure:** The incidence of treatment-related adverse events (TEAEs) in each group; **Time Frame:** From the time the subject receives medication to the end of the 90th day of the treatment **Description:** The occurrence of important adverse events in each group; **Measure:** The occurrence of important adverse events in each group; **Time Frame:** From the time the subject receives medication to the end of the 90th day of the treatment **Description:** The occurrence of serious adverse events (SAEs) in each group; **Measure:** The occurrence of serious adverse events (SAEs) in each group; **Time Frame:** From the time the subject receives medication to the end of the 90th day of the treatment **Description:** The occurrence of suspicious and unexpected serious adverse reactions (SUSAR) in each group; **Measure:** The occurrence of suspicious and unexpected serious adverse reactions (SUSAR) in each group; **Time Frame:** From the time the subject receives medication to the end of the 90th day of the treatment **Description:** Detect blood routine through a blood cell analyzer, including white blood cell count, neutrophil count, lymphocyte count, hemoglobin, and platelet count.Use a biochemical analyzer to detect blood biochemistry, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, direct bilirubin, creatinine, urea/urea nitrogen, uric acid, and so on. Detect coagulation function through a coagulation analyzer, including prothrombin time (PT), partially activated prothrombin time (APTT), international standardized ratio (INR), fibrinogen (FIB).Detect urine routine through a urine analyzer.These indicators are measured during the baseline period and post administration visit period to observe the impact of the drug on this indicator, whether the drug will cause AE and SAE，the occurrence of AE and SAE, the type and severity of AE and SAE, and ultimately to determine the safety of the drug. **Measure:** Laboratory examination indicators: blood routine, urine routine, blood biochemistry, Laboratory examination indicators: blood routine, urine routine, blood biochemistry, coagulation function **Time Frame:** Baseline period, on the 10th , 30th and 90th day **Description:** Detecting parameters such as heart rate, electrocardiogram, and QT interval through an electrocardiogram monitor.Detecting blood pressure through a blood pressure monitor.Detecting body temperature through a thermometer.Detect respiratory rate by observing changes in chest contour count of the subject.These indicators are measured during the baseline period and post administration visit period to observe the impact of the drug on this indicator, whether the drug will cause AE and SAE，the occurrence of AE and SAE, the type and severity of AE and SAE, and ultimately to determine the safety of the drug. **Measure:** Vital signs: heart rate, blood pressure, body temperature, respiration **Time Frame:** Baseline period, on the 10th , 30th and 90th day **Description:** Detect systems such as lungs, gastrointestinal tract, urinary system, musculoskeletal, skin, lymph nodes, etc. through observation, auscultation, percussion, palpation, and other examination methods. These indicators are measured during the baseline period and post administration visit period to observe the impact of the drug on this indicator, whether the drug will cause AE and SAE，the occurrence of AE and SAE, the type and severity of AE and SAE, and ultimately to determine the safety of the drug. **Measure:** Physical examination of the whole body: lungs, gastrointestinal tract, urinary system, musculoskeletal system, skin, lymph nodes, and other systems. **Time Frame:** Baseline period, on the 10th , 30th and 90th day **Description:** Laboratory evaluation not specified in the protocol, including parameters such as hematology, biochemical tests, urine analysis, etc. These indicators are measured during the baseline period and post administration visit period to observe the impact of the drug on this indicator, whether the drug will cause AE and SAE，the occurrence of AE and SAE, the type and severity of AE and SAE, and ultimately to determine the safety of the drug. **Measure:** Clinical laboratory examination **Time Frame:** From the baseline period to the end of the 90th day of the treatment **Description:** Discontinuation due to adverse events【AE includes abnormal laboratory test results (haematological, clinical biochemical, or urinalysis) or other safety assessments (e.g. electrocardiograms, radiological scans, vital signs measurements), including deterioration relative to baseline and deemed clinically significant in the medical and scientific judgment of the investigator; Exacerbation of pre-existing diseases; A new condition detected or diagnosed after the initiation of the investigational drug.】 **Measure:** Discontinuation due to adverse events; **Time Frame:** From the beginning to the end caused by adverse events **Description:** Discontinuation due to any other non-adverse event(Any discontinuation other than an adverse event) **Measure:** Discontinuation due to any other non-adverse event. **Time Frame:** From the beginning to the end due to unexpected circumstances except for adverse events #### Primary Outcomes **Description:** The proportion of subjects with mRS score ≤ 1 on the 90th day of treatment . **Measure:** The proportion of subjects with mRS score ≤ 1 on the 90th day of treatment . **Time Frame:** 90th day of treatment #### Secondary Outcomes **Description:** Grade analysis of mRS Score on the 90th day of treatment; **Measure:** Grade analysis of mRS Score on the 90th day of treatment; **Time Frame:** 90th day of treatment **Description:** The proportion of subjects with mRS Score ≤2 on the 90th day of treatment; **Measure:** The proportion of subjects with mRS Score ≤2 on the 90th day of treatment; **Time Frame:** 90th day of treatment **Description:** Changes in NIH Stroke Scale from baseline on day 10 of treatment; **Measure:** Changes in NIH Stroke Scale from baseline on day 10 of treatment; **Time Frame:** 10th day of treatment **Description:** Proportion of NIH Stroke of 0-1 or ≥4 reduction from baseline on day 10 and day 30 of treatment.The content of NIHSS score included: consciousness level (consciousness level, consciousness level questioning, consciousness level command), gaze, visual field, facial paralysis, upper limb movement, lower limb movement, body aid movement, sensation, language, dysarthria, neglect. The score ranges from 0 to 42, with higher scores indicating more severe nerve damage.Score 0 to 1: normal or nearly normal Scores 1-4: mild stroke/minor stroke .5 to 15 points: moderate stroke .15-20 points: moderate to severe stroke Scores 21-42: severe stroke **Measure:** Proportion of NIH Stroke of 0-1 or ≥4 reduction from baseline on day 10 and day 30 of treatment. **Time Frame:** On the 10th and 30th day of treatment ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: - Only those who meet all the following criteria can be included in the group: 1. Age ≥ 18 years old and\<81 years old, regardless of gender; 2. After the onset of this disease, the National Institutes of Research Stroke Scale score was 6 ≤ NIHSS ≤ 20 points, and the sum of the 5th upper limb and 6th lower limb scores was ≥ 2 points. If patients receiving thrombolysis treatment were screened and evaluated based on the NIHSS score after thrombolysis; 3. Within 48 hours (including 48 hours) of onset; 4. Diagnosed as ischemic stroke according to the "Key Diagnostic Points for Various Major Cerebrovascular Diseases in China 2019", with good recovery after the first or last onset (mRS score ≤ 1 point before this onset); 5. Obtain informed consent from the patient or their legal representative voluntarily signed and approved by the ethics committee. Exclusion Criteria: - Those who meet one of the following criteria during filtering cannot be included in the group: 1. Intracranial hemorrhagic diseases seen on cranial imaging: hemorrhagic stroke, epidural hematoma, intracranial hematoma, ventricular hemorrhage, subarachnoid hemorrhage, etc; If it is only oozing blood, the researcher can determine whether it is suitable for enrollment; 2. Severe consciousness disorder: The item score of NIHSS's 1a consciousness level is greater than 1 point; 3. Transient ischemic attack (TIA); 4. After controlling the patient's blood pressure, the systolic blood pressure remains ≥ 220mmHg or the diastolic blood pressure remains ≥ 120mmHg; 5. Previously diagnosed patients with severe mental disorders and severe dementia; 6. Patients previously diagnosed with depression or anxiety disorder; 7. Patients undergoing antidepressant or anti anxiety treatment; 8. Diagnosed with severe active liver diseases, such as acute hepatitis, chronic active hepatitis, liver cirrhosis, etc; Or ALT or AST\>2.0 × ULN; 9. Diagnosed with severe active kidney disease or renal insufficiency; Or serum creatinine\>1.5 × ULN; 10. After the onset of the disease, drugs with brain cytoprotection in the instructions have been used, such as edaravone, concentrated solution of edaravone and dextranol for injection, nimodipine, ganglioside, CDPC, piracetam, oxiracetam, butylphenylpeptide, human urinary kallidinogenase (Urinary Kallidinogenase), cinepazide, rat nerve growth factor, cerebrolysin (cerebroprotein hydrolysate), calf serum deproteinized injection Calf blood deproteinized extract injection, etc; 11. After the onset of this disease, thrombectomy or interventional therapy has been applied or planned to be applied; 12. Previously diagnosed with concurrent malignant tumors and undergoing anti-tumor treatment; 13. Previously diagnosed with severe systemic diseases, with an estimated survival period of\<90 days; 14. The patient is in pregnancy, lactation, and there is a possibility of pregnancy in the patient/patient partner who plans to conceive during the trial period; 15. Previously known allergies to this product or any of its excipients (15-hydroxystearic acid polyethylene glycol ester, propylene glycol, sodium hydroxide); 16. A history of major surgeries within 4 weeks prior to enrollment and assessed by the researcher as affecting neurological function scores or affecting 90 day survival; 17. Have participated in other clinical studies or are currently participating in other clinical studies within the first 30 days of randomization; 18. The researcher believes that it is not suitable to participate in this clinical study. **Maximum Age:** 80 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Beijing **Country:** China **Facility:** Beijing Tiantan Hospital, Capital Medical University Beijing **State:** Beijing **Zip:** 100000 **Location 2:** **City:** Liuzhou **Country:** China **Facility:** Liuzhou Workers Hospital **State:** Guangxi **Zip:** 545000 **Location 3:** **City:** Cangzhou **Country:** China **Facility:** Cangzhou Central Hospital **State:** Hebei **Zip:** 061000 **Location 4:** **City:** Hengshui **Country:** China **Facility:** Harrison International Peace Hospital **State:** Hebei **Zip:** 053000 **Location 5:** **City:** Daqing **Country:** China **Facility:** Daqing Oilfield General Hospital **State:** Heilongjiang **Zip:** 163000 **Location 6:** **City:** Daqing **Country:** China **Facility:** Daqing People's Hospital **State:** Heilongjiang **Zip:** 163000 **Location 7:** **City:** Nanyang **Country:** China **Facility:** Nanyang Second People's Hospital **State:** Henan **Zip:** 473000 **Location 8:** **City:** Nanyang **Country:** China **Facility:** Nanyang South Stone Hospital **State:** Henan **Zip:** 473000 **Location 9:** **City:** Nanyang **Country:** China **Facility:** The First Affiliated Hospital of Nanyang Medical College **State:** Henan **Zip:** 473000 **Location 10:** **City:** Changsha **Country:** China **Facility:** Hunan Provincial People's Hospital **State:** Hunan **Zip:** 410000 **Location 11:** **City:** Baotou **Country:** China **Facility:** The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology **State:** Inner Mongolia Autonomous Region **Zip:** 014000 **Location 12:** **City:** Baotou **Country:** China **Facility:** Inner Mongolia Baotou Steel Hospital **State:** Inner Mongolia Autonomous Region **Zip:** 014100 **Location 13:** **City:** Hohhot **Country:** China **Facility:** Inner Mongolia International Mongolian Medicine Hospital **State:** Inner Mongolia Autonomous Region **Zip:** 010000 **Location 14:** **City:** Huai'an **Country:** China **Facility:** Huai 'an First People's Hospital **State:** Jiangsu **Zip:** 223001 **Location 15:** **City:** Lianyungang **Country:** China **Facility:** Lianyungang First People's Hospital **State:** Jiangsu **Zip:** 222000 **Location 16:** **City:** Lianyungang **Country:** China **Facility:** Lianyungang Second People's Hospital **State:** Jiangsu **Zip:** 222000 **Location 17:** **City:** Taizhou **Country:** China **Facility:** Taizhou Second People's Hospital **State:** Jiangsu **Zip:** 225300 **Location 18:** **City:** Xuzhou **Country:** China **Facility:** Xuzhou Central Hospital (Old Hospital Area) **State:** Jiangsu **Zip:** 221000 **Location 19:** **City:** Xuzhou **Country:** China **Facility:** Xuzhou Central Hospital（New compound） **State:** Jiangsu **Zip:** 221000 **Location 20:** **City:** Xuzhou **Country:** China **Facility:** Xuzhou First People's Hospital **State:** Jiangsu **Zip:** 221000 **Location 21:** **City:** Pingxiang **Country:** China **Facility:** Pingxiang People's Hospital **State:** Jiangxi **Zip:** 337000 **Location 22:** **City:** Beipiao **Country:** China **Facility:** Beipiao Central Hospital **State:** Liaoning **Zip:** 122100 **Location 23:** **City:** Jinzhou **Country:** China **Facility:** The First Affiliated Hospital of Jinzhou Medical University **State:** Liaoning **Zip:** 121000 **Location 24:** **City:** Shenyang **Country:** China **Facility:** Chinese People's Liberation Army Northern Theater Command General Hospital **State:** Liaoning **Zip:** 110000 **Location 25:** **City:** Shenyang **Country:** China **Facility:** Shenyang First People's Hospital **State:** Liaoning **Zip:** 110000 **Location 26:** **City:** Jinan **Country:** China **Facility:** Shandong Third Hospital **State:** Shandong **Zip:** 250000 **Location 27:** **City:** Liaocheng **Country:** China **Facility:** Liaocheng People's Hospital **State:** Shandong **Zip:** 252000 **Location 28:** **City:** Linyi **Country:** China **Facility:** Tancheng County First People's Hospital **State:** Shandong **Zip:** 276100 **Location 29:** **City:** Tengzhou **Country:** China **Facility:** Tengzhou Central People's Hospital **State:** Shandong **Zip:** 277500 **Location 30:** **City:** Dongyang **Country:** China **Facility:** Dongyang City People's Hospital **State:** Zhejiang **Zip:** 322100 #### Overall Officials **Official 1:** **Affiliation:** IRB of Beijing Tiantan Hospital Capital Medical University Beijing **Name:** Shuya Li **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Smith WS, Lev MH, English JD, Camargo EC, Chou M, Johnston SC, Gonzalez G, Schaefer PW, Dillon WP, Koroshetz WJ, Furie KL. Significance of large vessel intracranial occlusion causing acute ischemic stroke and TIA. Stroke. 2009 Dec;40(12):3834-40. doi: 10.1161/STROKEAHA.109.561787. Epub 2009 Oct 15. **PMID:** 19834014 **Citation:** Emberson J, Lees KR, Lyden P, Blackwell L, Albers G, Bluhmki E, Brott T, Cohen G, Davis S, Donnan G, Grotta J, Howard G, Kaste M, Koga M, von Kummer R, Lansberg M, Lindley RI, Murray G, Olivot JM, Parsons M, Tilley B, Toni D, Toyoda K, Wahlgren N, Wardlaw J, Whiteley W, del Zoppo GJ, Baigent C, Sandercock P, Hacke W; Stroke Thrombolysis Trialists' Collaborative Group. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet. 2014 Nov 29;384(9958):1929-35. doi: 10.1016/S0140-6736(14)60584-5. Epub 2014 Aug 5. **PMID:** 25106063 **Citation:** Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC, Kidwell CS, Leslie-Mazwi TM, Ovbiagele B, Scott PA, Sheth KN, Southerland AM, Summers DV, Tirschwell DL. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2019 Dec;50(12):e344-e418. doi: 10.1161/STR.0000000000000211. Epub 2019 Oct 30. Erratum In: Stroke. 2019 Dec;50(12):e440-e441. **PMID:** 31662037 **Citation:** Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC, Kidwell CS, Leslie-Mazwi TM, Ovbiagele B, Scott PA, Sheth KN, Southerland AM, Summers DV, Tirschwell DL; American Heart Association Stroke Council. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2018 Mar;49(3):e46-e110. doi: 10.1161/STR.0000000000000158. Epub 2018 Jan 24. Erratum In: Stroke. 2018 Mar;49(3):e138. Stroke. 2018 Apr 18;: **PMID:** 29367334 **Citation:** van Horn N, Kniep H, Leischner H, McDonough R, Deb-Chatterji M, Broocks G, Thomalla G, Brekenfeld C, Fiehler J, Hanning U, Flottmann F. Predictors of poor clinical outcome despite complete reperfusion in acute ischemic stroke patients. J Neurointerv Surg. 2021 Jan;13(1):14-18. doi: 10.1136/neurintsurg-2020-015889. Epub 2020 May 15. **PMID:** 32414889 **Citation:** Lee SH, Kim BJ, Han MK, Park TH, Lee KB, Lee BC, Yu KH, Oh MS, Cha JK, Kim DH, Nah HW, Lee J, Lee SJ, Kim JG, Park JM, Kang K, Cho YJ, Hong KS, Park HK, Choi JC, Kim JT, Choi K, Kim DE, Ryu WS, Kim WJ, Shin DI, Yeo M, Sohn SI, Hong JH, Lee J, Lee JS, Khatri P, Bae HJ. Futile reperfusion and predicted therapeutic benefits after successful endovascular treatment according to initial stroke severity. BMC Neurol. 2019 Jan 15;19(1):11. doi: 10.1186/s12883-019-1237-2. **PMID:** 30646858 **Citation:** Meyer L, Alexandrou M, Leischner H, Flottmann F, Deb-Chatterji M, Abdullayev N, Maus V, Politi M, Roth C, Kastrup A, Thomalla G, Mpotsaris A, Fiehler J, Papanagiotou P. Mechanical thrombectomy in nonagenarians with acute ischemic stroke. J Neurointerv Surg. 2019 Nov;11(11):1091-1094. doi: 10.1136/neurintsurg-2019-014785. Epub 2019 Apr 27. **PMID:** 31030188 **Citation:** Chamorro A, Lo EH, Renu A, van Leyen K, Lyden PD. The future of neuroprotection in stroke. J Neurol Neurosurg Psychiatry. 2021 Feb;92(2):129-135. doi: 10.1136/jnnp-2020-324283. Epub 2020 Nov 4. **PMID:** 33148815 **Citation:** Li J, Zhang L, Xu C, Shen YY, Lin YH, Zhang Y, Wu HY, Chang L, Zhang YD, Chen R, Zhang ZP, Luo CX, Li F, Zhu DY. A pain killer without analgesic tolerance designed by co-targeting PSD-95-nNOS interaction and alpha2-containning GABAARs. Theranostics. 2021 Apr 3;11(12):5970-5985. doi: 10.7150/thno.58364. eCollection 2021. **PMID:** 33897893 **Citation:** Li J, Zhang L, Xu C, Lin YH, Zhang Y, Wu HY, Chang L, Zhang YD, Luo CX, Li F, Zhu DY. Prolonged Use of NMDAR Antagonist Develops Analgesic Tolerance in Neuropathic Pain via Nitric Oxide Reduction-Induced GABAergic Disinhibition. Neurotherapeutics. 2020 Jul;17(3):1016-1030. doi: 10.1007/s13311-020-00883-w. **PMID:** 32632774 **Citation:** Kaur H, Prakash A, Medhi B. Drug therapy in stroke: from preclinical to clinical studies. Pharmacology. 2013;92(5-6):324-34. doi: 10.1159/000356320. Epub 2013 Dec 12. **PMID:** 24356194 **Citation:** Fisher M; Stroke Therapy Academic Industry Roundtable. Recommendations for advancing development of acute stroke therapies: Stroke Therapy Academic Industry Roundtable 3. Stroke. 2003 Jun;34(6):1539-46. doi: 10.1161/01.STR.0000072983.64326.53. Epub 2003 May 15. **PMID:** 12750546 **Citation:** Hackett ML, Kohler S, O'Brien JT, Mead GE. Neuropsychiatric outcomes of stroke. Lancet Neurol. 2014 May;13(5):525-34. doi: 10.1016/S1474-4422(14)70016-X. Epub 2014 Mar 28. **PMID:** 24685278 **Citation:** Ferro JM, Caeiro L, Figueira ML. Neuropsychiatric sequelae of stroke. Nat Rev Neurol. 2016 May;12(5):269-80. doi: 10.1038/nrneurol.2016.46. Epub 2016 Apr 11. **PMID:** 27063107 **Citation:** Murrough JW, Abdallah CG, Mathew SJ. Targeting glutamate signalling in depression: progress and prospects. Nat Rev Drug Discov. 2017 Jul;16(7):472-486. doi: 10.1038/nrd.2017.16. Epub 2017 Mar 17. **PMID:** 28303025 **Citation:** Luscher B, Shen Q, Sahir N. The GABAergic deficit hypothesis of major depressive disorder. Mol Psychiatry. 2011 Apr;16(4):383-406. doi: 10.1038/mp.2010.120. Epub 2010 Nov 16. **PMID:** 21079608 **Citation:** Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell. 2009 Oct 16;139(2):267-84. doi: 10.1016/j.cell.2009.09.028. **PMID:** 19837031 **Citation:** Griebel G, Holmes A. 50 years of hurdles and hope in anxiolytic drug discovery. Nat Rev Drug Discov. 2013 Sep;12(9):667-87. doi: 10.1038/nrd4075. **PMID:** 23989795 **Citation:** Shabel SJ, Proulx CD, Piriz J, Malinow R. Mood regulation. GABA/glutamate co-release controls habenula output and is modified by antidepressant treatment. Science. 2014 Sep 19;345(6203):1494-8. doi: 10.1126/science.1250469. Epub 2014 Sep 18. **PMID:** 25237099 **Citation:** Li YF. A hypothesis of monoamine (5-HT) - Glutamate/GABA long neural circuit: Aiming for fast-onset antidepressant discovery. Pharmacol Ther. 2020 Apr;208:107494. doi: 10.1016/j.pharmthera.2020.107494. Epub 2020 Jan 25. **PMID:** 31991195 **Citation:** Gould TD, Zarate CA Jr, Thompson SM. Molecular Pharmacology and Neurobiology of Rapid-Acting Antidepressants. Annu Rev Pharmacol Toxicol. 2019 Jan 6;59:213-236. doi: 10.1146/annurev-pharmtox-010617-052811. Epub 2018 Oct 8. **PMID:** 30296896 **Citation:** Zhou L, Li F, Xu HB, Luo CX, Wu HY, Zhu MM, Lu W, Ji X, Zhou QG, Zhu DY. Treatment of cerebral ischemia by disrupting ischemia-induced interaction of nNOS with PSD-95. Nat Med. 2010 Dec;16(12):1439-43. doi: 10.1038/nm.2245. Epub 2010 Nov 21. Erratum In: Nat Med. 2011 Sep;17(9):1153. **PMID:** 21102461 **Citation:** Luo CX, Lin YH, Qian XD, Tang Y, Zhou HH, Jin X, Ni HY, Zhang FY, Qin C, Li F, Zhang Y, Wu HY, Chang L, Zhu DY. Interaction of nNOS with PSD-95 negatively controls regenerative repair after stroke. J Neurosci. 2014 Oct 1;34(40):13535-48. doi: 10.1523/JNEUROSCI.1305-14.2014. **PMID:** 25274829 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000002561 - Term: Cerebrovascular Disorders - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000010335 - Term: Pathologic Processes - ID: D000020520 - Term: Brain Infarction - ID: D000002545 - Term: Brain Ischemia - ID: D000007238 - Term: Infarction - ID: D000009336 - Term: Necrosis ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10543 - Name: Ischemia - Relevance: HIGH - As Found: Ischemic - ID: M22306 - Name: Stroke - Relevance: HIGH - As Found: Stroke - ID: M2400 - Name: Ischemic Stroke - Relevance: HIGH - As Found: Ischemic Stroke - ID: M5793 - Name: Cerebral Infarction - Relevance: HIGH - As Found: Ischemic Stroke - ID: M10282 - Name: Infarction - Relevance: LOW - As Found: Unknown - ID: M5810 - Name: Cerebrovascular Disorders - Relevance: LOW - As Found: Unknown - ID: M5204 - Name: Brain Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: M22305 - Name: Brain Infarction - Relevance: LOW - As Found: Unknown - ID: M5794 - Name: Brain Ischemia - Relevance: LOW - As Found: Unknown - ID: M12284 - Name: Necrosis - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000020521 - Term: Stroke - ID: D000083242 - Term: Ischemic Stroke - ID: D000002544 - Term: Cerebral Infarction - ID: D000007511 - Term: Ischemia ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429371 **Brief Title:** Biopsychosocial Contributors to Irritability in Individuals With Shoulder Pain **Official Title:** Biopsychosocial Contributors to Irritability in Individuals With Shoulder Pain #### Organization Study ID Info **ID:** 8 #### Organization **Class:** OTHER **Full Name:** University of Central Florida ### Status Module #### Completion Date **Date:** 2026-12-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-06-05 **Type:** ACTUAL **Last Update Submit Date:** 2024-06-03 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2026-12-01 **Type:** ESTIMATED #### Start Date **Date:** 2024-05-24 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-04-29 **Study First Submit QC Date:** 2024-05-23 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** University of Florida #### Lead Sponsor **Class:** OTHER **Name:** University of Central Florida #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Irritability was defined by Geoffrey Maitland as the vigor of activity to provoke symptoms, the severity of symptoms, and time for symptoms to subside. Irritability is deeply embedded in the physical therapy clinical decision-making process. However, the mechanisms contributing to irritability are unknown. Therefore, the purpose of this study is to characterize pain sensitivity and pain-related psychological factors by irritability level in individuals with shoulder pain. ### Conditions Module **Conditions:** - Shoulder Pain ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** CROSS_SECTIONAL #### Enrollment Info **Count:** 60 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Individuals with shoulder pain that is at least 3/10 within the past 24 hours. **Intervention Names:** - Other: Quantitative Sensory Testing - Other: Pain-Related Psychological Factors **Label:** Individuals with Shoulder Pain ### Interventions #### Intervention 1 **Arm Group Labels:** - Individuals with Shoulder Pain **Description:** Participants will undergo heat pain threshold, cold pain threshold, pressure pain threshold, temporal summation, and conditioned pain modulation to characterize pain sensitivity. **Name:** Quantitative Sensory Testing **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - Individuals with Shoulder Pain **Description:** Participants will complete psychological questionnaires to characterize these factors. **Name:** Pain-Related Psychological Factors **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** A thermode will be applied to the deltoid, tibialis anterior, and lower back. The thermode will gradually increase temperature until the sensation changes from comfortable warmth to pain (pain threshold). Once pain threshold is reached, the temperature in degrees Celsius for heat pain threshold is recorded. **Measure:** Heat pain Threshold **Time Frame:** Day 1 **Description:** A thermode will be applied to the deltoid, tibialis anterior, and lower back. The thermode will gradually decrease temperature until the sensation changes from comfortable cold to pain (pain threshold). Once pain threshold is reached, the temperature in degrees Celsius for cold pain threshold is recorded. **Measure:** Cold Pain Threshold **Time Frame:** Day 1 **Description:** An algometer will be applied to the deltoid, tibialis anterior, and lower back. Pressure will be gradually applied until the sensation changes from comfortable pressure to pain (pain threshold). Once pain threshold is reached, the pressure in kilopascals will be recorded for pressure pain threshold. **Measure:** Pressure Pain Threshold **Time Frame:** Day 1 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * shoulder pain symptom intensity rated as 3/10 or higher in the past 24 hours * attending physical therapy for shoulder pain Exclusion Criteria: * non-English speaking * systemic medical conditions that affect sensation, such as uncontrolled diabetes * history of shoulder surgery or fracture within the past 6 months * history of a chronic pain condition, such as fibromyalgia * blood clotting disorder, such as hemophilia * contraindication to the application of ice (blood pressure \> 140/90 mmHg, cold urticaria, cryoglobulinemia, paroxysmal cold hemoglobinuria, circulatory compromise) * currently pregnant **Maximum Age:** 75 Years **Minimum Age:** 18 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Individuals with shoulder pain ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Abigail W Anderson **Phone:** 4078231026 **Role:** CONTACT #### Locations **Location 1:** **City:** Orlando **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Abigail Wilson - **Role:** CONTACT **Country:** United States **Facility:** University of Central Florida **State:** Florida **Status:** RECRUITING **Zip:** 32765 #### Overall Officials **Official 1:** **Affiliation:** University of Central Florida **Name:** Abigail Anderson **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ## Derived Section ### Condition Browse Module - Ancestors - ID: D000018771 - Term: Arthralgia - ID: D000007592 - Term: Joint Diseases - ID: D000009140 - Term: Musculoskeletal Diseases - ID: D000010146 - Term: Pain - ID: D000009461 - Term: Neurologic Manifestations ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: BC10 - Name: Nervous System Diseases ### Condition Browse Module - Browse Leaves - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M21907 - Name: Shoulder Pain - Relevance: HIGH - As Found: Shoulder Pain - ID: M20833 - Name: Arthralgia - Relevance: LOW - As Found: Unknown - ID: M10621 - Name: Joint Diseases - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000020069 - Term: Shoulder Pain ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429358 **Brief Title:** The Role of Probiotics in Preventing Recurrent Urinary Tract Infections in Pregnant Women **Official Title:** The Role of Probiotics in Preventing Recurrent Urinary Tract Infections in Pregnant Women: A Randomized Control Trial #### Organization Study ID Info **ID:** 3388 #### Organization **Class:** OTHER **Full Name:** Frontier Medical and Dental College, Abbotabad ### Status Module #### Completion Date **Date:** 2024-01-15 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-23 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2023-11-14 **Type:** ACTUAL #### Start Date **Date:** 2023-06-23 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-05-15 **Study First Submit QC Date:** 2024-05-23 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Frontier Medical and Dental College, Abbotabad #### Responsible Party **Investigator Affiliation:** Frontier Medical and Dental College, Abbotabad **Investigator Full Name:** Dr Saif ur Rehman **Investigator Title:** Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Urinary tract infections (UTIs) are a significant public health problem affecting more than 150 million people worldwide and causing a significant economic impact of approximately US$ 6 billion annually. It is one of the most common infectious diseases after upper respiratory tract infections. More than 50% of women and at least 12% of men will be affected by urinary tract infections in their lifetime. The probiotic supplement was delivered as easy-to-swallow capsules specifically prepared to maintain the viability and stability of the Lactobacillus rhamnosus GG strain throughout the research period. Participants were told to take the probiotic supplement with water to maximise absorption and efficiency, ideally after meals. ### Conditions Module **Conditions:** - Urinary Tract Infections ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Randomised Controlled Trial ##### Masking Info **Masking:** SINGLE **Who Masked:** - PARTICIPANT **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 30 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The probiotic group received a daily oral supplement with Lactobacillus rhamnosus. The probiotic supplement was delivered as easy-to-swallow capsules. **Intervention Names:** - Dietary Supplement: Lactobacillus rhamnosus **Label:** Probiotic Group **Type:** EXPERIMENTAL #### Arm Group 2 **Intervention Names:** - Other: Control Group **Label:** Control Group **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - Probiotic Group **Description:** The probiotic supplement was delivered in the form of easy-to-swallow capsules. **Name:** Lactobacillus rhamnosus **Type:** DIETARY_SUPPLEMENT #### Intervention 2 **Arm Group Labels:** - Control Group **Description:** Participants in the control group were given a placebo that looked, tasted, and felt just like the probiotic pill. **Name:** Control Group **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** The test was performed to determine levels of neutrophils **Measure:** Urinary Detailed Report Values **Time Frame:** second trimester of pregnancy (about 14 week's gestation) and lasted until birth, a period of roughly 26 to 28 weeks. **Description:** Urine Culture: Urine samples were collected aseptically prior to and after intervention and cultured to detect bacterial pathogens linked with urinary tract infections. This assessment was carried out at two distinct time points: Pre-Intervention: Before beginning the probiotic intervention, baseline urine samples were taken to detect any existing bacterial illnesses and create a point of comparison. Post-Intervention: After the intervention period, individuals supplied an additional urine sample for culture investigation. This post-intervention evaluation sought to establish any changes in the prevalence of bacterial pathogens, particularly those known to cause urinary tract infection **Measure:** Urine Culture **Time Frame:** second trimester of pregnancy (about 14 week's gestation) and lasted until birth, a period of roughly 26 to 28 weeks. **Description:** leukocytes in urine were evaluated **Measure:** Leukocytes: **Time Frame:** second trimester of pregnancy (about 14 week's gestation) and lasted until birth, a period of roughly 26 to 28 weeks. **Description:** presence of nitrites in urine before and after intervention was investigated **Measure:** Nitrites: **Time Frame:** second trimester of pregnancy (about 14 week's gestation) and lasted until birth, a period of roughly 26 to 28 weeks. **Description:** Urinary pH values were measured **Measure:** pH **Time Frame:** second trimester of pregnancy (about 14 week's gestation) and lasted until birth, a period of roughly 26 to 28 weeks. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Pregnant women aged 18-40 year * History of recurrent urinary tract infections (two or more episodes in the past year). * Singleton pregnancy. Exclusion Criteria: * Multiple gestations. * History of preterm labor. * Chronic medical conditions (e.g., diabetes mellitus, immunodeficiency disorders). * Use of antibiotics or probiotics within the past month. **Gender Based:** True **Gender Description:** 14 week's gestation with diagnosed UTI **Maximum Age:** 40 Years **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Abbottābād **Country:** Pakistan **Facility:** Frontier Medical and Dental College **State:** KPK ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes - ID: D000014570 - Term: Urologic Diseases - ID: D000052776 - Term: Female Urogenital Diseases - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases - ID: D000052801 - Term: Male Urogenital Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC01 - Name: Infections - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions ### Condition Browse Module - Browse Leaves - ID: M14850 - Name: Recurrence - Relevance: LOW - As Found: Unknown - ID: M10283 - Name: Infections - Relevance: HIGH - As Found: Infection - ID: M6368 - Name: Communicable Diseases - Relevance: HIGH - As Found: Infection - ID: M17302 - Name: Urinary Tract Infections - Relevance: HIGH - As Found: Urinary Tract Infections - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown - ID: M17319 - Name: Urologic Diseases - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M14127 - Name: Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M27095 - Name: Male Urogenital Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007239 - Term: Infections - ID: D000003141 - Term: Communicable Diseases - ID: D000014552 - Term: Urinary Tract Infections ### Intervention Browse Module - Browse Branches - Abbrev: Ot - Name: Other Dietary Supplements - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: T355 - Name: Acidophilus - Relevance: HIGH - As Found: Next ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429345 **Brief Title:** Coenzyme Q10 Role in Prevention of Contrast Induced Nephropathy in Acute Coronary Syndrome Patients. **Official Title:** Possible Role of Coenzyme Q10 in Prevention of Contrast Induced Nephropathy in Patients With Acute Coronary Syndrome Undergoing Coronary Angiography With or Without Intervention. #### Organization Study ID Info **ID:** MS70/2024 #### Organization **Class:** OTHER **Full Name:** Ain Shams University ### Status Module #### Completion Date **Date:** 2024-11-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-06-04 **Type:** ACTUAL **Last Update Submit Date:** 2024-06-03 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2024-10-01 **Type:** ESTIMATED #### Start Date **Date:** 2024-06-01 **Type:** ESTIMATED **Status Verified Date:** 2024-03 #### Study First Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Study First Submit Date:** 2024-03-19 **Study First Submit QC Date:** 2024-05-23 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Ain Shams University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Is US Export:** True **Oversight Has DMC:** True ### Description Module **Brief Summary:** In this study the investigators aim to study the effect of supplementation of CoQ10 in decreasing the incidence of contrast induced acute kidney injury in patients with acute coronary syndrome undergoing coronary angiography. **Detailed Description:** Patients who fulfilled the inclusion criteria and agreed to participate in the study will be randomly divided into 2 groups using their computer generated random numbers that group a will receive the coenzyme Q10 in addition to the standard preventive measures and group b will receive only the standard preventive measures without the coenzyme Q10. ### Conditions Module **Conditions:** - Contrast-induced Nephropathy ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 250 **Type:** ESTIMATED **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Coenzyme Group received coenzyme Q10 in addition to the the standard preventive measures **Intervention Names:** - Drug: Coenzyme Q10 100 Milligrams Oral Capsule **Label:** Coenzyme Q10 100 Milligrams Oral Capsule **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Placebo Group received only the standard preventive measures **Intervention Names:** - Drug: Placebo **Label:** Placebo group **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Coenzyme Q10 100 Milligrams Oral Capsule **Description:** Patients will be randomly divided into two groups using a computer generated random number chart Coenzyme Q10 group will receive 400 milligrams coenzyme Q10 preoperative and 400 milligrams coenzyme Q10 for 3 days post operative in addition to the standard preventive measures. **Name:** Coenzyme Q10 100 Milligrams Oral Capsule **Other Names:** - Coenzyme Q10 **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo group **Description:** placebo group will receive only the standard preventive measures (as proper hydration pre and post operative)without the coenzyme Q10. **Name:** Placebo **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** a rise in serum creatinine of at least 0.5 mg/dL or a 25% increase from baseline within 48 to 72 hours after contrast exposure **Measure:** Percentage of the Creatinine rise in 1st 48-72 hours in ccu **Time Frame:** 48-72 hours ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients who are 18 years or older. * ST-elevation myocardial infarction (STEMI). * Non ST-elevation myocardial infarction( NSTEMI). * Unstable Angina (UA) Exclusion Criteria: * Renal transplant patients. * Preoperative bleeding . * Intraoperative bleeding or hypotension. * Patients taking any nephrotoxic medications **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Ramy Mohamed, Resident **Phone:** 01002820102 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Ramy Mohamed mostafa, Resident **Phone:** 01002820102 **Role:** CONTACT #### Locations **Location 1:** **City:** Cairo **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Ramy Mostafa, Resident - **Phone:** 01002820102 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Ramy Mohamed Mostafa, Resident - **Phone:** 01002820102 - **Role:** CONTACT **Country:** Egypt **Facility:** Ramy Mohamed Mostafa #### Overall Officials **Official 1:** **Affiliation:** Resident of cardiology department,Ain shams university **Name:** RAMY Mohamed **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000017202 - Term: Myocardial Ischemia - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000014652 - Term: Vascular Diseases - ID: D000014570 - Term: Urologic Diseases - ID: D000052776 - Term: Female Urogenital Diseases - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases - ID: D000052801 - Term: Male Urogenital Diseases ### Condition Browse Module - Browse Branches - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10698 - Name: Kidney Diseases - Relevance: HIGH - As Found: Nephropathy - ID: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M27545 - Name: Acute Coronary Syndrome - Relevance: HIGH - As Found: Acute Coronary Syndrome - ID: M10543 - Name: Ischemia - Relevance: LOW - As Found: Unknown - ID: M6546 - Name: Coronary Artery Disease - Relevance: LOW - As Found: Unknown - ID: M19506 - Name: Myocardial Ischemia - Relevance: LOW - As Found: Unknown - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: M17319 - Name: Urologic Diseases - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M14127 - Name: Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M27095 - Name: Male Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007674 - Term: Kidney Diseases - ID: D000054058 - Term: Acute Coronary Syndrome ### Intervention Browse Module - Ancestors - ID: D000018977 - Term: Micronutrients - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000014815 - Term: Vitamins ### Intervention Browse Module - Browse Branches - Abbrev: Micro - Name: Micronutrients - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Ot - Name: Other Dietary Supplements ### Intervention Browse Module - Browse Leaves - ID: M17201 - Name: Ubiquinone - Relevance: HIGH - As Found: Simulator - ID: M271049 - Name: Coenzyme Q10 - Relevance: HIGH - As Found: Mail - ID: M21009 - Name: Micronutrients - Relevance: LOW - As Found: Unknown - ID: M16885 - Name: Trace Elements - Relevance: LOW - As Found: Unknown - ID: M17558 - Name: Vitamins - Relevance: LOW - As Found: Unknown - ID: T383 - Name: Coenzyme Q10 - Relevance: HIGH - As Found: Mail ### Intervention Browse Module - Meshes - ID: D000014451 - Term: Ubiquinone - ID: C000024989 - Term: Coenzyme Q10 ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429332 **Acronym:** I-CATCHER **Brief Title:** International Care Bundle Evaluation in Cerebral Hemorrhage Research **Official Title:** International Care Bundle Evaluation in Cerebral Hemorrhage Research - a Batched Parallel Cluster-randomized Trial With a Baseline Period #### Organization Study ID Info **ID:** 2024-02523-01 #### Organization **Class:** OTHER **Full Name:** Region Skane ### Status Module #### Completion Date **Date:** 2027-03-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2026-10-01 **Type:** ESTIMATED #### Start Date **Date:** 2024-09-01 **Type:** ESTIMATED **Status Verified Date:** 2024-04 #### Study First Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Study First Submit Date:** 2024-05-14 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** The George Institute for Global Health, Australia #### Lead Sponsor **Class:** OTHER **Name:** Region Skane #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Spontaneous intracerebral haemorrhage (ICH) accounts for approximately 10-15% of all strokes but stands for 50% of stroke-related morbidity and mortality. Approximately half of all patients with ICH have a decreased level of consciousness at hospital admission. Despite this, intensive care and neurosurgical interventions are uncommon. A study conducted in low- and middle-income countries has demonstrated a beneficial effect of a treatment package consisting of early intensive blood pressure lowering, as well as the treatment of pyrexia and elevated blood glucose levels. The I-CATCHER team is now planning to conduct a similar study in Sweden and Australia, as well as in other high-income countries. The study has a clear focus on implementation, aiming to improve treatment and prognosis for patients with ICH within a few years. The purpose of I-CATCHER is to investigate whether a structured treatment package (Care Bundle) improves 3-month prognosis in patients with spontaneous ICH compared to standard care. **Detailed Description:** Spontaneous intracerebral hemorrhage (ICH) accounts for 10 to 15% of all strokes in high-income countries (HIC), and nearly twice this number in low-income to upper-middle-income countries (LMIC) (29.5%). It is the most devastating type of stroke given the high one-month case fatality of approximately 30-40%, and only 12-39% suffer persistent disability. Despite several advances in the management of acute ischemic stroke supported by numerous randomized controlled trials (RCT), progress in establishing novel interventions to improve outcomes for ICH has been slow. Still today, the diagnosis of ICH evokes pessimism among treating physicians, and patients may be withheld guideline adherent treatment for this reason. This nihilistic approach is presumably due to an over-estimation of poor outcome, often influenced by the neurologically devastating features commonly present at ICH admission. Additionally, the scarcity of RCTs providing strong evidence for treatment recommendations may contribute to a more reluctant approach in the acute setting of ICH, particularly when presenting with debilitating symptoms. The third INTEnsive care bundle with BP reduction in acute cerebral hemorrhage trial (INTERACT3) was recently published in 2023. This trial employed a stepped wedge cluster RCT design to evaluate the implementation of a Care Bundle protocol. This comprehensive protocol included early intensive BP lowering (EIBPL), management of pyrexia and hyperglycemia, and the early reversal of OAC treatment. The design of this trial drew inspiration from a post-hoc analysis of the INTERACT2 study that showed that the scoring of abnormal baseline variables, interventions included in the future INTERACT3 Care Bundle, independently predicted a poor functional outcome following ICH. The implementation of the time sensitive bundle of care in INTERACT3 resulted in an improved functional outcome at 6 months following ICH. However, as the trial included patients predominantly from LMIC, further studies are warranted to determine if these results are applicable to HIC with a more applicable Care Bundle for these populations. An earlier intervention study from the United Kingdom, published in 2019, studied a similar 'quality improvement' acute Care Bundle. This Care Bundle aimed to improve the speed of treatment delivery, access to acute care, and decrease case fatality following ICH. Despite certain limitations, including a non-randomized design, this study demonstrated significantly lower mortality rates in patients receiving the Care Bundle versus the pre-implementation standard of care. I-CATCHER is an international, multicenter, batched, parallel, cluster, randomized clinical trial (RCT) to assess a multifaceted package of protocols in a broad range of patients with acute ICH. In each batch, hospitals will be randomized into two groups according to the timing of the intervention (Care Bundle) over 3 phases (phase 1: usual care, phase 2: randomized evaluation - to intervention or usual care, phase 3: post-implementation follow-up - all hospitals implement the intervention). This design will capture consecutive patients with ICH and allow continued intervention in perpetuity as more hospitals join. Compared to a conventional stepped-wedge cluster RCT, the intervention effect in this design is less likely to be confounded by background temporal trends as only baseline and parallel comparison data (first 2 periods in bold black frame) are used to determine the effectiveness of the Care Bundle. All hospitals will be exposed to the Care Bundle which allows assessment of sustainability and integration of the intervention into routine practice. Each batch period is 18 months (6 months per phase); whole study will be rolled out in 2.5 years. This design involves implementation of an intervention package applied to all patients with ICH as part of routine care. Patients are only excluded if they refuse to have details of their management included and/or participate in follow-up procedures. Study site inclusion criteria: Organized systems of acute stroke care; no established comprehensive protocols for the management of ICH; suitable location, infrastructure and willingness to participate in clinical research; suitable numbers of ICH patients (at least 30 per year). Patient inclusion criteria: Adults (≥18 years) with spontaneous ICH confirmed by imaging and admitted hospital within 24 hours of the onset of symptoms. ### Conditions Module **Conditions:** - Intracerebral Hemorrhage - Intracerebral Haemorrhage - Intraventricular Hemorrhage - Stroke - Cerebrovascular Disease **Keywords:** - intracerebral hemorrhage - oral anticoagulant - blood pressure lowering - early intensive blood pressure lowering - care bundle - implementation study - reversal treatment - outcome - UW-mRS - Modified Rankin Scale ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** international multicentre, batched, cluster. Patients are not randomized, hospitals will be randomized. In each batch, hospitals are randomized into two groups according to the timing of the intervention (Care Bundle) over 3 phases (usual care, randomized evaluation, post-implementation follow-up): Phase 1 - baseline routine data collection, training and formative study (assess context and local resources, support adjustment of the protocol into local pathways) Phase 2 - start intervention implementation in the intervention group, data collection for comparison with usual care in the control group Phase 3 - all hospitals implement the intervention, data collection for quality improvement, assess sustainability and integration ##### Masking Info **Masking:** SINGLE **Masking Description:** Treatment allocation is on a site-level and not on an individual level. The allocation is not blinded. Follow-up clinical outcome assessors, who have no prior association with the study and are unaware of the patients' allocation to either the intervention or control arm, will contact the participant by telephone at 6 months. At the initiation of contact, study subjects will be urged not to disclose their treatment allocation. **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 3500 **Type:** ESTIMATED **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** A range of implementation methods will be used to introduce an active Care Bundle with time- and target-based metrics that involve the rapid correction of abnormal physiological variables over days or hospital discharge (or death, if sooner) and referral pathways **Intervention Names:** - Other: Reversal of Oral anticoagulation within 30 minutes - Other: Early intensive blood pressure lowering - Other: Treatment of pyrexia - Other: Hyperglycemia treatment - Other: Do-not-resuscitate (DNR) or withdrawal of care - Other: Referral to Intensive Care - Other: Referral to Neurosurgery - Diagnostic Test: Repeat brain imaging **Label:** Intervention group **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** For patients in the usual-care group, decisions about the location of care delivery, investigations, monitoring, and all treatments are made by the treating clinical team. Data will be collected regarding the management of patients, including insertion of invasive monitoring devices, intravenous fluid resuscitation, BP lowering, vasoactive support, glycemic control, mechanical ventilation, neurosurgery, and other supportive therapy. **Intervention Names:** - Other: Standard care **Label:** Usual care **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Intervention group **Description:** In situations of either an elevated INR with the use of warfarin - treatment with either 3- or 4-factor prothrombin complex concentrate (PCC) or fresh frozen plasma (FFP) within 30 minutes of hospital arrival to reach and maintain an INR target \<1.3; or where there has been recent use (\<48 hours) of a direct oral anticoagulant (DOAC), use of an appropriate reversal agent within 30 minutes, where available, and according to local approvals. **Name:** Reversal of Oral anticoagulation within 30 minutes **Other Names:** - OAC reversal **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - Intervention group **Description:** A systolic blood pressure (BP) target of 130-140 mmHg within 30 minutes of commencing treatment is strived for, and to maintain this BP level for the first 7 days (for patients presenting with blood pressure \<200 mmHg). If blood pressure ≥200 and \<220, a target BP of 160 mmHg should be targeted at 30 minutes, and 130-140 mmHg should be achieved in 60 minutes. If BP ≥220, target BP of 160 mmHg and should be achieved in 60 minutes. **Name:** Early intensive blood pressure lowering **Type:** OTHER #### Intervention 3 **Arm Group Labels:** - Intervention group **Description:** To achieve a body temperature target \<37.5 °C **Name:** Treatment of pyrexia **Type:** OTHER #### Intervention 4 **Arm Group Labels:** - Intervention group **Description:** To maintain a blood glucose level 7-10 mmol/L **Name:** Hyperglycemia treatment **Type:** OTHER #### Intervention 5 **Arm Group Labels:** - Intervention group **Description:** Refrain from the use of DNR or withdrawal of care orders for 48 hours **Name:** Do-not-resuscitate (DNR) or withdrawal of care **Type:** OTHER #### Intervention 6 **Arm Group Labels:** - Intervention group **Description:** Immediate (\<30 min) referral to intensive care if airway, breathing and/or circulation are compromized **Name:** Referral to Intensive Care **Type:** OTHER #### Intervention 7 **Arm Group Labels:** - Intervention group **Description:** Immediate (\<30 min) referral to neurosurgery if any of the following criteria are fulfilled: * Large and/or rapidly evolving supratentorial ICH (\>20 ml volume) * Any intraventricular extension * Posterior fossa bleed, irrespective of volume * Suspicion of a vascular malformation, independent of volume or location * Reduction in reaction to sensory stimulation or drowsiness **Name:** Referral to Neurosurgery **Type:** OTHER #### Intervention 8 **Arm Group Labels:** - Intervention group **Description:** Repeat 6-12-hour brain imaging with the physicians choice of modality, preferably computed tomography (CT), if clinical deterioration or the patient received OAC reversal treatment **Name:** Repeat brain imaging **Type:** DIAGNOSTIC_TEST #### Intervention 9 **Arm Group Labels:** - Usual care **Description:** For patients in the usual-care group, decisions about the location of care delivery, investigations, monitoring, and all treatments are made by the treating clinical team. Data will be collected regarding the management of patients, including insertion of invasive monitoring devices, intravenous fluid resuscitation, BP lowering, vasoactive support, glycemic control, mechanical ventilation, neurosurgery, and other supportive therapy. **Name:** Standard care **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** The modified Rankin Scale (mRS) is an efficient, reliable, and simple functional outcome measure widely used as a primary endpoint in clinical trials for acute stroke. However, being an ordered categorical scale, it may not reflect potentially unequal differences in perceived quality of life associated with certain 1-point shifts vs others. Utility-weighted mRS is a score that weighs the mRS against a health utility scale, which defined as the desirability of a specific health outcome, facilitates comparisons of health-related quality of life across an array of clinical settings. Utility weights, as referred to hereafter, reflect the spectrum between perfect health (a score of 1) and outcomes worse than death (where death is a score of 0 and negative values indicate an outcome worse than death). The primary outcome is UW-mRS at 3 months and will be analyzed by means of a linear regression, with mRS as a dependent variable with 7 levels (0 \[no residual symptom\] to 6 \[death\]). **Measure:** Evaluation of functional outcome based on the Utility Weighted modified Rankin Scale score **Time Frame:** 180±30 days #### Secondary Outcomes **Description:** The assessment of shifts in the distribution of mRS scores through the evaluation of scores in ordinal groups **Measure:** Ordinal shift analysis of mRS **Time Frame:** 180 days±30 days **Description:** This will be assessed using the EuroQoL Group 5-Dimension self-report questionnaire (EQ-5D). The VAS is a scale from 0 (worst imaginable health state) to 100 (best imaginable health state). **Measure:** Assessment of health-related quality of life (HRQoL) **Time Frame:** 180 days±30 days **Description:** Binary secondary outcomes will be analyzed by means of standard GEE or random-effects regression with a logistic link and/or time-to-event type endpoints using the Cox model with a sandwich formula or a frailty model. **Measure:** Poor outcome defined as mRS 3-6 **Time Frame:** 180 days±30 days **Description:** Binary secondary outcomes will be analyzed by means of standard GEE or random-effects regression with a logistic link and/or time-to-event type endpoints using the Cox model with a sandwich formula or a frailty model. **Measure:** Separate outcomes for death and disability **Time Frame:** 180 days±30 days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Adults (age ≥18 years) * Non-contrast computerized tomography (NCCT) imaging-verified diagnosis of spontaneous intracerebral haemorrhage * ≤24 hours from symptom onset or presumed symptom onset (last seen well) Exclusion Criteria: * Previous care limitation * End-stage comorbidity with short life-expectancy (\<6 m; e.g. terminal cancer) * ICH caused by brain tumor or cerebral venous thrombosis * Clinical signs of brain herniation at first presentation (unresponsive patient with bilaterally fixed, maximally dilated pupils) * Pregnant women beyond 22 weeks gestation may only be included after thorough discussion with an obstetrician to determine risks vs benefit. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Teresa Ullberg, MD, PhD **Phone:** 0046175057 **Role:** CONTACT #### Locations **Location 1:** **City:** Sydney **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Menglu Ouyang, PhD, MPH - **Phone:** 0061280524808 - **Role:** CONTACT ***Contact 2:*** - **Name:** Menglu Ouyang, PhD, MPH - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Australia **Facility:** The George Institute for Global Health **Zip:** NSW 2000 **Location 2:** **City:** Malmö **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Teresa Ullberg, MD, PhD - **Phone:** +4646175057 - **Role:** CONTACT ***Contact 2:*** - **Name:** Trine Apostolaki-Hansson, MD PhD - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 3:*** - **Name:** Fredrik Buchwald, MD PhD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Sweden **Facility:** Region Skåne, Skåne University Hospital in Malmö, Department of Neurology **Zip:** 20502 ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** GBD 2019 Stroke Collaborators. Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol. 2021 Oct;20(10):795-820. doi: 10.1016/S1474-4422(21)00252-0. Epub 2021 Sep 3. **PMID:** 34487721 **Citation:** Qureshi AI, Tuhrim S, Broderick JP, Batjer HH, Hondo H, Hanley DF. Spontaneous intracerebral hemorrhage. N Engl J Med. 2001 May 10;344(19):1450-60. doi: 10.1056/NEJM200105103441907. No abstract available. **PMID:** 11346811 **Citation:** van Asch CJ, Luitse MJ, Rinkel GJ, van der Tweel I, Algra A, Klijn CJ. Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis. Lancet Neurol. 2010 Feb;9(2):167-76. doi: 10.1016/S1474-4422(09)70340-0. Epub 2010 Jan 5. **PMID:** 20056489 **Citation:** Parry-Jones AR, Sammut-Powell C, Paroutoglou K, Birleson E, Rowland J, Lee S, Cecchini L, Massyn M, Emsley R, Bray B, Patel H. An Intracerebral Hemorrhage Care Bundle Is Associated with Lower Case Fatality. Ann Neurol. 2019 Oct;86(4):495-503. doi: 10.1002/ana.25546. Epub 2019 Aug 16. **PMID:** 31291031 **Citation:** Hemphill JC 3rd, Newman J, Zhao S, Johnston SC. Hospital usage of early do-not-resuscitate orders and outcome after intracerebral hemorrhage. Stroke. 2004 May;35(5):1130-4. doi: 10.1161/01.STR.0000125858.71051.ca. Epub 2004 Mar 25. **PMID:** 15044768 **Citation:** Becker KJ, Baxter AB, Cohen WA, Bybee HM, Tirschwell DL, Newell DW, Winn HR, Longstreth WT Jr. Withdrawal of support in intracerebral hemorrhage may lead to self-fulfilling prophecies. Neurology. 2001 Mar 27;56(6):766-72. doi: 10.1212/wnl.56.6.766. **PMID:** 11274312 **Citation:** Zahuranec DB, Brown DL, Lisabeth LD, Gonzales NR, Longwell PJ, Smith MA, Garcia NM, Morgenstern LB. Early care limitations independently predict mortality after intracerebral hemorrhage. Neurology. 2007 May 15;68(20):1651-7. doi: 10.1212/01.wnl.0000261906.93238.72. **PMID:** 17502545 **Citation:** Song L, Hu X, Ma L, Chen X, Ouyang M, Billot L, Li Q, Munoz-Venturelli P, Abanto C, Pontes-Neto OM, Antonio A, Wasay M, Silva A, Thang NH, Pandian JD, Wahab KW, You C, Anderson CS; INTERACT3 investigators. INTEnsive care bundle with blood pressure reduction in acute cerebral hemorrhage trial (INTERACT3): study protocol for a pragmatic stepped-wedge cluster-randomized controlled trial. Trials. 2021 Dec 20;22(1):943. doi: 10.1186/s13063-021-05881-7. **PMID:** 34930428 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000020300 - Term: Intracranial Hemorrhages - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M22306 - Name: Stroke - Relevance: LOW - As Found: Unknown - ID: M9556 - Name: Hemorrhage - Relevance: HIGH - As Found: Hemorrhage - ID: M5792 - Name: Cerebral Hemorrhage - Relevance: HIGH - As Found: Intracerebral Hemorrhage - ID: M5810 - Name: Cerebrovascular Disorders - Relevance: HIGH - As Found: Cerebrovascular Disease - ID: M11910 - Name: Mitral Valve Insufficiency - Relevance: LOW - As Found: Unknown - ID: M22113 - Name: Intracranial Hemorrhages - Relevance: LOW - As Found: Unknown - ID: M5204 - Name: Brain Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002543 - Term: Cerebral Hemorrhage - ID: D000002561 - Term: Cerebrovascular Disorders - ID: D000006470 - Term: Hemorrhage ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: AnCoag - Name: Anticoagulants - Abbrev: Coag - Name: Coagulants - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: Ot - Name: Other Dietary Supplements ### Intervention Browse Module - Browse Leaves - ID: M11767 - Name: Metronidazole - Relevance: LOW - As Found: Unknown - ID: M17602 - Name: Warfarin - Relevance: LOW - As Found: Unknown - ID: M4244 - Name: Anticoagulants - Relevance: LOW - As Found: Unknown - ID: M16676 - Name: Thrombin - Relevance: LOW - As Found: Unknown - ID: M4854 - Name: Benzocaine - Relevance: LOW - As Found: Unknown - ID: T433 - Name: Tannic Acid - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429319 **Brief Title:** Intra-articular Polyacrylamide Hydrogel in Gonarthrosis **Official Title:** Multicenter Open Post-registration Study of the Safety and Effectiveness of the Medical Device HBIS Endoprosthesis of Synovial Fluid NOLTREX™ According to TU 9398-00152820385-2015 for Intraarticular Administration in the Treatment of Gonarthrosis. #### Organization Study ID Info **ID:** IA/PAAG-SI/OA/2020 #### Organization **Class:** INDUSTRY **Full Name:** Research Centre BIOFORM ### Status Module #### Completion Date **Date:** 2024-02-20 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2021-05-12 **Type:** ACTUAL #### Start Date **Date:** 2020-05-28 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Study First Submit Date:** 2020-08-14 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Research Centre BIOFORM #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** The aim of this open post-marketing study is to assess safety and efficacy duration of HBIS IA injection after 1st and 2nd course in patients with gonarthrosis with long-term follow-up **Detailed Description:** Hydrous biopolymer with silver ions (further - HBIS) under trademark NOLTREX™ based on polyacrylamide hydrogel is intended for a symptomatic effect leading to the decrease of joint pain intensity and improvement of functional joint characteristics. Therefore, HBIS is intended for symptom-modifying therapy of joint osteoarthritis (hereinafter - OA). The aim of this study is to estimate safety and efficacy of intra-articular injections of HBIS after 1st and 2nd course in patients with gonarthrosis with long-term follow-up. Patients, who received 1 сourse - 2 injections of NOLTREX™ in first 6-month study IA/PAAG-SI/OA/2019, will receive a repeated course of treatment strictly according to indications. The scheme of the 2nd Course is one or two 4.0 ml dosage injections of NOLTREX™ with 1-week interval on week 0 or week 13 of the study. Outcomes will estimate by WOMAC Index at Week 13 and at Week 25. ### Conditions Module **Conditions:** - Osteoarthritis **Keywords:** - intra-articular - polyacrylamide hydrogel - PAAG - HBIS (Hydrous biopolymer with silver ions) - NOLTREX ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP **Intervention Model Description:** This is open-label MD NOLTREX™ safety assessment study includes eligible and non-eligible patients who received study MD as part of the IA/PAAG-SI/OA/2019 study. It was planned that 72 patients would take part in the study. In fact, 67 patients were screened into the study because not all patients from CS1 progressed to CS2; 2 of these patients failed screening measures, so the final population included 65 patients. ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 67 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Sixty-seven patients were screened for the study; 2 of them were screening failures, therefore, 65 patients were randomized to participate in the study, who were conventionally divided into subgroups: * Group A included 5 patients. Patients in group A received 2 courses of therapy: both within IA/PAAG-SI/OA/2019 study and at Visit 1 (and as indicated at Visit 2) of the IA/PAAG-SI/OA/2020 study. * Group B - 43 patients. Patients in group B also received 2 courses of therapy: both within IA/PAAG-SI/OA/2019 study and at Visit 3 (and as indicated at Visit 4) of the IA/PAAG-SI/OA/2020 study. * Group C - 17 patients. Group C included patients who received only one course of injections in the placebo-controlled study IA/PAAG-SI/OA/2019. There were no early withdrawals from the study. **Intervention Names:** - Device: hydrous biopolymer with silver ions "Argiform" **Label:** hydrous biopolymer with silver ions "Argiform" **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - hydrous biopolymer with silver ions "Argiform" **Description:** Patients will receive an injection of MD NOLTREX™ into the target knee joint. MD will be administered in accordance with the instructions for use of MD NOLTREX™: 4.0 ml per injection (2.5 + 1.5 ml, or 2.0 + 2.0 ml from two syringes through one needle \[one puncture\]) at intervals of one week. The course within this open study is a maximum of 2 injections. The number of injections is determined by the doctor depending on the stage of gonarthrosis and the clinical response **Name:** hydrous biopolymer with silver ions "Argiform" **Other Names:** - Polyacrylamide hydrogel with silver ions - Synovial fluid endoprosthesis NOLTREX™ **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** By Visit 3, the mean WOMAC-T (Osteoarthritis Index Total Score) compared to Visit 1 of the IA/PAAG-SI/OA/2019 study has changed by 430.20 ± 470.50 (95% CI -1014.40 - 154.00) in patients from group A, by 727.16 ± 353.78 (95% CI -836.04 - -618.28) in patients from group B, by 654.35 ± 241.28 (95% CI -778.41 - -530 ,30) in patients from group C. Intergroup differences were not statistically significant (p = 0.169). By Visit 5, the mean WOMAC-T score compared to Visit 1 of the IA/PAAG-SI/OA/2019 study has changed by 470.60 ± 495.56 (95% CI -1085.92 - 144.72) in patients from group A, by 829.53 ± 367.38 (95% CI -942.60 - -716.47) in patients from group B, by 688.53 ± 231.50 (95% CI -807.56 - -569 .50) in patients from group C. Intergroup differences were not statistically significant (p = 0.057). **Measure:** Change of the total score of WOMAC scale (WOMAC-T) **Time Frame:** Change in WOMAC Total Score (WOMAC-T) at Visit 3 (Week 11), Visit 5 (Week 23) from baseline at Visit 0 (Screening) of the open-label study and from baseline at Visit 1 (Week 1) of IA/PAAG-SI/OA/2019 study; #### Secondary Outcomes **Description:** By Visit 3, the mean WOMAC-A (pain subscale) score compared to Visit 1 of the IA/PAAG-SI/OA/2019 study has decreased by 87.80 ± 87.45 (95% CI -196.38 - 20.78) in patients from group A, by 146.00 ± 74.46 (95% CI -168.91 - -123.09) in patients from group B, by 151.88 ± 64.56 (95% CI -185.07 - -118 .69) in patients from group C. Intergroup differences were not statistically significant (p = 0.212). By Visit 5, the mean WOMAC-A score compared to Visit 1 of the IA/PAAG-SI/OA/2019 study has decreased by 95.80 ± 95.49 (95% CI -214.37 - 22.77) in patients from group A, by 163.05 ± 75.82 (95% CI -186.38 - -139.71) in patients from group B, by 155.06 ± 63.49 (95% CI -187.70 - -122 .41) in patients from group C. Intergroup differences were not statistically significant (p = 0.168). **Measure:** Change of the pain subscale score (WOMAC-A) **Time Frame:** Change in the subscale of pain (WOMAC-A) at Visit 3 (Week 11), Visit 5 (Week 23) from baseline at Visit 0 (Screening) of the open-label study and from baseline at Visit 1 (Week 1) of IA/PAAG-SI/OA/2019 study; **Description:** By Visit 3, the mean WOMAC-B (subscale for assessing stiffness) score compared to Visit 1 of the IA/PAAG-SI/OA/2019 study has decreased by 62.80 ± 69.82 (95% CI -149.49 - 23.89) in patients from group A, by 67.19 ± 40.91 (95% CI -79.78 - -54.60) in patients from group B, by 48.71 ± 28.08 (95% CI -63.14 - -34 .27) in patients from group C. Intergroup differences were not statistically significant (p = 0.291). By Visit 5, the mean WOMAC-B score compared to Visit 1 of the IA/PAAG-SI/OA/2019 study has decreased by 66.40 ± 70.26 (95% CI -153.64 - 20.84) in patients from group A, by 74.60 ± 42.67 (95% CI -87.74 - -61.47) in patients from group B, by 57.82 ± 28.11 (95% CI -72.27 - -43 .37) in patients from group C. Intergroup differences were not statistically significant (p = 0.376). **Measure:** Change of rigidity (WOMAC-B) and functionality (WOMAC-C) subscale scores **Time Frame:** Change in the subscale of stiffness (WOMAC-B) and functionality (WOMAC-C) at Visit 3 (Week 11), Visit 5 (Week 23) from baseline at Visit 0 (Screening) of the open-label study and from baseline at Visit 1 (Week 1) of IA/PAAG-SI/OA/2019 study; **Description:** During the period of this study (CS2), the decrease of this indicator continued, and at Visit 3, VAS scores of groups A, B and C patients were 11.2 ± 6.53, 29.07 ± 15.29 and 21.53 ± 6.32 mm, respectively, and by Visit 5 the indicators decreased to 6.2 ± 5.59, 16.56 ± 12.32 and 4.88 ± 3.14 mm, respectively. At both visits, the between-group differences were statistically significant, which was due to the higher scores in group B. Combined score of groups A and B was compared with the score in group C, and there were also statistically significant between-group differences (p \< 0.05 from Visit 3 to Visit 5), which was consistent with the approach to dividing patients into groups: patients in group C received only one course of injections in the placebo-controlled study CS1 (IA/PAAG-SI/OA/2019) and had no indications for repeated injections, while patients in groups A and B have a requirement to receive two courses of therapy **Measure:** Intensity of pain in the target knee joint (100-mm VAS) **Time Frame:** Change in the severity of pain in the target knee joint according to 100 mm visual analogue scale (100 mm VAS) at Visit 2 (week 1), Visit 3 (week 11), Visit 5 (week 23) from baseline at Visit 0 (Screening) of the open-label safety study and from baseli **Description:** At visit 3 patients evaluation scores from Group B as, significant improvement was indicated by 3 patients, improvement - by 23 patients, weak improvement - 15 patients and no changes -0 patients. from patients Group C improvement was indicated by - 4 patients, weak improvement - 8 patients and no changes - 5 patients and from Group A patients was not indicate any changes with p (between the groups \<0.001) At visit 5 patients Group B scores as, significant improvement was indicated by 6 patients, improvement - by 25 patients, weak improvement - 12 patients and no changes -0 patients. from patients Group C improvement was indicated by - 16 patients, weak improvement - 1 patient and no changes - 0 patients and from Group A patients - significant improvement was indicated by - 4 patients and improvement were indicated by 1 patient, no changes were indicated by 0 patients with p (between the groups \<0.001) **Measure:** Patient's assessment of the treatment efficacy **Time Frame:** Evaluation of treatment effectiveness by the patient (using a scale from 1 - a definitive deterioration to 6 - a significant improvement) at Visits 3 and 5 (OEP-w11 and OEP-w23 scores, respectively); **Description:** At visit 3 investigators evaluation for Group B scores as significant improvement was indicated by 3 investigators - improvement - by 23, weak improvement - 14 and no changes -3 investigators. from Group C - improvement was indicated by - 4 investigators, weak improvement - 8 and no changes - 5 and from Group A- significant improvement was indicated by - 2 investigators improvement - by 2 and weak improvement by 2 investigators with p (between the groups \<0.001) At visit 5 investigators evaluation for Group B scores as significant improvement was indicated by 3 investigators, improvement - by 23, weak improvement - 14 and no changes -3 from Group C - improvement was indicated by - 4, weak improvement - 8 and no changes - 5 and from Group A significant improvement was indicated by - 2 investigators improvement were indicated by 2 and weak improvement by 2 investigators with p (between the groups \<0.001) **Measure:** Investigator's assessment of the treatment efficacy **Time Frame:** Evaluation of treatment effectiveness by the investigator (using a scale from 1 - a definitive deterioration to 6 - a significant improvement) at Visits 3 and 5 (OEI-w11 and OEI-w23 scores, respectively); **Description:** The results obtained show a favorable long-term effect of intra-articular NOLTREX™ in the treatment of Kellgren-Lawrence radiological stage II-III knee osteoarthritis on the function of the knee joint. It was impossible to evaluate the need for NSAID due to the fact during the study period of CS 2, no such cases were recorded. **Measure:** Total number of NSAID tablets taken **Time Frame:** Assessment of the total number of NSAID tablets taken according to the patient's diary starting from Day 1, at Visits 3 and 5 (NSAID-w11 and NSAID-w23, respectively); **Description:** The JSN score of the target knee at Visit 5 of the open-label study compared with the baseline at Visit 0 of the IA/PAAG-SI/OA/2019 study in patients from group A was -0.02 ± 0.05, in patients from group B - 0.00 ± 0.19, in patients from group C - 0.02 ± 0.08. Intergroup differences were not statistically significant (p = 0.379). The JSN index of the target knee joint reflects the disease progression, and the absence of changes or a decrease in the index indicates a protective effect of NOLTREX™. **Measure:** The JSN score of the target knee **Time Frame:** The JSN score of the target knee at Visit 5 of the open-label study compared with the baseline at Visit 0 of the IA/PAAG-SI/OA/2019 study retrospectively. **Description:** The results obtained show a favorable long-term effect of intra-articular NOLTREX™ in the treatment of Kellgren-Lawrence radiological stage II-III knee osteoarthritis on the function of the knee joint. It was impossible to evaluate the need for paracetamol due to the fact during the study period of CS 2, no such cases were recorded. **Measure:** Total number of paracetamol tablets taken **Time Frame:** Assessment of the total number of paracetamol tablets taken according to the patient's diary (one tablet = 500 mg) starting from Day 1, at Visits 3 and 5 (PARACETAMOL-w11 and PARACETAMOL-w23 scores, respectively); ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Men and women above 50 years; * A signed Patient Informed Consent Form by the study participant; * Verified knee osteoarthritis in accordance with the ACR (knee pain combined with one of the following signs: age above 50 years, knee crepitus or morning joint stiffness lasting for less than 30 minutes combined with radiologic signs of knee osteoarthritis); * Kellgren Lawrence radiological grade II-III knee osteoarthritis with the predominant involvement of the medial tibiofemoral region of the knee joint; * Completion of participation in clinical study protocol IA / PAAG-SI / OA / 2019 in the NOLTREX ™ medical device group with the completion of all 5 visits (25 weeks) Exclusion Criteria: 1. Pregnancy and breastfeeding; 2. History of trauma or surgery on the target knee joint; 3. Instability of the target knee joint; 4. Microcrystalline arthropathies (according to the history and taking into account clinical manifestations); 5. History of systemic inflammatory diseases (rheumatoid arthritis, systemic lupus erythematosus, etc.); 6. Seronegative spondyloarthritis and reactive arthritis; 7. Increased rheumatoid factor; 8. Increased uric acid \> 360 µmol/l; 9. Intra-articular injection into the target knee joint: * hyaluronates - within 12 months prior to patient enrollment in the study; * other synovial fluid endoprostheses (except for NOLTREX™ in the IA/PAAG- SI/OA/2019 study) within 24 months; * glucocorticoids - within 1 month before enrollment in the study; * NSAIDs - intra-articular injection at any time in the history. 10. Systemic pain medications (NSAIDs, opioid analgesics) within 1 week prior to Visit 0; 11. Effusion in the target joint; 12. The presence of inflammation or infection in the target joint, synovitis; 13. The need for continuous use of glucocorticoids in any dosage form; 14. Use of paracetamol within 48 hours prior to Visit 0; 15. A positive blood test result for one or more of the following infections: HIV, hepatitis B and C, syphilis; 16. Severe liver disease, defined as an increase in one of the following: ALT, AST, alkaline phosphatase, total bilirubin, GGT more than 3 times the upper limit of normal; 17. Kidney disease with a glomerular filtration rate as assessed by the Cockcraft-Gault formula less than 60 mL/min/1.73 m2 (stages III-V chronic kidney disease \[CKD\]); 18. Clinical manifest coxarthrosis; 19. Severe decompensated chronic or acute diseases and other conditions or other causes that, in the investigator's opinion, may prevent the patient from participating in the study or affect the study results ; 20. Participation in any other clinical study other than study IA/PAAG-SI/OA/2019 within 90 days prior to enrollment in the study. **Minimum Age:** 50 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Moscow **Country:** Russian Federation **Facility:** Non-budgetary healthcare facility "Railway clinical hospital n.a. Semashko N.A. at Lublino, OJSC "Russian Railways" **Location 2:** **City:** Omsk **Country:** Russian Federation **Facility:** "Clinical Diagnostic Center "Ultramed", LLC **Location 3:** **City:** Saint Petersburg **Country:** Russian Federation **Facility:** Private Healthcare Facilty "Clinical hospital "RZHD-Medicina" of the city Saint-Petersburg **Location 4:** **City:** Yaroslavl **Country:** Russian Federation **Facility:** State budgetary healthcare facility of Yaroslavl Region "Clinical hospital №3" ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001168 - Term: Arthritis - ID: D000007592 - Term: Joint Diseases - ID: D000009140 - Term: Musculoskeletal Diseases - ID: D000012216 - Term: Rheumatic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases ### Condition Browse Module - Browse Leaves - ID: M22168 - Name: Osteoarthritis, Knee - Relevance: HIGH - As Found: Gonarthrosis - ID: M12926 - Name: Osteoarthritis - Relevance: HIGH - As Found: Osteoarthritis - ID: M4476 - Name: Arthritis - Relevance: LOW - As Found: Unknown - ID: M10621 - Name: Joint Diseases - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: M15045 - Name: Rheumatic Diseases - Relevance: LOW - As Found: Unknown - ID: M6323 - Name: Collagen Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000010003 - Term: Osteoarthritis - ID: D000020370 - Term: Osteoarthritis, Knee ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429306 **Brief Title:** Study of Dexycu in Treating Intraocular Inflammation **Official Title:** A Phase 3,Prospective, Randomized, Double-masked, Placebo-controlled, Parallel Study to Evaluate the Efficacy, PK and Safety of 9% Dexamethasone Intraocular Injection for the Treatment of Inflammation Associatedwith Cataract Surgery #### Organization Study ID Info **ID:** OT-502-001 #### Organization **Class:** INDUSTRY **Full Name:** Ocumension Therapeutics (Shanghai) Co., Ltd ### Status Module #### Completion Date **Date:** 2024-04-09 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2023-11-24 **Type:** ACTUAL #### Start Date **Date:** 2022-08-22 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Study First Submit Date:** 2024-05-11 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Ocumension Therapeutics (Shanghai) Co., Ltd #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** This is a phase III, prospective, randomised, double-masked, placebo-controlled, parallel-design, multicenter study of the efficacy, safety and pharmacokinetics of 9% dexamethasone intraocular injection for the treatment of inflammation associated with cataract surgery. **Detailed Description:** This is a prospective, randomized, double-blindmasked, placebo-controlled, parallel- design, multicenter study of subjects over 40 years undergoing cataract surgery. Subjects meet the inclusion criteria and do not meet any exclusion criteria are randomiszed to the dexamethasone implant group or placebo group at a ratio of 2:1. Subjects received a single does injection in the study eye immediately after the completion of cataract surgery. The investigational drug comes with a special injection device and injection guide. All subjects will be administered to the study eye with quinolone topical antibiotic eye drops or their equivalent 3 days before and 7 days after surgery. ### Conditions Module **Conditions:** - Inflammation - Cataract **Keywords:** - Cataract Surgery - Postoperative Inflammation ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 285 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Dexamethasone implant single injection in the treatment eye after cataract surgery. **Intervention Names:** - Drug: Dexycu **Label:** Dexamethasone intraocular injection **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Blank placebo single injection in the treatment eye after cataract surgery. **Intervention Names:** - Drug: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Dexamethasone intraocular injection **Description:** 5ul dexamethasone, concentration: 103.4 μg/μl, equivalent to 517μg dexamethasone **Name:** Dexycu **Other Names:** - Investigational product **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** Acetyl triethyl citrate **Name:** Placebo **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The primary efficacy outcome is anterior chamber cell clearing in the study eye at Day 8. The slit lamp examination for anterior chamber cells (ACC) is a recognized way to measure inflammation in the anterior chamber. During the slit lamp examination, the number of anterior chamber cells are quantified and graded: grade 0 (absent, 0 cells), grade 1 (1 to 5 cells), grade 2 (6 to 15 cells), grade 3 (16 to 30+ cells), or grade 4 (hypopyon). Anterior chamber cell clearing occurs when all the ACC are absent (grade 0). **Measure:** Anterior chamber cell clearing rate **Time Frame:** DAY 8 #### Secondary Outcomes **Description:** The secondary efficacy outcome is anterior chamber cell clearing in the study eye at Day 1 \& 3 \& 15 \& 30. The slit lamp examination for anterior chamber cells (ACC) is a recognized way to measure inflammation in the anterior chamber. During the slit lamp examination, the number of anterior chamber cells are quantified and graded: grade 0 (absent, 0 cells), grade 1 (1 to 5 cells), grade 2 (6 to 15 cells), grade 3 (16 to 30+ cells), or grade 4 (hypopyon). Anterior chamber cell clearing occurs when all the ACC are absent (grade 0). **Measure:** Anterior chamber cell clearing rates **Time Frame:** DAY 1 & 3 & 15 & 30 **Description:** Percentage of subjects with anterior chamber flare grade 0 at Day 1, 3, 8, 15, and 30. The slit lamp examination for anterior chamber flare (ACF) is a recognized way to measure inflammation in the anterior chamber. During the slit lamp examination, the number of anterior chamber cells are quantified and graded: grade 0 (absent), grade 1 (trace), grade 2 (mild intensity), grade 3 (moderate intensity), or grade 4 (strong intensity). Anterior chamber flare clearing occurs when all the ACC are absent (grade 0). **Measure:** Anterior chamber flare clearing rates **Time Frame:** DAY 1 & 3 & 8 & 15 & 30 **Description:** The secondary efficacy outcome is anterior chamber cell \& flare clearing in the study eye at Day 1 \& 3 \& 15 \& 30. The slit lamp examination for anterior chamber cells \& flare (ACCF) is a recognized way to measure inflammation in the anterior chamber. **Measure:** Anterior chamber cell & flare clearing rates **Time Frame:** DAY 1 & 3 & 15 & 30 **Description:** Calculate the mean score of anterior chamber cell and flare separately at Day 8 and 15. **Measure:** Mean anterior chamber cell score and mean anterior chamber flare score **Time Frame:** DAY 8 & 15 **Description:** Calculate the mean socre of anterior chamber cell + flare at Day 8 and 15. **Measure:** Mean anterior chamber cell + flare score **Time Frame:** DAY 8 &15 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. The patient must provide written informed consent by signing the Informed Consent approved by the Institutional Review Board (IRB). 2. Male or female patients at least 40 years of age scheduled for unilateral cataract surgery by phacoemulsification with posterior chamber intraocular lens implantation. 3. The patient must demonstrate best corrected visual acuity (BCVA) of 20/30-20/200 in the study eye and better than 20/200 in the fellow eye. 4. The patient must be considered by the Investigator to have visual acuity potential. greater than 20/30 in the study eye. 5. The patient must have a corneal endothelial cell count by specular microscopy in the study eye of at least 2000 cells/mm2 with normal cell morphology. 6. A female patient of childbearing potential must have a negative pregnancy test on Day 0 and be using an effective method of birth control from Screening for the duration of the study. 7. The patient must be willing and able to understand and comply with the study procedures and to communicate meaningfully with study personnel. Exclusion Criteria: 1. Patients who have used any ocular, topical or oral corticosteroids within 7 days prior to Day 0. 2. Patients who have received a periocular corticosteroid injection in the study eye in the 3 months prior to screening. 3. Patients who have received any intravitreal corticosteroid delivery vehicle (e.g.,Retisert, Ozurdex, Iluvien) in the study eye at any time. 4. Patients who anticipate requiring treatment with any corticosteroids( by any route,except inhalation), during the study. 5. Patients with an allergy or hypersensitivity to dexamethasone. 6. Patients who are known steroid responders (corticosteroid-related intraocular pressure elevation in either eye). 7. Patients who have used topical ocular NSAIDs in the study eye within 15 days prior to Day 0. 8. Patients who have undergone prior intraocular (non-laser) surgery in the study eye within 6 months prior to screening. 9. Patients who have undergone prior intraocular laser surgery in the study eye within 3 months prior to screening. 10. Patients with planned intraocular or laser surgery in the study eye for the duration of the study. 11. Patients with any signs of intraocular inflammation in either eye at screening. 12. Patients with evidence of corneal abnormality or dystrophy (e.g. opacities, guttae,clouding, etc.) or an inability to obtain an acceptable specular micrograph at Screening. 13. Patients with a history of chronic uveitis from any cause in either eye. 14. Patients who have received any prior intravitreal injections in the study eye. 15. Patients with glaucomatous optic neuropathy or glaucomatous visual field loss in either eye. 16. Patients with ocular hypertension with an IOP in the study eye \> 21 mm Hg at Screening with or without treatment with anti-glaucoma monotherapy. 17. Patients with ocular hypertension receiving treatment with two or more anti-glaucoma Medications. 18. Patients treated with any investigational product within 30 days prior to screening or patients enrolled previouslyc study. **Minimum Age:** 40 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Shanghai **Country:** China **Facility:** Shanghai General Hospital #### Overall Officials **Official 1:** **Affiliation:** Ocumension Therapeutics (Shanghai) Co., Ltd **Name:** Zhixun Li **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000007905 - Term: Lens Diseases - ID: D000005128 - Term: Eye Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC11 - Name: Eye Diseases ### Condition Browse Module - Browse Leaves - ID: M10293 - Name: Inflammation - Relevance: HIGH - As Found: Inflammation - ID: M5638 - Name: Cataract - Relevance: HIGH - As Found: Cataract - ID: M17353 - Name: Uveitis - Relevance: LOW - As Found: Unknown - ID: M10917 - Name: Lens Diseases - Relevance: LOW - As Found: Unknown - ID: M8271 - Name: Eye Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002386 - Term: Cataract - ID: D000007249 - Term: Inflammation ### Intervention Browse Module - Browse Branches - Abbrev: Infl - Name: Anti-Inflammatory Agents - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: AnEm - Name: Antiemetics - Abbrev: Gast - Name: Gastrointestinal Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: AnCoag - Name: Anticoagulants - Abbrev: Ot - Name: Other Dietary Supplements ### Intervention Browse Module - Browse Leaves - ID: M7102 - Name: Dexamethasone - Relevance: LOW - As Found: Unknown - ID: M235549 - Name: Dexamethasone acetate - Relevance: LOW - As Found: Unknown - ID: M199152 - Name: BB 1101 - Relevance: LOW - As Found: Unknown - ID: M21320 - Name: Citric Acid - Relevance: LOW - As Found: Unknown - ID: M1837 - Name: Sodium Citrate - Relevance: LOW - As Found: Unknown - ID: T382 - Name: Citrate - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429293 **Brief Title:** Impact of Cognitive Behavioral Therapy on PTSD-CVD Link **Official Title:** Impact of Cognitive Behavioral Therapy on Neural, Inflammatory, & Autonomic Markers in a Sample With PTSD and Cardiovascular Risk: Protocol for a Pilot Randomized Controlled Trial #### Organization Study ID Info **ID:** 2023P001621 #### Organization **Class:** OTHER **Full Name:** Massachusetts General Hospital ### Status Module #### Completion Date **Date:** 2026-07-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2026-07-01 **Type:** ESTIMATED #### Start Date **Date:** 2023-07-01 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Study First Submit Date:** 2024-05-08 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** American Heart Association #### Lead Sponsor **Class:** OTHER **Name:** Massachusetts General Hospital #### Responsible Party **Investigator Affiliation:** Massachusetts General Hospital **Investigator Full Name:** Michael T. Osborne **Investigator Title:** Clinician Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** This is a pilot randomized controlled trial to assess the impact of a first-line treatment for posttraumatic stress disorder (PTSD) (Cognitive Processing Therapy; CPT) versus waitlist control on mechanisms of cardiovascular disease (CVD) risk. Further, this study will test the hypothesis that CPT reduces CVD risk through its effects on inflammation and autonomic function and that these changes are driven by changes in stress-related neural activity (SNA) **Detailed Description:** This study is a randomized controlled trial of CPT compared to waitlist control that is testing the effects of CPT on mechanisms of the PTSD-CVD link. Enrollment began in 2023 and is projected to continue through 2026. Participants include individuals with PTSD and CVD risk recruited from the Boston area (N = 30). Treatment assignment is randomized and stratified by sex. Participants are randomized to CPT (n = 15) or waitlist control (n = 15). Potentially eligible participants complete a screening visit to confirm inclusion/exclusion criteria. Upon confirmation of eligibility, participants are scheduled for a baseline session, where they complete surveys, brain and peripheral imaging, and resting measures of autonomic function. Following the baseline visit, participants are randomized into CPT or the waitlist control group. Those randomized to CPT complete sessions via telehealth. Following a 12-week treatment period, participants attend the post-treatment visit, consisting of the same assessments administered at baseline. Participants randomized to waitlist are offered CPT upon completion of the post-treatment visit. ### Conditions Module **Conditions:** - Posttraumatic Stress Disorder **Keywords:** - Cardiovascular disease - Inflammation - Autonomic function - Stress-related neural activity ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Participants are randomized to 12 weeks of cognitive processing therapy or waitlist control. ##### Masking Info **Masking:** SINGLE **Masking Description:** Individuals who interpret images and data will be blinded to assigned intervention **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 30 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 12 week treatment period of cognitive processing therapy followed by a post-treatment visit. **Intervention Names:** - Behavioral: Cognitive processing therapy **Label:** Cognitive processing therapy **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Participants randomized to waitlist are offered CPT upon completion of the post-treatment visit. **Label:** Control waitlist **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Cognitive processing therapy **Description:** The active intervention is Cognitive Processing Therapy (CPT) is a gold-standard cognitive behavioral therapy for PTSD. The CPT intervention consists of 12 60-minute sessions teaching skills to challenge trauma-relevant cognitions that are distorted or unhelpful. Trauma-relevant cognitions fall into five themes that are highlighted during treatment: safety, trust, power/control, esteem, and intimacy. The empirical base for CPT is strong with numerous studies demonstrating that it results in significant reduction of PTSD symptoms regardless of trauma type and that it is 89% more effective than control treatment. CPT has been successfully implemented in virtual formats with comparable efficacy levels to that of in-person CPT. CPT sessions for this study will be conducted virtually by a CPT-trained clinician **Name:** Cognitive processing therapy **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** Measured via FDG-PET imaging **Measure:** Arterial inflammation **Time Frame:** Baseline and 12-weeks **Description:** Calculated from the average resting HRV collected at baseline and post-treatment visits **Measure:** Heart rate variability **Time Frame:** Baseline and 12-weeks #### Secondary Outcomes **Description:** Measured as bone marrow activity via FDG-PET imaging **Measure:** Leukopoiesis **Time Frame:** Baseline and 12-weeks **Description:** Heart rate in beats per minute **Measure:** Heart rate **Time Frame:** Baseline and 12-weeks **Description:** Systolic and diastolic pressure **Measure:** Blood pressure **Time Frame:** Baseline and 12-weeks **Description:** MRI measurements of atherosclerotic plaque components including necrotic tissue, loose connective tissue, and hemorrhage using black-blood imaging techniques **Measure:** MRI based arterial plaque components (such as necrotic tissue, loose connective tissue, and hemorrhage) **Time Frame:** Baseline and 12-weeks **Description:** Measurements of wall thickness as an assessment of atherosclerotic plaque **Measure:** MRI based arterial wall thickness **Time Frame:** Baseline and 12-weeks **Description:** Structural assessment of brain centers to assess volume and density of neural centers involved in the stress response **Measure:** MRI based brain structure assessments of volume and density **Time Frame:** Baseline and 12-weeks **Description:** Connectivity assessment using mapping on functional MRI at baseline and in response to emotional faces of neural centers involved in the stress response to determine the interplay between neural centers before and after therapy by measuring alterations in blood oxygen content under various conditions in different parts of the brain **Measure:** MRI based brain connectivity (by measuring changes in blood flow across networks of neural centers at rest and with an emotional task) **Time Frame:** Baseline and 12-weeks **Description:** Activation assessment using functional MRI at both rest and in response to emotional faces of neural centers involved in the stress response before and after therapy by measuring blood flow under various conditions to different parts of the brain **Measure:** MRI based brain activation (via measuring blood flow in important neural centers at rest and with an emotional task using functional MRI) **Time Frame:** Baseline and 12-weeks **Description:** Measurement of axonal integrity using diffusion tensor imaging on MRI to determine the strength connections between important brain centers and neural networks related to stress perception in PTSD before and after therapy **Measure:** Axonal integrity of resting neural connections between brain centers using MRI **Time Frame:** Baseline and 12-weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * age 18-65 years (upper limit chosen to optimize changes in brain activation that diminish with age); * criterion A trauma exposure and PTSD symptoms (clinically significant symptoms in at least two symptom clusters); * subclinical atherosclerotic CVD (e.g., coronary, cerebrovascular, or peripheral arterial plaque or calcifications on imaging), clinical atherosclerotic CVD (e.g., myocardial infarction or revascularization), or increased risk for atherosclerotic CVD (i.e., \>2 of hypertension, diabetes mellitus, hyperlipidemia, and active smoking) ability to understand and sign informed consent * fluent English speaker. Exclusion Criteria: * history of stroke, brain surgery, seizure * use of certain CVD medications (e.g., beta-blockers, high-intensity statins \[e.g., rosuvastatin 20/40 mg and atorvastatin 40/80 mg\], PCSK-9 inhibitors); * psychiatric or cardiovascular medication change within 4 weeks (i.e., stable regimen is allowed); * currently in PTSD therapy; * neurological or systemic inflammatory disease/current anti-inflammatory therapy; * moderate/severe alcohol/substance use disorder; * current mania/psychosis; * weight \>300 lbs., claustrophobia, pregnancy, metal implants that are incompatible with magnetic resonance imaging (MRI), or uncontrolled hyperglycemia (for imaging); * significant radiation exposure (\>2 nuclear tests, computed tomography images, or fluoroscopic procedures) for research purposes during the preceding 12-months. **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Michael Osborne, MD **Phone:** 6177261843 **Role:** CONTACT #### Locations **Location 1:** **City:** Boston **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Michael Osborne, MD - **Role:** CONTACT **Country:** United States **Facility:** Massachusetts General Hospital **State:** Massachusetts **Status:** RECRUITING **Zip:** 02114 ### IPD Sharing Statement Module **Access Criteria:** To be determined based on website used **Description:** Deidentified data from primary endpoints and analyses will be made available on a public website following study completion. **IPD Sharing:** YES **Time Frame:** Within 6 months of study completion ### References Module #### References **Citation:** Edmondson D, Cohen BE. Posttraumatic stress disorder and cardiovascular disease. Prog Cardiovasc Dis. 2013 May-Jun;55(6):548-56. doi: 10.1016/j.pcad.2013.03.004. Epub 2013 Apr 6. **PMID:** 23621964 **Citation:** Edmondson D, von Kanel R. Post-traumatic stress disorder and cardiovascular disease. Lancet Psychiatry. 2017 Apr;4(4):320-329. doi: 10.1016/S2215-0366(16)30377-7. Epub 2017 Jan 19. **PMID:** 28109646 **Citation:** Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB. Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry. 1995 Dec;52(12):1048-60. doi: 10.1001/archpsyc.1995.03950240066012. **PMID:** 7492257 **Citation:** Goldstein RB, Smith SM, Chou SP, Saha TD, Jung J, Zhang H, Pickering RP, Ruan WJ, Huang B, Grant BF. The epidemiology of DSM-5 posttraumatic stress disorder in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions-III. Soc Psychiatry Psychiatr Epidemiol. 2016 Aug;51(8):1137-48. doi: 10.1007/s00127-016-1208-5. Epub 2016 Apr 22. **PMID:** 27106853 **Citation:** Ehlers A, Suendermann O, Boellinghaus I, Vossbeck-Elsebusch A, Gamer M, Briddon E, Martin MW, Glucksman E. Heart rate responses to standardized trauma-related pictures in acute posttraumatic stress disorder. Int J Psychophysiol. 2010 Oct;78(1):27-34. doi: 10.1016/j.ijpsycho.2010.04.009. Epub 2010 May 5. **PMID:** 20450940 **Citation:** Jovanovic T, Norrholm SD, Sakoman AJ, Esterajher S, Kozaric-Kovacic D. Altered resting psychophysiology and startle response in Croatian combat veterans with PTSD. Int J Psychophysiol. 2009 Mar;71(3):264-8. doi: 10.1016/j.ijpsycho.2008.10.007. Epub 2008 Nov 5. **PMID:** 19013485 **Citation:** Buckley TC, Kaloupek DG. A meta-analytic examination of basal cardiovascular activity in posttraumatic stress disorder. Psychosom Med. 2001 Jul-Aug;63(4):585-94. doi: 10.1097/00006842-200107000-00011. **PMID:** 11485112 **Citation:** Pan X, Kaminga AC, Wen SW, Liu A. Catecholamines in Post-traumatic Stress Disorder: A Systematic Review and Meta-Analysis. Front Mol Neurosci. 2018 Dec 4;11:450. doi: 10.3389/fnmol.2018.00450. eCollection 2018. **PMID:** 30564100 **Citation:** Brudey C, Park J, Wiaderkiewicz J, Kobayashi I, Mellman TA, Marvar PJ. Autonomic and inflammatory consequences of posttraumatic stress disorder and the link to cardiovascular disease. Am J Physiol Regul Integr Comp Physiol. 2015 Aug 15;309(4):R315-21. doi: 10.1152/ajpregu.00343.2014. Epub 2015 Jun 10. **PMID:** 26062635 **Citation:** Kim TD, Lee S, Yoon S. Inflammation in Post-Traumatic Stress Disorder (PTSD): A Review of Potential Correlates of PTSD with a Neurological Perspective. Antioxidants (Basel). 2020 Jan 26;9(2):107. doi: 10.3390/antiox9020107. **PMID:** 31991875 **Citation:** Schneider M, Schwerdtfeger A. Autonomic dysfunction in posttraumatic stress disorder indexed by heart rate variability: a meta-analysis. Psychol Med. 2020 Sep;50(12):1937-1948. doi: 10.1017/S003329172000207X. Epub 2020 Aug 28. **PMID:** 32854795 **Citation:** Ge F, Yuan M, Li Y, Zhang W. Posttraumatic Stress Disorder and Alterations in Resting Heart Rate Variability: A Systematic Review and Meta-Analysis. Psychiatry Investig. 2020 Jan;17(1):9-20. doi: 10.30773/pi.2019.0112. Epub 2020 Jan 25. **PMID:** 31995968 **Citation:** Moon E, Lee SH, Kim DH, Hwang B. Comparative Study of Heart Rate Variability in Patients with Schizophrenia, Bipolar Disorder, Post-traumatic Stress Disorder, or Major Depressive Disorder. Clin Psychopharmacol Neurosci. 2013 Dec;11(3):137-43. doi: 10.9758/cpn.2013.11.3.137. Epub 2013 Dec 24. **PMID:** 24465250 **Citation:** Seligowski AV, Steuber ER, Hinrichs R, Reda MH, Wiltshire CN, Wanna CP, Winters SJ, Phillips KA, House SL, Beaudoin FL, An X, Stevens JS, Zeng D, Neylan TC, Clifford GD, Linnstaedt SD, Germine LT, Bollen KA, Guffanti G, Rauch SL, Haran JP, Storrow AB, Lewandowski C, Musey PI Jr, Hendry PL, Sheikh S, Jones CW, Punches BE, Kurz MC, Murty VP, McGrath ME, Hudak LA, Pascual JL, Seamon MJ, Datner EM, Chang AM, Pearson C, Peak DA, Merchant RC, Domeier RM, Rathlev NK, O'Neil BJ, Sanchez LD, Bruce SE, Miller MW, Pietrzak RH, Joormann J, Barch DM, Pizzagalli DA, Sheridan JF, Luna B, Harte SE, Elliott JM, Koenen KC, Kessler RC, McLean SA, Ressler KJ, Jovanovic T. A prospective examination of sex differences in posttraumatic autonomic functioning. Neurobiol Stress. 2021 Aug 21;15:100384. doi: 10.1016/j.ynstr.2021.100384. eCollection 2021 Nov. **PMID:** 34485632 **Citation:** Seligowski AV, Grewal SS, Abohashem S, Zureigat H, Qamar I, Aldosoky W, Gharios C, Hanlon E, Alani O, Bollepalli SC, Armoundas A, Fayad ZA, Shin LM, Osborne MT, Tawakol A. PTSD increases risk for major adverse cardiovascular events through neural and cardio-inflammatory pathways. Brain Behav Immun. 2024 Mar;117:149-154. doi: 10.1016/j.bbi.2024.01.006. Epub 2024 Jan 11. **PMID:** 38218349 **Citation:** O'Donovan A, Neylan TC, Metzler T, Cohen BE. Lifetime exposure to traumatic psychological stress is associated with elevated inflammation in the Heart and Soul Study. Brain Behav Immun. 2012 May;26(4):642-9. doi: 10.1016/j.bbi.2012.02.003. Epub 2012 Feb 15. **PMID:** 22366689 **Citation:** Tawakol A, Ishai A, Takx RA, Figueroa AL, Ali A, Kaiser Y, Truong QA, Solomon CJ, Calcagno C, Mani V, Tang CY, Mulder WJ, Murrough JW, Hoffmann U, Nahrendorf M, Shin LM, Fayad ZA, Pitman RK. Relation between resting amygdalar activity and cardiovascular events: a longitudinal and cohort study. Lancet. 2017 Feb 25;389(10071):834-845. doi: 10.1016/S0140-6736(16)31714-7. Epub 2017 Jan 12. Erratum In: Lancet. 2017 Feb 25;389(10071):804. Lancet. 2017 Feb 25;389(10071):804. **PMID:** 28088338 **Citation:** Lima BB, Hammadah M, Wilmot K, Pearce BD, Shah A, Levantsevych O, Kaseer B, Obideen M, Gafeer MM, Kim JH, Sullivan S, Lewis TT, Weng L, Elon L, Li L, Bremner JD, Raggi P, Quyyumi A, Vaccarino V. Posttraumatic stress disorder is associated with enhanced interleukin-6 response to mental stress in subjects with a recent myocardial infarction. Brain Behav Immun. 2019 Jan;75:26-33. doi: 10.1016/j.bbi.2018.08.015. Epub 2018 Aug 30. Erratum In: Brain Behav Immun. 2019 May;78:204-205. **PMID:** 30172946 **Citation:** Myers B. Corticolimbic regulation of cardiovascular responses to stress. Physiol Behav. 2017 Apr 1;172:49-59. doi: 10.1016/j.physbeh.2016.10.015. Epub 2016 Oct 25. **PMID:** 27793557 **Citation:** Shin LM, Orr SP, Carson MA, Rauch SL, Macklin ML, Lasko NB, Peters PM, Metzger LJ, Dougherty DD, Cannistraro PA, Alpert NM, Fischman AJ, Pitman RK. Regional cerebral blood flow in the amygdala and medial prefrontal cortex during traumatic imagery in male and female Vietnam veterans with PTSD. Arch Gen Psychiatry. 2004 Feb;61(2):168-76. doi: 10.1001/archpsyc.61.2.168. **PMID:** 14757593 **Citation:** Shin LM, Wright CI, Cannistraro PA, Wedig MM, McMullin K, Martis B, Macklin ML, Lasko NB, Cavanagh SR, Krangel TS, Orr SP, Pitman RK, Whalen PJ, Rauch SL. A functional magnetic resonance imaging study of amygdala and medial prefrontal cortex responses to overtly presented fearful faces in posttraumatic stress disorder. Arch Gen Psychiatry. 2005 Mar;62(3):273-81. doi: 10.1001/archpsyc.62.3.273. **PMID:** 15753240 **Citation:** Williams LM, Kemp AH, Felmingham K, Barton M, Olivieri G, Peduto A, Gordon E, Bryant RA. Trauma modulates amygdala and medial prefrontal responses to consciously attended fear. Neuroimage. 2006 Jan 15;29(2):347-57. doi: 10.1016/j.neuroimage.2005.03.047. Epub 2005 Oct 10. **PMID:** 16216534 **Citation:** Stevens JS, Jovanovic T, Fani N, Ely TD, Glover EM, Bradley B, Ressler KJ. Disrupted amygdala-prefrontal functional connectivity in civilian women with posttraumatic stress disorder. J Psychiatr Res. 2013 Oct;47(10):1469-78. doi: 10.1016/j.jpsychires.2013.05.031. Epub 2013 Jul 1. **PMID:** 23827769 **Citation:** Osborne MT, Abohashem S, Zureigat H, Abbasi TA, Tawakol A. Multimodality molecular imaging: Gaining insights into the mechanisms linking chronic stress to cardiovascular disease. J Nucl Cardiol. 2021 Jun;28(3):955-966. doi: 10.1007/s12350-020-02424-6. Epub 2020 Nov 17. **PMID:** 33205328 **Citation:** Manthey A, Sierk A, Brakemeier EL, Walter H, Daniels JK. Does trauma-focused psychotherapy change the brain? A systematic review of neural correlates of therapeutic gains in PTSD. Eur J Psychotraumatol. 2021 Aug 6;12(1):1929025. doi: 10.1080/20008198.2021.1929025. eCollection 2021. **PMID:** 34394855 **Citation:** Aupperle RL, Allard CB, Simmons AN, Flagan T, Thorp SR, Norman SB, Paulus MP, Stein MB. Neural responses during emotional processing before and after cognitive trauma therapy for battered women. Psychiatry Res. 2013 Oct 30;214(1):48-55. doi: 10.1016/j.pscychresns.2013.05.001. Epub 2013 Aug 2. **PMID:** 23916537 **Citation:** Santarnecchi E, Bossini L, Vatti G, Fagiolini A, La Porta P, Di Lorenzo G, Siracusano A, Rossi S, Rossi A. Psychological and Brain Connectivity Changes Following Trauma-Focused CBT and EMDR Treatment in Single-Episode PTSD Patients. Front Psychol. 2019 Feb 25;10:129. doi: 10.3389/fpsyg.2019.00129. eCollection 2019. **PMID:** 30858808 **Citation:** Helpman L, Marin MF, Papini S, Zhu X, Sullivan GM, Schneier F, Neria M, Shvil E, Malaga Aragon MJ, Markowitz JC, Lindquist MA, Wager T, Milad M, Neria Y. Neural changes in extinction recall following prolonged exposure treatment for PTSD: A longitudinal fMRI study. Neuroimage Clin. 2016 Oct 10;12:715-723. doi: 10.1016/j.nicl.2016.10.007. eCollection 2016. **PMID:** 27761402 **Citation:** Zhu X, Suarez-Jimenez B, Lazarov A, Helpman L, Papini S, Lowell A, Durosky A, Lindquist MA, Markowitz JC, Schneier F, Wager TD, Neria Y. Exposure-based therapy changes amygdala and hippocampus resting-state functional connectivity in patients with posttraumatic stress disorder. Depress Anxiety. 2018 Oct;35(10):974-984. doi: 10.1002/da.22816. Epub 2018 Sep 10. **PMID:** 30260530 **Citation:** Abdallah CG, Averill CL, Ramage AE, Averill LA, Alkin E, Nemati S, Krystal JH, Roache JD, Resick P, Young-McCaughan S, Peterson AL, Fox P; STRONG STAR Consortium. Reduced Salience and Enhanced Central Executive Connectivity Following PTSD Treatment. Chronic Stress (Thousand Oaks). 2019 Jan-Feb;3:2470547019838971. doi: 10.1177/2470547019838971. Epub 2019 Apr 15. **PMID:** 31008419 **Citation:** Watkins LL, LoSavio ST, Calhoun P, Resick PA, Sherwood A, Coffman CJ, Kirby AC, Beaver TA, Dennis MF, Beckham JC. Effect of cognitive processing therapy on markers of cardiovascular risk in posttraumatic stress disorder patients: A randomized clinical trial. J Psychosom Res. 2023 Jul;170:111351. doi: 10.1016/j.jpsychores.2023.111351. Epub 2023 May 2. **PMID:** 37178469 **Citation:** Weathers FW, Bovin MJ, Lee DJ, Sloan DM, Schnurr PP, Kaloupek DG, Keane TM, Marx BP. The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5): Development and initial psychometric evaluation in military veterans. Psychol Assess. 2018 Mar;30(3):383-395. doi: 10.1037/pas0000486. Epub 2017 May 11. **PMID:** 28493729 **Citation:** Radfar A, Abohashem S, Osborne MT, Wang Y, Dar T, Hassan MZO, Ghoneem A, Naddaf N, Patrich T, Abbasi T, Zureigat H, Jaffer J, Ghazi P, Scott JA, Shin LM, Pitman RK, Neilan TG, Wood MJ, Tawakol A. Stress-associated neurobiological activity associates with the risk for and timing of subsequent Takotsubo syndrome. Eur Heart J. 2021 May 14;42(19):1898-1908. doi: 10.1093/eurheartj/ehab029. **PMID:** 33768230 **Citation:** Emami H, Singh P, MacNabb M, Vucic E, Lavender Z, Rudd JH, Fayad ZA, Lehrer-Graiwer J, Korsgren M, Figueroa AL, Fredrickson J, Rubin B, Hoffmann U, Truong QA, Min JK, Baruch A, Nasir K, Nahrendorf M, Tawakol A. Splenic metabolic activity predicts risk of future cardiovascular events: demonstration of a cardiosplenic axis in humans. JACC Cardiovasc Imaging. 2015 Feb;8(2):121-30. doi: 10.1016/j.jcmg.2014.10.009. Epub 2015 Jan 7. **PMID:** 25577441 **Citation:** Hariri AR, Bookheimer SY, Mazziotta JC. Modulating emotional responses: effects of a neocortical network on the limbic system. Neuroreport. 2000 Jan 17;11(1):43-8. doi: 10.1097/00001756-200001170-00009. **PMID:** 10683827 **Citation:** Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation. 1996 Mar 1;93(5):1043-65. No abstract available. **PMID:** 8598068 **Citation:** Asmundson GJG, Thorisdottir AS, Roden-Foreman JW, Baird SO, Witcraft SM, Stein AT, Smits JAJ, Powers MB. A meta-analytic review of cognitive processing therapy for adults with posttraumatic stress disorder. Cogn Behav Ther. 2019 Jan;48(1):1-14. doi: 10.1080/16506073.2018.1522371. Epub 2018 Oct 18. **PMID:** 30332919 **Citation:** Kline AC, Cooper AA, Rytwinksi NK, Feeny NC. Long-term efficacy of psychotherapy for posttraumatic stress disorder: A meta-analysis of randomized controlled trials. Clin Psychol Rev. 2018 Feb;59:30-40. doi: 10.1016/j.cpr.2017.10.009. Epub 2017 Nov 21. **PMID:** 29169664 **Citation:** Watts BV, Schnurr PP, Mayo L, Young-Xu Y, Weeks WB, Friedman MJ. Meta-analysis of the efficacy of treatments for posttraumatic stress disorder. J Clin Psychiatry. 2013 Jun;74(6):e541-50. doi: 10.4088/JCP.12r08225. **PMID:** 23842024 **Citation:** Held P, Kovacevic M, Petrey K, Meade EA, Pridgen S, Montes M, Werner B, Miller ML, Smith DL, Kaysen D, Karnik NS. Treating posttraumatic stress disorder at home in a single week using 1-week virtual massed cognitive processing therapy. J Trauma Stress. 2022 Aug;35(4):1215-1225. doi: 10.1002/jts.22831. Epub 2022 Mar 25. **PMID:** 35338534 **Citation:** Held P, Coleman JA, Petrey K, Klassen BJ, Pridgen S, Bravo K, Smith DL, Van Horn R. A case series examining PTSD and depression symptom reductions over the course of a 2-week virtual intensive PTSD treatment program for veterans. Psychol Trauma. 2022 May;14(4):615-623. doi: 10.1037/tra0001106. Epub 2021 Aug 26. **PMID:** 34435816 **Citation:** Tawakol A, Fayad ZA, Mogg R, Alon A, Klimas MT, Dansky H, Subramanian SS, Abdelbaky A, Rudd JH, Farkouh ME, Nunes IO, Beals CR, Shankar SS. Intensification of statin therapy results in a rapid reduction in atherosclerotic inflammation: results of a multicenter fluorodeoxyglucose-positron emission tomography/computed tomography feasibility study. J Am Coll Cardiol. 2013 Sep 3;62(10):909-17. doi: 10.1016/j.jacc.2013.04.066. Epub 2013 May 30. **PMID:** 23727083 **Citation:** Bourassa KJ, Hendrickson RC, Reger GM, Norr AM. Posttraumatic Stress Disorder Treatment Effects on Cardiovascular Physiology: A Systematic Review and Agenda for Future Research. J Trauma Stress. 2021 Apr;34(2):384-393. doi: 10.1002/jts.22637. Epub 2020 Dec 5. **PMID:** 33277952 **Citation:** Gan WQ, Buxton JA, Scheuermeyer FX, Palis H, Zhao B, Desai R, Janjua NZ, Slaunwhite AK. Risk of cardiovascular diseases in relation to substance use disorders. Drug Alcohol Depend. 2021 Dec 1;229(Pt A):109132. doi: 10.1016/j.drugalcdep.2021.109132. Epub 2021 Oct 27. **PMID:** 34768052 **Citation:** Byers AL, Covinsky KE, Neylan TC, Yaffe K. Chronicity of posttraumatic stress disorder and risk of disability in older persons. JAMA Psychiatry. 2014 May;71(5):540-6. doi: 10.1001/jamapsychiatry.2014.5. **PMID:** 24647756 **Citation:** Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM, Chang AR, Cheng S, Das SR, Delling FN, Djousse L, Elkind MSV, Ferguson JF, Fornage M, Jordan LC, Khan SS, Kissela BM, Knutson KL, Kwan TW, Lackland DT, Lewis TT, Lichtman JH, Longenecker CT, Loop MS, Lutsey PL, Martin SS, Matsushita K, Moran AE, Mussolino ME, O'Flaherty M, Pandey A, Perak AM, Rosamond WD, Roth GA, Sampson UKA, Satou GM, Schroeder EB, Shah SH, Spartano NL, Stokes A, Tirschwell DL, Tsao CW, Turakhia MP, VanWagner LB, Wilkins JT, Wong SS, Virani SS; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2019 Update: A Report From the American Heart Association. Circulation. 2019 Mar 5;139(10):e56-e528. doi: 10.1161/CIR.0000000000000659. No abstract available. Erratum In: Circulation. 2020 Jan 14;141(2):e33. **PMID:** 30700139 #### See Also Links **Label:** About Multiple Cause of Death **URL:** https://wonder.cdc.gov/mcd-icd10.html **Label:** The Life Events Checklist for DSM-5 (LEC-5) **URL:** https://www.ptsd.va.gov/professional/assessment/te-measures/life_events_checklist.asp **Label:** The PTSD checklist for DSM-5 (PCL-5) **URL:** https://www.ptsd.va.gov/professional/assessment/adult-sr/ptsd-checklist.asp ## Derived Section ### Condition Browse Module - Ancestors - ID: D000040921 - Term: Stress Disorders, Traumatic - ID: D000068099 - Term: Trauma and Stressor Related Disorders - ID: D000001523 - Term: Mental Disorders ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: BC26 - Name: Wounds and Injuries ### Condition Browse Module - Browse Leaves - ID: M10293 - Name: Inflammation - Relevance: LOW - As Found: Unknown - ID: M16103 - Name: Stress Disorders, Post-Traumatic - Relevance: HIGH - As Found: Posttraumatic Stress Disorder - ID: M24916 - Name: Stress Disorders, Traumatic - Relevance: LOW - As Found: Unknown - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown - ID: M222 - Name: Trauma and Stressor Related Disorders - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000013313 - Term: Stress Disorders, Post-Traumatic ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429280 **Brief Title:** Clinical Data Registry of Amblyopia Patients on Luminopia Treatment **Official Title:** Clinical Data Registry of Amblyopia Patients on Luminopia Treatment #### Organization Study ID Info **ID:** R-AM-1 #### Organization **Class:** INDUSTRY **Full Name:** Luminopia ### Status Module #### Completion Date **Date:** 2026-12-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2026-04-01 **Type:** ESTIMATED #### Start Date **Date:** 2023-09-01 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Study First Submit Date:** 2024-02-23 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Luminopia #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Amblyopia is the most prevalent cause of reduced monocular visual acuity in children and young adults, with estimates of prevalence ranging from 1% to 5%. The most common associated amblyogenic risk factors are uncorrected anisometropia, strabismus, or a combination of these. In addition to reduced visual acuity, amblyopic patients may also have measurable dysfunction of accommodation, fixation, binocularity, vergence, reading fluency, depth perception, and contrast sensitivity. For the first time since the incorporation of atropine penalization into amblyopia management, physicians can now offer Luminopia, an FDA-approved dual action dichoptic treatment, to patients with amblyopia. Since the product became commercially available in November 2022, the number of patients on Luminopia therapy continues to grow. This presents a unique opportunity to gather real world evidence from a large number of patients, representative of how ophthalmologists and optometrists are applying this novel treatment in the real world. A registry of the clinical data associated with Luminopia treatment, with IRB oversight, will provide answers to key scientific questions using a large dataset. ### Conditions Module **Conditions:** - Amblyopia ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** RETROSPECTIVE #### Enrollment Info **Count:** 500 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Description:** Medical Device which treats unilateral amblyopia through therapeutic software which stimulate vision **Name:** N/A this is an observational study of Standard of Care **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Change in Visual Acuity from baseline to consecutive visits **Measure:** Change in Visual Acuity from baseline to consecutive visits **Time Frame:** 3, 6,12, 24 months **Description:** Duration of Visual Acuity treatment and number of follow-up visits **Measure:** Duration of Visual Acuity treatment and number of follow-up visits **Time Frame:** 3, 6,12, 24 months **Description:** Durability of Visual Acuity results post-treatment cessation **Measure:** Durability of Visual Acuity results post-treatment cessation **Time Frame:** 3, 6,12, 24 months **Description:** Adherence with Luminopia treatment **Measure:** Adherence with Luminopia treatment **Time Frame:** 3, 6,12, 24 months **Description:** Change in Stereoacuity from baseline to consecutive visits **Measure:** Change in Stereoacuity from baseline to consecutive visits **Time Frame:** 3, 6,12, 24 months #### Secondary Outcomes **Description:** Visual Acuity analyses will also be conducted by Prior Treatment **Measure:** Visual Acuity analyses will also be conducted by Prior Treatment **Time Frame:** 3, 6,12, 24 months **Description:** Visual Acuity analyses will also be conducted by Amblyopia Type **Measure:** Visual Acuity analyses will also be conducted by Amblyopia Type **Time Frame:** 3, 6,12, 24 months **Description:** Visual Acuity Analyses will also be conducted by Age **Measure:** Visual Acuity Analyses will also be conducted by Age **Time Frame:** 3, 6,12, 24 months **Description:** Visual Acuity analyses will also be conducted by Baseline Angle of Deviation **Measure:** Visual Acuity analyses will also be conducted by Baseline Angle of Deviation **Time Frame:** 3, 6,12, 24 months **Description:** Visual Acuity analyses will also be conducted by Severity (Baseline Visual Acuity) **Measure:** Visual Acuity analyses will also be conducted by Severity (Baseline Visual Acuity) **Time Frame:** 3, 6,12, 24 months **Description:** Visual Acuity analyses will also be conducted by Adherence to Treatment **Measure:** Visual Acuity analyses will also be conducted by Adherence to Treatment **Time Frame:** 3, 6,12, 24 months **Description:** Visual Acuity Analyses will also be conducted by Prescribed Dose **Measure:** Visual Acuity Analyses will also be conducted by Prescribed Dose **Time Frame:** 3, 6,12, 24 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Have a diagnosis of amblyopia * Have undergone or currently undergoing Luminopia treatment for a minimum of 12 weeks Exclusion Criteria: -Have participated in prior Luminopia clinical trials **Sampling Method:** PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT **Study Population:** Patients with a diagnosis of Amblyopia ### Contacts Locations Module #### Locations **Location 1:** **City:** San Ramon **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Endri Angjeli - **Phone:** 978-806-7080 - **Role:** CONTACT **Country:** United States **Facility:** UCSF Benioff Children's Physicians **State:** California **Status:** RECRUITING **Zip:** 94583 **Location 2:** **City:** Santa Barbara **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Endri Angjeli - **Phone:** 978-806-7080 - **Role:** CONTACT **Country:** United States **Facility:** Sansum Clinic **State:** California **Status:** RECRUITING **Zip:** 93110 **Location 3:** **City:** Crestview **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Endri Angjeli - **Phone:** 978-806-7080 - **Role:** CONTACT **Country:** United States **Facility:** Okaloosa Ophthalmology **State:** Florida **Status:** RECRUITING **Zip:** 32536 **Location 4:** **City:** Gainesville **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Endri Angjeli - **Phone:** 978-806-7080 - **Role:** CONTACT **Country:** United States **Facility:** Family Focus Eye Care **State:** Florida **Status:** RECRUITING **Zip:** 32605 **Location 5:** **City:** Maitland **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Endri Angjeli - **Phone:** 978-806-7080 - **Role:** CONTACT ***Contact 2:*** - **Name:** Louis Blumenfeld - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** Eye Physicians of Central Florida **State:** Florida **Status:** RECRUITING **Zip:** 32751 **Location 6:** **City:** Savannah **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Endri Angjeli - **Phone:** 978-806-7080 - **Role:** CONTACT **Country:** United States **Facility:** Children's Eye Institute of Savannah **State:** Georgia **Status:** RECRUITING **Zip:** 31406 **Location 7:** **City:** Honolulu **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Endri Angjeli - **Phone:** 978-806-7080 - **Role:** CONTACT **Country:** United States **Facility:** Honolulu Eye Clinic **State:** Hawaii **Status:** RECRUITING **Zip:** 96813 **Location 8:** **City:** Chicago **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Endri Angjeli - **Phone:** 978-806-7080 - **Role:** CONTACT **Country:** United States **Facility:** Lurie Children's Hospital **State:** Illinois **Status:** RECRUITING **Zip:** 60611 **Location 9:** **City:** Indianapolis **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Endri Angjeli - **Phone:** 978-806-7080 - **Role:** CONTACT **Country:** United States **Facility:** Riley Children's Hospital at IU Health **State:** Indiana **Status:** RECRUITING **Zip:** 46202 **Location 10:** **City:** Las Vegas **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Endri Angjeli - **Phone:** 978-806-7080 - **Role:** CONTACT **Country:** United States **Facility:** Nevada Eye Physicians **State:** Nevada **Status:** RECRUITING **Zip:** 89149 **Location 11:** **City:** Concord **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Endri Angjeli - **Phone:** 978-806-7080 - **Role:** CONTACT **Country:** United States **Facility:** Concord Eye Center **State:** New Hampshire **Status:** RECRUITING **Zip:** 03301 **Location 12:** **City:** Philadelphia **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Endri Angjeli - **Phone:** 978-806-7080 - **Role:** CONTACT **Country:** United States **Facility:** Children's Hospital Of Philadelphia **State:** Pennsylvania **Status:** RECRUITING **Zip:** 19104 **Location 13:** **City:** Fort Worth **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Endri Angjeli - **Phone:** 978-806-7080 - **Role:** CONTACT **Country:** United States **Facility:** Pediatric Eye Specialist **State:** Texas **Status:** RECRUITING **Zip:** 76104 ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000014786 - Term: Vision Disorders - ID: D000012678 - Term: Sensation Disorders - ID: D000009461 - Term: Neurologic Manifestations - ID: D000005128 - Term: Eye Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC11 - Name: Eye Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M3891 - Name: Amblyopia - Relevance: HIGH - As Found: Amblyopia - ID: M5204 - Name: Brain Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M17530 - Name: Vision Disorders - Relevance: LOW - As Found: Unknown - ID: M15490 - Name: Sensation Disorders - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: M8271 - Name: Eye Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000000550 - Term: Amblyopia ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429267 **Brief Title:** Investigation Of Bioabsorbable Screws In Pediatric Orthopedic Surgery **Official Title:** Comprehensive Investigation of Bioabsorbable Screws in Pediatric Orthopedic Surgery: Mechanical Properties, Long-term Performance, and Practical Applications #### Organization Study ID Info **ID:** 6360 #### Organization **Class:** OTHER **Full Name:** Louisiana State University Health Sciences Center in New Orleans ### Status Module #### Completion Date **Date:** 2026-04 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2026-04 **Type:** ESTIMATED #### Start Date **Date:** 2024-02-26 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Study First Submit Date:** 2024-05-01 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Louisiana State University Health Sciences Center in New Orleans #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** True **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** This study is a prospective randomized controlled trial comparing the clinical outcomes of bioabsorbable screws to conventional metal screws in pediatric patients (aged 0 to 18) undergoing surgical fixation for trauma or elective procedures. Conducted by the pediatric orthopedic department at Children's Hospital New Orleans, the study aims to evaluate the effectiveness of these screws in bone healing over key post-operative intervals (6 weeks, 6 months, and 1 year). It seeks to determine if bioabsorbable screws offer significant advantages over metal screws in terms of reducing the need for secondary surgeries, based on their hypothesized noninferiority in complication rates. Participants will be randomly assigned to receive either bioabsorbable or metal (titanium or stainless steel) screws after obtaining informed consent from a parent or guardian. **Detailed Description:** This study is a prospective randomized controlled trial to evaluate clinical outcomes associated with the use of bioabsorbable screws compared to conventional metal screws in children aged 0 to 18 who are undergoing surgical fixation in the setting of trauma such as medial epicondyle fractures of the elbow or elective procedures. The research will be conducted within the pediatric orthopedic department at CHNOLA, and participants will be assessed at key intervals, including 6 weeks, 6 months, and 1 year post-operation post-operation. The primary objective of this study is to assess and compare the effectiveness of conventional metal screws and bioabsorbable screws in bone healing. This study aims to determine whether bioabsorbable screws are significantly superior to conventional titanium screws. The investigators hypothesize bioabsorbable screws are significantly noninferior to conventional metal screws in terms of complications based on prior surgical constructs that demonstrate bioabsorbable screws eliminate the need for a second surgery After informed consent has been obtained from the parents of patients, eligible patients undergoing cannulated screw fixation will be randomized into two groups: one group who will receive bioabsorbable screws and the other group who will receive metal screws (titanium or stainless steel). ### Conditions Module **Conditions:** - Pediatric - Fracture - Orthopedic Devices Associated With Misadventures, Surgical Instruments, Materials and Devices (Including Sutures) - Patient Satisfaction ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Participants will be randomized to one of two groups which will determine the type of screw (stainless steel or bioabsorbable) in their surgery. ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 60 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients that are randomly assigned to receive traditional, metal screws **Intervention Names:** - Device: Metal/Titanium Screw **Label:** Control Group (Receiving Metal Screws) **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Patients that are randomly assigned to receive Bioabsorbable screws **Intervention Names:** - Device: Bioabsorbable Screw **Label:** Experimental Group (Receiving Bioabsorbable Screws) **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Experimental Group (Receiving Bioabsorbable Screws) **Description:** Bioabsorbable screw that redissolves into the bone. Mineral fibers are composed of Silicon Dioxide (SiO2), Sodium Oxide, Calcium Oxide, Magnesium Oxide, Boron Trioxide, and Phosphorous Pentoxide **Name:** Bioabsorbable Screw **Other Names:** - Ossiofiber **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - Control Group (Receiving Metal Screws) **Description:** Traditional metal screw used in fracture fixation that requires hardware removal **Name:** Metal/Titanium Screw **Other Names:** - OrthoPediatrics **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Pain, Upper Extremity and Mobility. These questionnaires are scored using T scores. For pain, a higher score is a worse outcome. For mobility and upper extremity, a lower score is a worse outcome. Min value is 0 and max is 100 for all. **Measure:** Computer Adaptive PROMIS (Patient-Reported Outcomes Measurement Information System) Surveys **Time Frame:** 6 weeks, 6 months, 1 year #### Secondary Outcomes **Description:** Any complications of surgery (infection etc) **Measure:** Complications **Time Frame:** 1 year ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Primary fractures requiring fixation with cannulated screws Exclusion Criteria: * Children ten years old or under with a fracture requiring screws to be fixed across the growth plate (physis) * Secondary fractures * Non-union fractures * Tibial tubercle osteotomies (TTOs) * Slipped capital femoral epiphysis (SCFEs) * Unable or unwilling to provide informed consent or parental/guardian consent for participants under 18 years of age * Allergies or contraindications to screw materials **Healthy Volunteers:** True **Maximum Age:** 18 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Sylvia Culpepper, MS **Phone:** 2283270278 **Role:** CONTACT **Contact 2:** **Name:** Carter Clement, MD, MBA **Phone:** (504) 896-9569 **Role:** CONTACT #### Locations **Location 1:** **City:** New Orleans **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Sylvia Culpepper, MS - **Phone:** 228-327-0278 - **Role:** CONTACT ***Contact 2:*** - **Name:** Carter Clement, MD, MBA - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 3:*** - **Name:** Sylvia Culpepper, MS - **Role:** SUB_INVESTIGATOR **Country:** United States **Facility:** Children's Hospital New Orleans **State:** Louisiana **Status:** RECRUITING **Zip:** 70118 #### Overall Officials **Official 1:** **Affiliation:** LSUHSC **Name:** Carter Clement, MD, MBA **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Description:** all IPD that underlie results in a publication **IPD Sharing:** YES ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M26370 - Name: Fractures, Bone - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Gast - Name: Gastrointestinal Agents - Abbrev: BDCA - Name: Bone Density Conservation Agents - Abbrev: Micro - Name: Micronutrients ### Intervention Browse Module - Browse Leaves - ID: M5381 - Name: Calcium - Relevance: LOW - As Found: Unknown - ID: M11269 - Name: Magnesium Oxide - Relevance: LOW - As Found: Unknown - ID: M5398 - Name: Calcium, Dietary - Relevance: LOW - As Found: Unknown - ID: M15630 - Name: Silicon - Relevance: LOW - As Found: Unknown - ID: M5173 - Name: Boron - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429254 **Brief Title:** The Effect of Emotional Freedom Techniques on Pelvic Pain **Official Title:** Effect of Emotional Freedom Techniques on Pelvic Pain and Quality of Life in Women With Endometriosis: A Randomized Controlled Study #### Organization Study ID Info **ID:** 01/05 #### Organization **Class:** OTHER **Full Name:** Karabuk University ### Status Module #### Completion Date **Date:** 2024-10-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-24 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-09-01 **Type:** ESTIMATED #### Start Date **Date:** 2024-05-24 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Study First Submit Date:** 2024-04-27 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Karabuk University #### Responsible Party **Investigator Affiliation:** Karabuk University **Investigator Full Name:** Ayse Cuvadar **Investigator Title:** Assistant Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Pelvic pain caused by endometriosis is a common symptom and reduces women's quality of life. EFT is a method that can be preferred in pelvic pain due to its ease of use and low cost. Raising women's awareness for EFT **Detailed Description:** Pelvic pain caused by endometriosis is a common symptom and reduces women's quality of life. EFT has become widely used in medical and psychological treatment settings in recent years.It is also used as a self-help technique by millions of people every year.EFT is a method that can be preferred in pelvic pain due to its ease of use and low cost. ### Conditions Module **Conditions:** - Woman - Pelvic Pain **Keywords:** - Pelvic pain - Woman - quality of life ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - PARTICIPANT **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 64 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** First, the Personal Information Form, Visual Analogue Scale, and Quality of Life Scale will be administered as pre-tests to the EFT group. A high score obtained from the quality of life scale indicates a high quality of life. After the pre-tests, the first EFT session will be conducted. A second EFT session will take place 30 days later, followed by post-tests. During this period, affirmations will be provided as needed based on individual difficulties, perspectives, support systems, past traumas, and emotional blockages experienced by the woman. Each session is planned to last approximately 45 minutes to 1 hour. Procedure: Administering pre-tests followed by the first EFT session. Procedure: After 30 days, conducting post-tests followed by the second EFT session. Procedure: After another 30 days, only post-tests will be conducted. **Intervention Names:** - Other: Experimental group **Label:** Emotional Freedom Techniques group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** After obtaining consent from the women included in the group, pre-tests will be conducted followed by breathing exercises. A program will be tailored according to the suitability of the women. Once an appropriate environment is provided for meeting with the women, information about the study will be provided. Pain coping methods will be explained, and breathing exercises will be taught. The exercises will commence when the woman feels ready. The breathing exercises typically last around 15-20 minutes. With a plan for a total of 8 breathing exercises to be conducted over four weeks, consisting of 2 sessions per week, they will be scheduled to coincide with the EFT group, with sessions held every 5 days. **Label:** Control group **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Emotional Freedom Techniques group **Description:** Life Scale will be administered as pre-tests to the EFT group. After the pre-tests, the first EFT session will be conducted. A second EFT session will take place 30 days later, followed by post-tests. During this period, affirmations will be provided as needed based on individual difficulties, perspectives, support systems, past traumas, and emotional blockages experienced by the woman. Each session is planned to last approximately 45 minutes to 1 hour. **Name:** Experimental group **Other Names:** - EFT group **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Emotional Freedom Techniques **Measure:** Examining the Effect of Emotional Freedom Technique on Pelvic Pain İn Endometriosis **Time Frame:** 1 time per month up to 2 months, Pain will be assessed using the VAS (Visual Analogue Scale). A high score on the scale indicates high pain. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Being diagnosed with endometriosis 2. Experiencing pelvic pain 3. Being between the ages of 18-49 4. Those whose symptom complaints are 5 or above on the visual analogue scale Exclusion Criteria: 1. Patients with known systemic diseases (e.g. hypertension, diabetes, coronary, kidney and liver diseases); 2. Patients with known malignancy; 3. Women in menopause; 4. Having any obstacle to communication **Gender Based:** True **Gender Description:** Women **Healthy Volunteers:** True **Maximum Age:** 49 Years **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Edirne **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Ayşe Çuvadar - **Phone:** 05536217689 - **Role:** CONTACT **Country:** Turkey **Facility:** Trakya University **Status:** RECRUITING **Zip:** 22100 **Location 2:** **City:** Edirne **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Ayşe Çuvadar - **Phone:** 05536217689 - **Role:** CONTACT ***Contact 2:*** - **Name:** Zuhal Guksu - **Role:** SUB_INVESTIGATOR **Country:** Turkey **Facility:** Trakya University **Status:** RECRUITING **Zip:** 22100 ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010146 - Term: Pain - ID: D000009461 - Term: Neurologic Manifestations ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BXM - Name: Behaviors and Mental Disorders ### Condition Browse Module - Browse Leaves - ID: M19918 - Name: Pelvic Pain - Relevance: HIGH - As Found: Pelvic Pain - ID: M7877 - Name: Endometriosis - Relevance: LOW - As Found: Unknown - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: T6034 - Name: Quality of Life - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000017699 - Term: Pelvic Pain ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429241 **Brief Title:** Evaluate the Distribution and Dynamic Behavior of TH-SC01 Cells in Vivo in Patients With Perianal Fistula **Official Title:** A Phase I Clinical Study Evaluating the Distribution and Dynamic Behavior of Nuclide Labeled TH-SC01 Cells in Vivo in Patients With Perianal Fistula #### Organization Study ID Info **ID:** 2023-TH-SC01-I-007 #### Organization **Class:** INDUSTRY **Full Name:** Jiangsu Topcel-KH Pharmaceutical Co., Ltd. ### Status Module #### Completion Date **Date:** 2025-12 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2024-11 **Type:** ESTIMATED #### Start Date **Date:** 2024-06 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Study First Submit Date:** 2024-05-09 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** The First Affiliated Hospital of Soochow University #### Lead Sponsor **Class:** INDUSTRY **Name:** Jiangsu Topcel-KH Pharmaceutical Co., Ltd. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to evaluate the distribution and dynamic behavior of Nuclide labeled TH-SC01 cells in vivo in patients with perianal fistula **Detailed Description:** A Phase I clinical study evaluating the distribution and dynamic behavior of Nuclide labeled TH-SC01 cells in vivo in patients with perianal fistula ### Conditions Module **Conditions:** - Anal Fistula - Complex Perianal Fistulas - Crohn's Disease ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 8 **Type:** ESTIMATED **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Intralesional injection of expanded human umbilical cord-derived mesenchymal stem cells suspension. **Intervention Names:** - Biological: Mesenchymal Stem Cells (MSCs) **Label:** MSCs treatment group **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - MSCs treatment group **Description:** single dose injection (120 million cells) **Name:** Mesenchymal Stem Cells (MSCs) **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Description:** Standardized values of organs or tissues after PET/CT imaging after local injection in patients with perianal fistula **Measure:** Standardized uptake value **Time Frame:** 8-12 hour、32-36 hour、56-60 hour、104-108 hour、152-156 hour，296-300 hour #### Secondary Outcomes **Description:** Change from baseline in pain score (VAS score).Total score ranges from 0 to 10. Higher score means more pain. **Measure:** Effectiveness endpoint:Proportion of subjects with clinically significant effect at week 24 after local injection **Time Frame:** Week 1，Week 4，Week 24 **Description:** All subjects were observed for any adverse events/reactions or serious adverse events/reactions that occurred during the clinical trial, including but not limited to clinically significant abnormal changes in clinical symptoms, physical examination, vital signs examination, laboratory examination, 12-lead electrocardiogram examination, etc. The clinical features, severity, occurrence time, end time, treatment and outcome of the disease should be recorded, and the correlation between the disease and the investigational drug should be determined. **Measure:** Safety endpoint: Treatment-related adverse events/adverse reactions, serious adverse events/serious adverse events **Time Frame:** Week 1，Week 4，Week 24，Month 24 **Description:** Based on the image data obtained by PET/CT scan, OLINDA's sphere model was used to delineate the injection site and important organs or tissues as areas of interest (ROI), obtain standardized uptake values (SUV) of each ROI, and obtain time-radioactive activity curves (TACs) of each tissue and organ. The absorbed dose of vital organs or tissues, the equivalent dose of the whole body, and the distribution and change of transplanted cells in different tissues or organs at different time points are described **Measure:** Radiation exposure: Uptake rate (%ID), absorbed dose, and systemic effective dose in vital organs or tissues after local injection of nuclide labeled TH-SC01 cells. **Time Frame:** Week 1 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Signed informed consent 2. Subjects with Crohn\&amp;#39;s disease or complex perianal fistula diagnosed at least 6 months earlier according to the Chinese Consensus Opinion on the Diagnosis and Treatment of Inflammatory Bowel Diseases (Beijing, 2018).Subjects with active perianal fistula and non active luminal CD defined by a CDAI ≤ 200. 3. For patients with perianal fistula, 1≤ the number of internal openings ≤2, and 1≤ the number of external openings ≤3, the fistula of the patient needs to be drained smoothly 4. All subjects and their partners were not planning to have a child from screening to the end of the trial and agreed to use effective non-drug contraception during the trial. 5. ECOG score 0\~1, ASA grade I\~II 6. Subjects failed to respond to adequate treatment with any of the conventional antibiotics, immunomodulatory drugs (including steroids), anti-tumor necrosis factor-α (TNF-α) monoclonal antibodies and other biological agents. Exclusion Criteria: 1. Subjects with active infection evaluated by the investigator. 2. Subjects with Crohn\&amp;amp;amp;#39;s disease requiring immediate therapy. 3. Subjects with abscess or collections \&amp;amp;amp;gt;2 cm. 4. Subjects with rectal and/or anal stenosis and/or active proctitis. 5. Subjects who treated with systemic steroids in the 4 weeks prior to stem cells administration. 6. Subjects with abnormal laboratory results: liver function: total bilirubin \&amp;amp;amp;gt;=1.5 × ULN, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \&amp;amp;amp;gt;=2 × ULN; renal function: creatinine clearance below 60 mL/minute calculated using Cockcroft-Gault formula or by serum creatinine \&amp;amp;amp;gt;=1.5 × upper limit of normal (ULN). 7. Subjects with malignant tumors or a history of malignant tumors. 8. Subjects with severe, progressive, uncontrolled hepatic, hematological, gastrointestinal (except Crohn\&amp;amp;amp;#39;s disease), endocrine, pulmonary, cardiac, neurological, psychiatric, or cerebral diseases. 9. Serum virology test (HBeAg, HCV antibody, HIV antibody, Treponema pallidum antibody) positive. 10. Subjects allergic to Human serum albumin, human platelet lysate, gentamicin sulfate, anesthetic drug 11. Subjects who has received stem cells therapy. 12. Subjects who has major surgery or severe trauma within 6 months prior to the screening period. 13. Subjects who has received any investigational drug within 3 months prior to the screening. 14. Subjects deemed inappropriate by the investigator to participate in this clinical trial. 15. The female participant who is pregnant, or is lactating. 16. Not suitable for PET/CT examination. 17. Participants considered inappropriate to participate in this clinical trial **Maximum Age:** 70 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** E-mail:[email protected] **Name:** Miu Li Yan The First Affiliated Hospital of Soochow University **Phone:** 86+0512-67972858 **Role:** CONTACT ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ## Derived Section ### Condition Browse Module - Ancestors - ID: D000015212 - Term: Inflammatory Bowel Diseases - ID: D000005759 - Term: Gastroenteritis - ID: D000005767 - Term: Gastrointestinal Diseases - ID: D000004066 - Term: Digestive System Diseases - ID: D000007410 - Term: Intestinal Diseases - ID: D000020763 - Term: Pathological Conditions, Anatomical - ID: D000007412 - Term: Intestinal Fistula - ID: D000016154 - Term: Digestive System Fistula - ID: D000012002 - Term: Rectal Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M6638 - Name: Crohn Disease - Relevance: HIGH - As Found: Crohn's Disease - ID: M8532 - Name: Fistula - Relevance: HIGH - As Found: Fistula - ID: M14845 - Name: Rectal Fistula - Relevance: HIGH - As Found: Anal Fistula - ID: M10444 - Name: Intestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M17917 - Name: Inflammatory Bowel Diseases - Relevance: LOW - As Found: Unknown - ID: M8875 - Name: Gastroenteritis - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M22519 - Name: Pathological Conditions, Anatomical - Relevance: LOW - As Found: Unknown - ID: M10446 - Name: Intestinal Fistula - Relevance: LOW - As Found: Unknown - ID: M18616 - Name: Digestive System Fistula - Relevance: LOW - As Found: Unknown - ID: M14844 - Name: Rectal Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003424 - Term: Crohn Disease - ID: D000012003 - Term: Rectal Fistula - ID: D000005402 - Term: Fistula ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429228 **Brief Title:** Comparison of 1 Versus 2 Days Post-Operative Catheterization After Anterior Colporrhaphy **Official Title:** Comparison of 1 Versus 2 Days Post-Operative Catheterization After Anterior Colporrhaphy #### Organization Study ID Info **ID:** CAT_273219 #### Organization **Class:** OTHER **Full Name:** IRCCS San Raffaele ### Status Module #### Completion Date **Date:** 2024-09 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-09 **Type:** ESTIMATED #### Start Date **Date:** 2020-04-20 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Study First Submit Date:** 2024-01-24 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** IRCCS San Raffaele #### Responsible Party **Investigator Affiliation:** IRCCS San Raffaele **Investigator Full Name:** Stefano Salvatore **Investigator Title:** Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** Patients who undergo anterior vaginal wall plastic surgery and place the bladder catheter during surgery are selected. The purpose of the study is to evaluate the presence of statistically significant differences in bladder catheter repositioning within 12 hours after bladder catheter removal in the group of patients in whom the bladder catheter is removed on postoperative day I or II. Secondary outcomes include evaluation of the incidence of urinary tract infections, number of hospitalization days and total hospitalization costs for patients undergoing anterior vaginal wall surgery in patients in whom the bladder catheter is removed on postoperative day I or II. ### Conditions Module **Conditions:** - Catheter Related Complication - Anterior Vaginal Wall Prolapse ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 200 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Procedure: Catheter removal after surgery **Label:** Catheter removal in postoperative day I **Type:** EXPERIMENTAL #### Arm Group 2 **Intervention Names:** - Procedure: Catheter removal after surgery **Label:** Catheter removal in postoperative day II **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Catheter removal in postoperative day I - Catheter removal in postoperative day II **Description:** Removal of catheter placed during the procedure in first or second post-surgical days. **Name:** Catheter removal after surgery **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** After removal of the bladder catheter, on postoperative day I or II, the appearance of urinary urge will be assessed and, in case of spontaneous urination, the quantity of urine will be measured. In the event that after the waiting time of 6 hours an adequate urination stimulus does not arise, we will proceed with an ultrasound evaluation of bladder stagnation (RV) and the application of the department protocol, as follows: * if the sum of diuresis and RV is between 500 and 1000 cc, extemporaneous catheterization and re-evaluation after 4 hours are indicated * if the sum of diuresis and RV is \> 1000cc, positioning of a bladder catheter and maintenance of the same for 5-7 days with subsequent evaluation is indicated. **Measure:** differences in bladder catheter repositioning within 12 hours after bladder catheter removal **Time Frame:** 12 hours #### Secondary Outcomes **Description:** Before removing the catheter, a chemical-physical examination will be carried out; if this is positive, urine culture will be carried out. The diagnosis of urinary tract infection will be made with leukocyturia greater than 25 cells per field, positivity for urinary nitrite, presence of at least 20 bacteria per field, bacteriuria and/or more than 100,000 colony forming units associated with at least one of the following signs (fever, dysuria, increased urinary frequency, suprapubic pain, burning on urination or worsening of urinary incontinence). Patients with a positive culture and/or who show symptoms attributable to urinary tract infection will be subjected to antibiotic therapy. **Measure:** incidence of urinary tract infections for patients undergoing cystopexy surgery in patients in whom the bladder catheter is removed on postoperative day I or II. **Time Frame:** During hospital stay ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Women 18 years of age or older * Patients who are candidates for cystopexy surgery * Patients who have consented to the signing of the Informed Consent Exclusion Criteria: * Micturition dysfunction with preoperative bladder stagnation \> 200 cc at pessary evaluation * History of recurrent cystitis * Positive preoperative urine culture * Azotemia \> 40 mg/dL or creatininemia \> 1 mg/dL * Not collected signed consent endorsed * Diabetes mellitus * Contraindications to transurethral bladder catheterization * Major protocol violations due to unforeseen intraoperative complications (bladder and/or rectal damage, severe bleeding with need for urinary monitoring) **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Stefano Salvatore **Phone:** 0226434930 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Vittoria Benini **Role:** CONTACT #### Locations **Location 1:** **City:** Milan **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Stefano Salvatore - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Vittoria Benini - **Role:** CONTACT **Country:** Italy **Facility:** IRCCS San Raffaele Hospital **Status:** RECRUITING **Zip:** 20132 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020763 - Term: Pathological Conditions, Anatomical ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M14261 - Name: Prolapse - Relevance: HIGH - As Found: Prolapse - ID: M22519 - Name: Pathological Conditions, Anatomical - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000011391 - Term: Prolapse ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429215 **Acronym:** SCD-ReCODED **Brief Title:** REducing the Risk of COgnitive DEcline ad Dementia in Patients With Subjective Cognitive Decline Through an Immersive Virtual Reality and Telemedicine-based Multi-component Intervention: the SCD-ReCODED Study **Official Title:** Preventing Cognitive Decline and Dementia Through an Innovative Immersive Virtual Reality and Telemedicine-based Multi-component Intervention: a Randomized Controlled Trial #### Organization Study ID Info **ID:** PRIN 2022 PNRR P2022E3CZY #### Organization **Class:** OTHER **Full Name:** I.R.C.C.S. Fondazione Santa Lucia ### Status Module #### Completion Date **Date:** 2025-12 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2025-01 **Type:** ESTIMATED #### Start Date **Date:** 2024-06 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Study First Submit Date:** 2024-05-10 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** I.R.C.C.S. Fondazione Santa Lucia #### Responsible Party **Investigator Affiliation:** I.R.C.C.S. Fondazione Santa Lucia **Investigator Full Name:** Maria Stefania De Simone **Investigator Title:** Principal investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** Older adults with subjective cognitive decline (SCD) are at high risk of developing dementia and frequently experience subclinical symptoms (e.g., anxiety, depression) which are themselves associated with dementia and cognitive decline risk. To date, the lack of effective disease-modifying treatments, along with the reliable identification of modifiable lifestyle risk factors (e.g., cognitive activity, dietary habits, physical exercise), have led to growing interest to invest in non-pharmacological interventions that may reduce the prevalence and incidence of dementia and cognitive decline in older adults. In this framework, the aim of this project is to evaluate the efficacy of an Immersive Virtual Reality (IVR) and telemedicine-based multi-component intervention, combining cognitive training and a health and lifestyle education program, for preventing cognitive decline and dementia in at-risk individuals (i.e., SCD). For this purpose, a randomized, double-blinded controlled trial (RCT) will be conducted on seventy-five eligible individuals with SCD, who will be randomly assigned to one of three conditions: (a) multi-component intervention (MC-I), including SCD-tailored cognitive IVR training plus a health and lifestyle education program, (b) cognitive-only intervention (CO-I), including the SCD-tailored cognitive IVR training plus an active control for the education program, and (c) active control intervention (AC-I) for both cognitive training and education program. Intervention will be provided in 20 at-home sessions (4 sessions/week, each lasting about 30 minutes) over a period of 5 weeks. Outcome measures include clinical, neuropsychological, behavioural and neuroimaging data that will be collected before and immediately after intervention in order to detect potentially intervention-induced changes in objective cognitive functioning (primary outcome), subjective cognitive functioning, mood, quality of life and brain connectivity (secondary outcome). Users' compliance with IVR and telemedicine approach will be also evaluated, as well as individuals' factors affecting training efficacy. ### Conditions Module **Conditions:** - Subjective Cognitive Decline **Keywords:** - Subjective cognitive decline - Multi-component training - Non-pharmacological intervention - Virtual reality - Telemedicine ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - OUTCOMES_ASSESSOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 75 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** VR cognitive training + Psychoeducation program **Intervention Names:** - Device: Multi-component Intervention (MC-I): VR Cognitive training and Psychoeducation on health and lifestyle **Label:** Multi-component Intervention (MC-I) **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** VR Cognitive training + Psychoeducation active control **Intervention Names:** - Device: Cognitive-only intervention (CO-I): VR Cognitive training (+ Psychoeducation active control) **Label:** Cognitive-only intervention (CO-I) **Type:** ACTIVE_COMPARATOR #### Arm Group 3 **Description:** VR Cognitive active control + Psychoeducation active control **Intervention Names:** - Device: Active control intervention (AC-I): VR Cognitive active control + Psychoeducation active control **Label:** Active control intervention (AC-I) **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Multi-component Intervention (MC-I) **Description:** In a period of 5 consecutive weeks, participants will receive: * an interactive immersive virtual reality cognitive training for 30 minutes, 3 days per week. It consists in different tasks implemented in virtual real-like scenarios of daily living situations that target the following cognitive processes: long-term associative memory, relational binding, spatial pattern separation and pattern completion; * an interactive immersive virtual reality health and lifestyle education program for 30 minutes, 1 day per week. It consists in 360° videos aimed at advancing awareness and knowledge of the various health conditions associated with an increased risk of cognitive decline and dementia and helping participants to develop a healthier lifestyle. **Name:** Multi-component Intervention (MC-I): VR Cognitive training and Psychoeducation on health and lifestyle **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - Cognitive-only intervention (CO-I) **Description:** In a period of 5 consecutive weeks, participants will receive: * the interactive immersive virtual reality cognitive training as described in the MC-I condition, for about 30 minutes, 3 days per week; * an active control of the immersive virtual reality psychoeducation program for 30 minutes, 1 day per week. **Name:** Cognitive-only intervention (CO-I): VR Cognitive training (+ Psychoeducation active control) **Type:** DEVICE #### Intervention 3 **Arm Group Labels:** - Active control intervention (AC-I) **Description:** In a period of 5 consecutive weeks, participants will receive: * an active control of the immersive virtual reality cognitive training (participants will be requested to virtually carry out daily actions, in the same setting as those performed in cognitive immersive VR training, but they will follow prearranged instructions requiring very low cognitive demands) for about 30 minutes, 3 days per week; * an active control of the immersive virtual reality psychoeducation program for about 30 minutes, 1 day per week. **Name:** Active control intervention (AC-I): VR Cognitive active control + Psychoeducation active control **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** The Face-Name Associative Memory Exam (short form - FNAME12) is an associative long-term memory task that requires the participant to learn and retrieve 12 novel face-name and face-occupation pairs. It consists of two learning phases, followed by an immediate cued recall and a 30-min delayed recall and recognition trial. **Measure:** Cognitive functioning (1): change scores on the Face-Name Associative Memory Exam **Time Frame:** Baseline, post-intervention (around 6 weeks after baseline) **Description:** The Visual Short-Term Memory Binding Test is a recognition task based on a change detection paradigm for arrays of stimuli presented on a computer screen. Two conditions are investigated, that is, a shape-only condition as the first and a shape-color condition as the second. In both conditions, participants are asked to remember visual arrays of two or three black polygons (in the shape-only condition) or colored polygons (in the shape-color condition) presented for 2 s (study phase). **Measure:** Cognitive functioning (2): change scores on the Visual Short-Term Memory Binding Test **Time Frame:** Baseline, post-intervention (around 6 weeks after baseline) **Description:** The Spatial pattern separation test assesses the ability to differentiate partially overlapping patterns of activation in order to retrieve one pattern as separate from others that are similar. Specifically, it consists of 36 trials, in which the participant is required to learn the location of a grey circle on a sceen; then the participant is required to recognize the position of the previously-learned grey circle with respect to a foil located either to the left or the right of the target. **Measure:** Cognitive functioning (3): change scores on the Spatial pattern separation test **Time Frame:** Baseline, post-intervention (around 6 weeks after baseline) #### Secondary Outcomes **Description:** The Subjective Memory Complaints Questionnaire assesses the subjective experience of memory decline. It consists of two sections. Part I provides a global evaluation of memory concerns responses to four general questions (4 items); Part II provides an evaluation of memory concerns in daily life (27 items). For each of the 31 items, participants are asked to respond on a 4-point Likert scale (1 = No, it does not happen to me; 2 = Sometimes, but it does not worry me; 3 = Yes and it worries me; 4 = Yes and it constitutes a problemin at least one area ofmy life, e.g., work, family, leisure, relationships). Higher scores are indicative of more serious memory complaints. **Measure:** Transfer effect on self-perceived cognitive functioning: change scores on the Subjective Memory Complaints Questionnaire **Time Frame:** Baseline, post-intervention (around 6 weeks after baseline) **Description:** Connectomics changes after intervention will be investigated between pairs of regions of the whole brain (with particular interest in areas mainly involved in training-related cognitive processes) and in the global and local topological properties of large-scale networks through graph theoretical approach. **Measure:** Intervention-induced changes in whole-brain functional connectivity **Time Frame:** Baseline, post-intervention (around 6 weeks after baseline) **Measure:** Transfer effect on mood (1): change scores on the 30-item Geriatric Depression Scale **Time Frame:** Baseline, post-intervention (around 6 weeks after baseline) **Measure:** Transfer effect on mood (2): change scores on the State-Trait Anxiety Inventory **Time Frame:** Baseline, post-intervention (around 6 weeks after baseline) **Measure:** Transfer effect on mood (3): change scores on the 18-item Apathy Evaluation Scale **Time Frame:** Baseline, post-intervention (around 6 weeks after baseline) **Measure:** Transfer effect on quality of life and health status: Change scores on the Short Form-36 Health Survey **Time Frame:** Baseline, post-intervention (around 6 weeks after baseline) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Self-perceived decline in cognition compared to five years ago * Lack of objective cognitive impairment. Exclusion Criteria: * Clinically significant depression and anxiety; * Psychiatric disorders; * Unstable medical conditions. * Severe visual, auditory, verbal or physical impairments interfere with communication, command compliance, and strategy execution * Dizziness or epilepsy history; **Healthy Volunteers:** True **Maximum Age:** 80 Years **Minimum Age:** 55 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000019965 - Term: Neurocognitive Disorders - ID: D000001523 - Term: Mental Disorders - ID: D000003072 - Term: Cognition Disorders ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M6904 - Name: Dementia - Relevance: HIGH - As Found: Dementia - ID: M29705 - Name: Cognitive Dysfunction - Relevance: HIGH - As Found: Cognitive Decline - ID: M5204 - Name: Brain Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M21836 - Name: Neurocognitive Disorders - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown - ID: M6301 - Name: Cognition Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003704 - Term: Dementia - ID: D000060825 - Term: Cognitive Dysfunction ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429202 **Brief Title:** The Relationship Between Body Perception and Self-Esteem Level and Quality of Life in Adolescent Idiopathic Scoliosis **Official Title:** Examination of the Relationship Between Body Perception and Self-Esteem Level and Quality of Life in Adolescent Idiopathic Scoliosis #### Organization Study ID Info **ID:** Acetinkaya003 #### Organization **Class:** OTHER **Full Name:** Halic University ### Status Module #### Completion Date **Date:** 2024-06-10 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2024-05-30 **Type:** ESTIMATED #### Start Date **Date:** 2024-05-15 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Study First Submit Date:** 2024-05-14 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Halic University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Scoliosis is a three-dimensional, multifactorial disease that becomes more prevalent in adolescents, disrupts the three-dimensional mechanism and posture of the vertebra, causes deterioration in the person's body perception and cosmetic perception, and also causes negative effects on social life and quality of life. Although idiopathic scoliosis is more common during adolescence, its cause is not yet known. It is divided into three subheadings according to the age of onset. These are respectively; It is classified as Juvenile Idiopathic Scoliosis (0-3 years), Infantile Idiopathic Scoliosis (4-10 years), Adolescent Idiopathic Scoliosis (10 years and above). The most common one is Adolescent Idiopathic Scoliosis. Its incidence in girls is 4 times higher than in boys. This study aimed to examine the effects of body image and self-esteem on quality of life in idiopathic adolescent scoliosis patients and to determine whether there is a difference between genders. Additionally, it will be examined what effect the duration of corset use has on these parameters. **Detailed Description:** Scoliosis is a three-dimensional, multifactorial disease that becomes more prevalent in adolescents, disrupts the three-dimensional mechanism and posture of the vertebra, causes deterioration in the person's body perception and cosmetic perception, and also causes negative effects on social life and quality of life. Although idiopathic scoliosis is more common during adolescence, its cause is not yet known. It is divided into three subheadings according to the age of onset. These are respectively; It is classified as Juvenile Idiopathic Scoliosis (0-3 years), Infantile Idiopathic Scoliosis (4-10 years), Adolescent Idiopathic Scoliosis (10 years and above). The most common one is Adolescent Idiopathic Scoliosis. Its incidence in girls is 4 times higher than in boys. This study aimed to examine the effects of body image and self-esteem on quality of life in idiopathic adolescent scoliosis patients and to determine whether there is a difference between genders. Additionally, it will be examined what effect the duration of corset use has on these parameters. Thirty idiopathic adolescent scoliosis patients, boys and girls aged between 10 and 18, will be included in the study. Coopersmith Self-Esteem Inventory (CSEI) to evaluate body image, Walter Reed Visual Assessment Scale to evaluate body image, Scoliosis Research Society-22 Quality of Life Questionnaire to evaluate the level of quality of life, sociodemographic data form to obtain personal data, Statistical Package to analyze the data. for Social Science (SPSS) planned to use Windows version 22.0 ### Conditions Module **Conditions:** - Scoliosis; Adolescence - Self Esteem - Quality of Life **Keywords:** - idiopathic scoliosis - self esteem - body perception ### Design Module #### Design Info **Observational Model:** OTHER **Time Perspective:** CROSS_SECTIONAL #### Enrollment Info **Count:** 30 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Outcomes Module #### Primary Outcomes **Description:** Walter Reed Visual Assessment Scale (WRGDS) is an evaluation scale created from visual figures. It was developed by Pineda et al. in 2006, for use in individuals with scoliosis, to measure how a person thinks about the deformity in their own body and how severe it is perceived. **Measure:** Walter Reed Visual Assessment Scale **Time Frame:** at baseline **Description:** It is a self-assessment scale developed by Stanley Coopersmith in 1967. This test aims to measure the individual's thoughts about himself and his general sense of self-esteem. The form consists of 58 questions and includes 50 self-esteem items and 8 lie items. **Measure:** Coopersmith Self-Esteem Inventory (CSEI) **Time Frame:** at baseline **Description:** Scoliosis Research Society-22 is a 22-question quality of life scale specific to scoliosis. Developed by the Scoliosis Research Society, it has been translated into different languages and shown to be valid and reliable. **Measure:** Scoliosis Research Society-22 Quality of Life Questionnaire **Time Frame:** at baseline ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Volunteering to participate in the study and obtaining parental consent * Being between the ages of 10-18 * Being diagnosed with idiopathic scoliosis * Using a scoliosis brace for at least 3 months * Being within the normal range in body mass index Exclusion Criteria: * Having previously undergone spine surgery, having any mental problems, having non-idiopathic scoliosis and orthopedic disease. * Having a curve of less than 25 degrees **Maximum Age:** 18 Years **Minimum Age:** 10 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD - ADULT **Study Population:** 30 individuals between the ages of 10-18 diagnosed with Adolescent Idiopathic Scoliosis. As a general recommendation, Cohen states that if the d value is less than 0.2, the effect size can be defined as weak, if it is 0.5, it can be defined as medium, and if it is greater than 0.8, it can be defined as strong (Cohen, 1988). The minimum number of samples was calculated with the G\*Power 3.1.9 program. Accordingly, the minimum number of samples to be included in the study for an effect size of 0.5, statistical power of 80% and margin of error of 0.05 was calculated as 29. ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Ayşenur Çetinkaya **Phone:** +905077218827 **Role:** CONTACT #### Locations **Location 1:** **City:** Istanbul **Country:** Turkey **Facility:** Halic University **State:** Eyupsultan **Zip:** 2022 #### Overall Officials **Official 1:** **Affiliation:** Halic University **Name:** Ayşenur Çetinkaya **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000013121 - Term: Spinal Curvatures - ID: D000013122 - Term: Spinal Diseases - ID: D000001847 - Term: Bone Diseases - ID: D000009140 - Term: Musculoskeletal Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: All - Name: All Conditions - Abbrev: BXM - Name: Behaviors and Mental Disorders ### Condition Browse Module - Browse Leaves - ID: M15417 - Name: Scoliosis - Relevance: HIGH - As Found: Scoliosis - ID: M15918 - Name: Spinal Curvatures - Relevance: LOW - As Found: Unknown - ID: M15919 - Name: Spinal Diseases - Relevance: LOW - As Found: Unknown - ID: M5126 - Name: Bone Diseases - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: T6034 - Name: Quality of Life - Relevance: HIGH - As Found: Quality of Life ### Condition Browse Module - Meshes - ID: D000012600 - Term: Scoliosis ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429189 **Brief Title:** Home-Combo: an Online Home-based Combined Exercise Intervention for Women With Breast Cancer **Official Title:** An Online Home-based Combined Exercise Intervention With Self-selected Intensity for Women With Breast Cancer: The Home-Combo Randomized Controlled Trial. #### Organization Study ID Info **ID:** Home-Combo #### Organization **Class:** OTHER **Full Name:** Grupo Lusófona ### Status Module #### Completion Date **Date:** 2025-10-10 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2024-11-20 **Type:** ESTIMATED #### Start Date **Date:** 2024-11-10 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Study First Submit Date:** 2024-05-03 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Universidade Lusófona de Humanidades e Tecnologias **Class:** UNKNOWN **Name:** Grupo HPA **Class:** UNKNOWN **Name:** Associação Oncológica do Algarve **Class:** UNKNOWN **Name:** Liga Portuguesa Contra o Cancro **Class:** OTHER **Name:** Centro Hospitalar Universitario do Algarve #### Lead Sponsor **Class:** OTHER **Name:** Grupo Lusófona #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Background. Chemotherapy drugs carry many side effects that may hinder the functional performance of women with breast cancer (BC). Chemoresistance can lead to treatment failure. A relative dose intensity of chemotherapy \<85% is associated with a worse diagnosis and lower treatment efficacy. Exercise may modulate treatment response through its effects on the tumor microenvironment and treatment tolerability. The need for a pleasant and sustainable exercise practice is important, considering the psychological and physiological stress that accompanies women with a BC diagnosis during treatment. Studies investigating the effects of exercise interventions on chemotherapy completion rates are needed. Purpose. This study aims to investigate the effects of a self-selected intensity structured supervised home-based combined exercise intervention on the chemotherapy completion rates of women with BC. Secondly, the investigators intend to analyze the impact of this intervention on functional performance, quality of life, body composition, and physical activity levels. A 3-month follow-up will investigate if physically active behavior is sustained post-intervention. Methods. A 2-arm randomized controlled trial will be implemented in a real-world exercise setting to compare an online structured and supervised group aerobic and strength exercise intervention with an active control group during chemotherapy treatments. The study recruitment goal is 98 women with a BC diagnosis stage I-III who are scheduled to have neoadjuvant or adjuvant chemotherapy. Outcome measures will be obtained at baseline, mid-treatment (≈3 months), post-intervention (≈6 months), and 3-month follow-up. A mediation analysis will also be conducted. Hypothesis 1: Women in the intervention will have a better completion rate than those in the control group. Hypothesis 2: Women in the intervention will present better functional performance, body composition, PA levels, and quality of life than the control group. Hypothesis 3: In the post-intervention period, women in the intervention group will maintain a more physically active lifestyle than women in the control group. **Detailed Description:** Study setting The Home-Combo study will take place in the Algarve, and the sample will be recruited by medical referral from various public and private hospitals across the region. The intervention design will consider the PA/exercise preferences, perceived barriers, and facilitators of women with BC. This information will be collected before the intervention through a mixed-methods qualitative study that will include a survey and focus groups. The intervention will be conducted online to ensure the participants' safety during the chemotherapy treatment phase, as they may have compromised immunity. Also, this option was made to attenuate participants' burden caused by commuting requirements. Participants will be enrolled in two cohorts. Criteria for discontinuing or modifying allocated interventions Participants will be informed in the pre-study initial meeting that they may leave the study anytime. Participants will be asked to refrain from continuing the intervention if a worsening clinical condition prevents them from exercising and performing the assessments safely. The exercise program might be reviewed and tailored to the participants' condition across the intervention. Strategies to improve adherence Before implementing this study, a survey and focus-group-based study will be performed to adjust the exercise program to the preferences, perceived barriers, and facilitators of women with a breast cancer diagnosis, considering the environmental and cultural context from where the intervention will be conducted. The supervising professional will monitor adherence to the supervised sessions through presence registration. This study will also consider the participants' adherence to the control group. To attempt dropout minimization, the investigators will have an active control group. Concomitant care Physiotherapy treatments prescribed by the participant's primary physician and any exercises prescribed to be performed at home prescribed by the physiotherapist will be allowed during the intervention. Participants in the study will be asked not to engage in other exercise and PA programs or activities outside the program. Participants in the control group will not be prohibited from performing physical activities like brisk walking. Sample size Considering this study design, sample size calculations were made for the primary outcome with a factorial variance analysis with repeated measures as reference statistical analysis, giving an initial estimation of 82 participants. Based on previous findings and considering a 20% dropout, the sample size was estimated at 98 participants with a moderate effect size (a=0.05; statistical power=0.80) according to Cohen's D calculations, using G\* Power 3.1. Recruitment Recruitment will occur through medical referrals from primary physicians of several public and private hospitals in the Algarve region. Additionally, the project will be presented at breast cancer-themed congresses and events, and digital flyers with information about the study will be made to assist in disseminating the project and the recruitment process. A research team member will then contact patients referred by the doctors to receive detailed information about the study. Optionally, patients can call the research team directly or contact them through email if they prefer. After confirming eligibility criteria and interest in participating in the study, patients will be asked to attend an initial session where more information will be given, and the informed consent will be signed. During that session, participants will be told they are not obliged to participate in the study and may decide to leave the project. Consent for data collection or sharing will also be obtained. Data collection methods Assessments will be conducted in standardized conditions, in a clinical setting, in a calm and comfortable environment, in small groups, and performed by a qualified exercise professional. The assessments will be conducted in the morning, starting with the body composition measurements, followed by a 15-minute pause so participants can eat (since they will be weighted while fasting), preceded by a 10-minute warm-up with general movements to mobilize big muscle groups and the physical tests, that will be performed in the following order: shoulder angular measurements, strength, mobility, and aerobic endurance. Participants will be divided into small groups to facilitate instruction and conduction of the tests. Participants will receive the accelerometers one week before the field tests and return them on the physical assessment day. After the field measurements, all questionnaires will be delivered and answered through email (Google Forms) Plans to promote retention The conducting exercise professional will control participants' adherence to the exercise program through a presence registry collected by the research team member with access to the list of participants' numbers. After the session, the non-interventionist research team member will pass the presence list to the respective numbers of the participants for program adherence analysis. If a participant fails to attend a session, contact will be made to ensure the participant's welfare and motivate them to participate in the next session. The data analysis will not consider participants who fail to attend 50% or more sessions. Positive feedback will be given to the participants during the sessions, as positive feedback enhances feelings of competence, enjoyment, and interest in the activity 86. Additionally, participants will be encouraged to keep an activity diary where they may register all activities performed autonomously. Participants will be contacted one week before the assessment to confirm their availability and presence. Data from participants who fail to perform the assessments during the intervention period will be excluded from data analysis. After the intervention, participants will be contacted monthly to check their well-being and keep their interest and motivation in engaging in the follow-up assessment. Data management All the data collected in this study will be kept confidential, computerized, and encrypted in a database without any elements that may allow identification of the participants. After the participants have expressed interest and written informed consent, a number corresponding to the participant ID during the study will be provided. When the participant receives her ID number, all data inserted in the databases will not be directly linked to the participant's personal identification. A dataset will be created for each assessment time point. All datasets will be maintained by the members responsible for the investigation on a secure server of CIDEFES-UL for ten years and will be used exclusively for research purposes. Datasets used for specific analyses or to develop sub-studies will contain only the necessary variables and the demographical indicators provided to the research team members upon request to the leading investigator. Statistical methods All data will be analyzed using IBM SPSS (version 29.0). Factorial ANCOVAS with repeated measures will be used for the primary and secondary outcomes, adjusted for potential covariates (e.g., concomitant treatments, BC diagnosis, neo-adjuvant/ adjuvant chemotherapy). Independent sample T-tests will be used to compare results between groups at each time point, considering chemotherapy completers versus non-completers. A Fisher's exact test will compare the proportion of participants who needed chemotherapy adjustments from those who did not. The intention-to-treat analysis will be conducted to ensure that all participants are included in the overall assessment, considering their compliance with the study protocol. The Last Observation Carried Forward method will be used to input missing data values. A per-protocol analysis will also be conducted without participants who failed to complete at least 50% of the training sessions. Normality plots and Kolmogorov-Smirnov tests will be performed to test the normality of outcome variables. If normality is not satisfied, non-parametric tests will be applied (e.g., Krustal-Wallis). Mediators of change (i.e., mechanisms by which RDI) will be explored using structural equation modeling (AMOS 18.0) and multiple mediation analysis (PROCESS macro for SPSS). Putative candidates will include treatment (e.g., dose planned vs. given dose, planned cycles minimum/maximum, treatment interruption ratios, response to treatment, percentage of participants who needed dose adjustments, and the mean value of dose adjustment), and physiological (e.g., body composition, functional performance, handgrip strength, PA levels) variables. Mediation occurs when a causal effect of an independent variable occurs on a dependent variable, partly or entirely explained by a mediator. Indirect effects testing will be performed using Preacher and Hayes' procedures. Data monitoring A data monitoring committee will not be required for this trial as the interventions pose minimal risk, and participants will be protected by personal insurance throughout the study. Harms All participants will have their adverse events monitored throughout the study, whether directly related to the intervention or not (if applicable). This monitoring will be done through self-reporting at the start of each session, registered for analysis and report purposes, or by their primary care physicians. Participants will be advised to contact the clinical team if they have difficulties. Auditing Two authors will supervise all trial procedures and cross-check the interventionist actions and study processes. Additionally, an independent person external to the project will review the protocol. Research ethics approval This study has received ethical approval from the collaborating hospital (UAIF 069/2024). This trial will follow the World Medical Association's Declaration of Helsinki for Human Studies. Consent or assent Healthcare professionals will approach potential participants to determine if they are interested in participating. If they express interest, they will be referred to a research team member who will contact them. Additionally, interested participants will be allowed to share the study information with other women who have been diagnosed with breast cancer. If any of these women express interest in participating, they will also be considered after obtaining medical clearance. Once the eligibility criteria for the study are confirmed and the women express their interest in participating, they will receive the Informed Consent through email. In the informational session, women will be asked to digitally fill out and sign the Informed Consent. It will be clear to the participants that they can withdraw their consent anytime. After the informational session, a PDF copy of the signed Informed Consent will be emailed to each participant. The research team will also take additional measures to collect and share the participants' data. ### Conditions Module **Conditions:** - Breast Cancer - Chemotherapy Effect **Keywords:** - Breast cancer - Home-based exercise - Functional performance - Body composition - Physical activity - Quality of life ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** 2-arm pragmatic and superiority randomized controlled trial with an intervention and an active control group, with a 1:1 allocation ratio. Participants in this group will perform a home-based combined exercise program throughout their chemotherapy treatments, starting within 1-2 weeks of its start and ending within 3-4 weeks post-treatment completion. Women randomized to the control group will receive weekly 30-minute supervised sessions with breathing, stretching, relaxation exercises, and meditation during the intervention period. ##### Masking Info **Masking:** TRIPLE **Masking Description:** Participants will be told they are part of an exercise intervention without any mention of a control group. Healthcare professionals responsible for the chemotherapy prescription and administration and registering all clinical information will be blinded to the participants' groups. None of the research team members will know the number of participants, so data analysis will be performed in a blinded setting. If, at any given moment, a participant reveals her number to a research team member, all posterior data from that participant will be disregarded. If a participant decides to leave the study or must abandon it due to health complications, the team member with the number information will be informed, and data will be disregarded from the analysis. **Who Masked:** - PARTICIPANT - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 98 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Exercise intervention will be led by qualified exercise professionals online via Zoom. It will consist of two weekly 60-minute online exercise group sessions: a 5-minute warm-up, 30-minute resistance training, and a 20-minute aerobic exercise component, finishing with a 5-minute cooldown. The warm-up will consist of mobility and activation movements. The resistance training component will consist of 9 exercises involving large muscle groups, performed with body weight or free weights. The exercises will be completed in 2-3 sets of 10-15 repetitions. The aerobic component will consist of low-impact dance exercises that move large muscle groups to increase heart rate. The cooldown will consist of breathing exercises and light stretches. **Intervention Names:** - Behavioral: Home-based combined exercise program with self-selected intensity **Label:** Home-based combined exercise **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** The control group will receive weekly 30-minute supervised sessions with breathing, stretching, relaxation exercises, and meditation. **Intervention Names:** - Behavioral: Home-based combined exercise program with self-selected intensity **Label:** Active control group **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Active control group - Home-based combined exercise **Description:** Before the beginning of the exercise program, participants will receive an education session on how to use Borg's Perceived Rate of Exertion Scale (RPE) to monitor their effort during aerobic and resistance training and tips on when they may increase the exercise intensity. During the training sessions, participants in the intervention group will be asked to choose their preferred load to execute each exercise in the resistance component, told to perform the aerobic exercises at their preferred speed, and informed that they can stop exercising whenever they need to rest. The exercise professional may suggest increasing loads in specific exercises, but these increases will not be imposed on the participants. Attendance to the sessions in the intervention and control groups will be registered. Additionally, women in this group will be encouraged to perform brisk walking at their preferred intensity and receive a pedometer to increase walking motivation. **Name:** Home-based combined exercise program with self-selected intensity **Other Names:** - Home-combo **Type:** BEHAVIORAL ### Outcomes Module #### Other Outcomes **Description:** Participants' demographic information (e.g., age, education, marital status, and economic status) will be collected through a general information questionnaire **Measure:** Demographics **Time Frame:** Assessments will be performed at two time points: baseline (throughout recruitment period completion, 1 year), post-intervention (6-12 months) **Description:** PA history will be collected through a general information questionnaire **Measure:** Physical activity history **Time Frame:** Assessments will be performed atbaseline (throughout recruitment period completion, 1 year) **Description:** Clinical history data will be retrieved from their medical records after they sign the informed consent form. **Measure:** Medical history **Time Frame:** Assessments will be performed at three time points: baseline (throughout recruitment period completion, 1 year ), mid-treatment (3-6 months), post-intervention (6-12 months) #### Primary Outcomes **Description:** The outcome will be reported as the mean RDI (mg.m-2/wk-1), which corresponds to a fraction of the planned chemotherapy dose intensity, by dividing the dose of chemotherapy per square meter (of surface area where the drug is related) in each cycle by the number of weeks in a cycle. Information regarding the planned chemotherapy treatment and the effectively received treatment (i.e., dose, type, and duration) will be acquired from medical records after signing the informed consent 53,19. Successful chemotherapy completion rate will be considered if the RDI is ≥85% of the planned treatment. Calculations to compare the actual chemotherapy dose intensity received and the initially planned dose intensity will be calculated as total milligrams of chemotherapy divided by the product of the body surface (in square meters) and total weeks of treatment. The RDI results from the actual dose intensity received are divided by the planned dose intensity. **Measure:** Chemotherapy completion rates **Time Frame:** Assessments will be performed at three time points: baseline (throughout recruitment period completion, 1 year ), mid-treatment (3-6 months), post-intervention (6-12 months). #### Secondary Outcomes **Description:** The 6-minute walk test will assess aerobic endurance, a standardized field test performed indoors in a 30-meter corridor with two turning points. Participants will be asked to walk the maximum distance possible. **Measure:** Functional performance **Time Frame:** Assessments will be performed at four time points: baseline (throughout recruitment period completion, 1 year ), mid-treatment (3-6 months), post-intervention (6-12 months), 3 month follow-up (throughout the study completion up to 2 years) **Description:** Arm curls will assess upperbody strength. Participants will be instructed to perform as many repetitions as possible for 30 seconds with a 5-pound dumbbell. **Measure:** Functional performance **Time Frame:** Assessments will be performed at four time points: baseline (throughout recruitment period completion, 1 year ), mid-treatment (3-6 months), post-intervention (6-12 months), 3 month follow-up (throughout the study completion up to 2 years) **Description:** Sit-to-stand tests assess lower body strength. Participants will be instructed to stand upright and sit entirely back on a chair as many times as possible within 30 seconds, maintaining their feet steady on the ground and the arms crossed with hands on the shoulders **Measure:** Functional performance **Time Frame:** Assessments will be performed at four time points: baseline (throughout recruitment period completion, 1 year ), mid-treatment (3-6 months), post-intervention (6-12 months), 3 month follow-up (throughout the study completion up to 2 years) **Description:** Handgrip strength will be measured using a dynamometer and considered to the nearest 0.1kg. While performing the handgrip test for each hand, participants will be instructed to stand upright with feet at hip width and elbows completely stretched while applying the maximum grip continuously for more than 3 seconds. **Measure:** Functional performance **Time Frame:** Assessments will be performed at four time points: baseline (throughout recruitment period completion, 1 year ), mid-treatment (3-6 months), post-intervention (6-12 months), 3 month follow-up (throughout the study completion up to 2 years) **Description:** Timed up-and-go tests will assess participants' overall mobility. Participants will be instructed to rise from a chair, walk 2.44 meters, turn around, walk back to the chair, and sit down. **Measure:** Functional performance **Time Frame:** Assessments will be performed at four time points: baseline (throughout recruitment period completion, 1 year ), mid-treatment (3-6 months), post-intervention (6-12 months), 3 month follow-up (throughout the study completion up to 2 years) **Description:** A goniometer will perform shoulder flexion and abduction angular measures on both sides. **Measure:** Functional performance **Time Frame:** Assessments will be performed at four time points: baseline (throughout recruitment period completion, 1 year ), mid-treatment (3-6 months), post-intervention (6-12 months), 3 month follow-up (throughout the study completion up to 2 years) **Description:** Upper limb flexibility will be assessed using the back scratch test. Participants will be instructed to pass one hand over the shoulder and the other from the bottom of the back, trying to reach both hands as close as possible. **Measure:** Functional performance **Time Frame:** Assessments will be performed at four time points: baseline (throughout recruitment period completion, 1 year ), mid-treatment (3-6 months), post-intervention (6-12 months), 3 month follow-up (throughout the study completion up to 2 years) **Description:** Body composition will be measured through bioelectrical impedance (Impedimed Australia). Data regarding weight, fat mass, lean mass, water percentage, bone mass, visceral fat, and phase angle will be collected from the scale. Participants will be asked to maintain their dietary patterns before the test and refrain from intense exercise the day before. The measurement will be performed under standardized conditions. The height measurement will be considered to the nearest 0.1 cm of the participants and will be performed using a balance-mounted stadiometer (SECA, Germany), with the participants standing and bare-footed. Body weight will be measured to the nearest 0.1kg with a digital scale. BMI (kg/m2) will be calculated from weight (kg) and height (m). Participants will be asked to maintain their dietary patterns before the test and refrain from intense exercise the day before. **Measure:** Body composition **Time Frame:** Assessments will be performed at four time points: baseline (throughout recruitment period completion, 1 year ), mid-treatment (3-6 months), post-intervention (6-12 months), 3 month follow-up (throughout the study completion up to 2 years) **Description:** The height measurement will be considered to the nearest 0.1 cm of the participants and will be performed using a balance-mounted stadiometer (SECA, Germany), with the participants standing barefoot. **Measure:** Body composition **Time Frame:** Assessments will be performed at four time points: baseline (throughout recruitment period completion, 1 year ), mid-treatment (3-6 months), post-intervention (6-12 months), 3 month follow-up (throughout the study completion up to 2 years) **Description:** Body weight will be measured with a digital scale to the nearest 0.1kg. **Measure:** Body composition **Time Frame:** Assessments will be performed at four time points: baseline (throughout recruitment period completion, 1 year ), mid-treatment (3-6 months), post-intervention (6-12 months), 3 month follow-up (throughout the study completion up to 2 years) **Description:** BMI (kg/m2) will be calculated from weight (kg) and height (m). **Measure:** Body composition **Time Frame:** Assessments will be performed at four time points: baseline (throughout recruitment period completion, 1 year ), mid-treatment (3-6 months), post-intervention (6-12 months), 3 month follow-up (throughout the study completion up to 2 years) **Description:** PA levels and SB will be assessed using accelerometry (GT9 link, Actigraph). Participants will be instructed to wear the device on an elastic belt on the non-dominant hip for seven days during all waking hours, removing only to sleep. The sampling units (epochs) will be settled to 1s to ease data analysis and ensure the appropriate sensitivity of the device during low-intensity activities. According to specific established thresholds, the accelerometer counts will be categorized into sedentary, light, moderate, and vigorous activity levels. Any interval of 60 or more minutes with continuous zero counts will be considered non-wear time. **Measure:** Physical Activity and Sedentary Behavior **Time Frame:** Assessments will be performed at four time points: baseline (throughout recruitment period completion, 1 year ), mid-treatment (3-6 months), post-intervention (6-12 months), 3 month follow-up (throughout the study completion up to 2 years) **Description:** The International Physical Activity Questionnaire Short-Form (IPAQ-SF) comprises nine items that measure the weekly time spent on all intensities PA (i.e., light, moderate, and vigorous) and time spent sitting on week and weekend days. Total PA scores are calculated from the collected data and discriminated by intensity. **Measure:** Physical Activity and Sedentary Behavior **Time Frame:** Assessments will be performed at four time points: baseline (throughout recruitment period completion, 1 year ), mid-treatment (3-6 months), post-intervention (6-12 months), 3 month follow-up (throughout the study completion up to 2 years) **Description:** Quality of life will be assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30).The EORT QLQ-C30 questionnaire consists of 30 items, grouped into 8 multi-item scales (i.e., functional: physical, role, emotional, cognitive, and social; symptom: fatigue, pain, and nausea), one global health status and quality of life subscale, and 6 single-item questions (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). **Measure:** General quality of life and breast-cancer specitfic quality of life **Time Frame:** Assessments will be performed at four time points: baseline (throughout recruitment period completion, 1 year ), mid-treatment (3-6 months), post-intervention (6-12 months), 3 month follow-up (throughout the study completion up to 2 years) **Description:** The specific module EORTC QLQ-BR45 will measure breast cancer-related quality of life. The breast cancer module QLQ-BR45 comprises five functional subscales (body image, future perspective, sexual functioning, sexual enjoyment, and breast satisfaction) and seven symptoms subscales (arm symptoms, breast symptoms, endocrine therapy, skin mucositis, endocrine sexual symptoms, systemic therapy side effects, and upset hair loss), for a total of 45 items. **Measure:** General quality of life and breast-cancer specitfic quality of life **Time Frame:** Assessments will be performed at four time points: baseline (throughout recruitment period completion, 1 year ), mid-treatment (3-6 months), post-intervention (6-12 months), 3 month follow-up (throughout the study completion up to 2 years) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Breast cancer stage I-III diagnosis * Scheduled to receive neoadjuvant or adjuvant chemotherapy * Have acess to a computer Exclusion Criteria: * Medical conterindication to perform exercise or physical assessments due to concomitant comorbidity * Non-controlled health conditions or diseases * Psychological illness * Currently enrolled in a structured exercise program * Unable to complete the entire program (e.g., due to scheduled surgery or personal commitments) * Pregnancy * Worsening of clinical condition during intervention **Gender Based:** True **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Pedro GF Ramos, Msc **Phone:** 928159936 **Phone Ext:** 351 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Pedro B. Júdice, PhD **Phone:** 217515500 **Phone Ext:** 351 **Role:** CONTACT #### Locations **Location 1:** **City:** Lisboa **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Pedro B. Júdice, PhD - **Phone:** 217515500 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Eliana V. Carraça, PhD - **Phone:** 217515500 - **Role:** CONTACT ***Contact 3:*** - **Name:** Pedro GF Ramos, Msc - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 4:*** - **Name:** Nuno Dias, Msc - **Role:** SUB_INVESTIGATOR **Country:** Portugal **Facility:** Universidade Lusófona, Centro de Lisboa **Zip:** 1749-024 #### Overall Officials **Official 1:** **Affiliation:** CIDEFES **Name:** Pedro B. Júdice, PhD **Role:** STUDY_DIRECTOR **Official 2:** **Affiliation:** CIDEFES **Name:** Eliana V. Carraça, PhD **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **Access Criteria:** The corresponding author will make anonymized trial data available for non-commercial research purposes upon reasonable request. **Description:** The corresponding author will make anonymized trial data available for non-commercial research purposes upon reasonable request. This trial's findings will be disseminated through publication in leading international oncology scientific journals and presentations at national and international conferences. In addition. the results and mediation analysis will be produced and published. As this is a pragmatic trial with highly applicable outcomes for participants and decision-makers, it presents potential for future widespread implementation through relevant stakeholders. **Info Types:** - STUDY_PROTOCOL **IPD Sharing:** YES **Time Frame:** Dissemination policy This trial's findings will be disseminated through publication in leading international oncology scientific journals and presentations at national and international conferences. In addition. the results and mediation analysis will be produced and published. As this is a pragmatic trial with highly applicable outcomes for participants and decision-makers, it presents potential for future widespread implementation through relevant stakeholders. ### References Module #### References **Citation:** Arnold M, Morgan E, Rumgay H, Mafra A, Singh D, Laversanne M, Vignat J, Gralow JR, Cardoso F, Siesling S, Soerjomataram I. Current and future burden of breast cancer: Global statistics for 2020 and 2040. Breast. 2022 Dec;66:15-23. doi: 10.1016/j.breast.2022.08.010. Epub 2022 Sep 2. **PMID:** 36084384 **Citation:** Giaquinto AN, Sung H, Miller KD, Kramer JL, Newman LA, Minihan A, Jemal A, Siegel RL. Breast Cancer Statistics, 2022. CA Cancer J Clin. 2022 Nov;72(6):524-541. doi: 10.3322/caac.21754. Epub 2022 Oct 3. **PMID:** 36190501 **Citation:** Leidy NK. Functional status and the forward progress of merry-go-rounds: toward a coherent analytical framework. Nurs Res. 1994 Jul-Aug;43(4):196-202. **PMID:** 8047422 **Citation:** Tong CKW, Lau B, Davis MK. Exercise Training for Cancer Survivors. Curr Treat Options Oncol. 2020 May 27;21(7):53. doi: 10.1007/s11864-020-00752-w. **PMID:** 32462229 **Citation:** Nygren P; SBU-group. Swedish Council on Technology Assessment in Health Care. What is cancer chemotherapy? Acta Oncol. 2001;40(2-3):166-74. doi: 10.1080/02841860151116204. **PMID:** 11441929 **Citation:** Kerr AJ, Dodwell D, McGale P, Holt F, Duane F, Mannu G, Darby SC, Taylor CW. Adjuvant and neoadjuvant breast cancer treatments: A systematic review of their effects on mortality. Cancer Treat Rev. 2022 Apr;105:102375. doi: 10.1016/j.ctrv.2022.102375. Epub 2022 Mar 4. **PMID:** 35367784 **Citation:** Alfarouk KO, Stock CM, Taylor S, Walsh M, Muddathir AK, Verduzco D, Bashir AH, Mohammed OY, Elhassan GO, Harguindey S, Reshkin SJ, Ibrahim ME, Rauch C. Resistance to cancer chemotherapy: failure in drug response from ADME to P-gp. Cancer Cell Int. 2015 Jul 15;15:71. doi: 10.1186/s12935-015-0221-1. eCollection 2015. **PMID:** 26180516 **Citation:** Engle K, Kumar G. Cancer multidrug-resistance reversal by ABCB1 inhibition: A recent update. Eur J Med Chem. 2022 Sep 5;239:114542. doi: 10.1016/j.ejmech.2022.114542. Epub 2022 Jun 17. **PMID:** 35751979 **Citation:** Longo DL, Duffey PL, DeVita VT Jr, Wesley MN, Hubbard SM, Young RC. The calculation of actual or received dose intensity: a comparison of published methods. J Clin Oncol. 1991 Nov;9(11):2042-51. doi: 10.1200/JCO.1991.9.11.2042. **PMID:** 1941063 **Citation:** Lyman GH, Dale DC, Crawford J. Incidence and predictors of low dose-intensity in adjuvant breast cancer chemotherapy: a nationwide study of community practices. J Clin Oncol. 2003 Dec 15;21(24):4524-31. doi: 10.1200/JCO.2003.05.002. **PMID:** 14673039 **Citation:** Wildiers H, Reiser M. Relative dose intensity of chemotherapy and its impact on outcomes in patients with early breast cancer or aggressive lymphoma. Crit Rev Oncol Hematol. 2011 Mar;77(3):221-40. doi: 10.1016/j.critrevonc.2010.02.002. Epub 2010 Mar 15. **PMID:** 20227889 **Citation:** Bland KA, Zadravec K, Landry T, Weller S, Meyers L, Campbell KL. Impact of exercise on chemotherapy completion rate: A systematic review of the evidence and recommendations for future exercise oncology research. Crit Rev Oncol Hematol. 2019 Apr;136:79-85. doi: 10.1016/j.critrevonc.2019.02.005. Epub 2019 Feb 16. **PMID:** 30878132 **Citation:** Ashcraft KA, Warner AB, Jones LW, Dewhirst MW. Exercise as Adjunct Therapy in Cancer. Semin Radiat Oncol. 2019 Jan;29(1):16-24. doi: 10.1016/j.semradonc.2018.10.001. **PMID:** 30573180 **Citation:** Wang Q, Zhou W. Roles and molecular mechanisms of physical exercise in cancer prevention and treatment. J Sport Health Sci. 2021 Mar;10(2):201-210. doi: 10.1016/j.jshs.2020.07.008. Epub 2020 Jul 30. **PMID:** 32738520 **Citation:** Zhu C, Ma H, He A, Li Y, He C, Xia Y. Exercise in cancer prevention and anticancer therapy: Efficacy, molecular mechanisms and clinical information. Cancer Lett. 2022 Sep 28;544:215814. doi: 10.1016/j.canlet.2022.215814. Epub 2022 Jul 5. **PMID:** 35803475 **Citation:** Kampshoff CS, Jansen F, van Mechelen W, May AM, Brug J, Chinapaw MJ, Buffart LM. Determinants of exercise adherence and maintenance among cancer survivors: a systematic review. Int J Behav Nutr Phys Act. 2014 Jul 2;11:80. doi: 10.1186/1479-5868-11-80. **PMID:** 24989069 **Citation:** Sheill G, Guinan E, Brady L, Hevey D, Hussey J. Exercise interventions for patients with advanced cancer: A systematic review of recruitment, attrition, and exercise adherence rates. Palliat Support Care. 2019 Dec;17(6):686-696. doi: 10.1017/S1478951519000312. **PMID:** 31109383 **Citation:** Ng AH, Ngo-Huang A, Vidal M, Reyes-Garcia A, Liu DD, Williams JL, Fu JB, Yadav R, Bruera E. Exercise Barriers and Adherence to Recommendations in Patients With Cancer. JCO Oncol Pract. 2021 Jul;17(7):e972-e981. doi: 10.1200/OP.20.00625. Epub 2021 Mar 19. **PMID:** 33739853 **Citation:** Mijwel S, Bolam KA, Gerrevall J, Foukakis T, Wengstrom Y, Rundqvist H. Effects of Exercise on Chemotherapy Completion and Hospitalization Rates: The OptiTrain Breast Cancer Trial. Oncologist. 2020 Jan;25(1):23-32. doi: 10.1634/theoncologist.2019-0262. Epub 2019 Aug 7. **PMID:** 31391297 **Citation:** Sanft T, Harrigan M, McGowan C, Cartmel B, Zupa M, Li FY, Ferrucci LM, Puklin L, Cao A, Nguyen TH, Neuhouser ML, Hershman DL, Basen-Engquist K, Jones BA, Knobf T, Chagpar AB, Silber A, Tanasijevic A, Ligibel JA, Irwin ML. Randomized Trial of Exercise and Nutrition on Chemotherapy Completion and Pathologic Complete Response in Women With Breast Cancer: The Lifestyle, Exercise, and Nutrition Early After Diagnosis Study. J Clin Oncol. 2023 Dec 1;41(34):5285-5295. doi: 10.1200/JCO.23.00871. Epub 2023 Sep 1. **PMID:** 37656930 **Citation:** Denton F, Power S, Waddell A, Birkett S, Duncan M, Harwood A, McGregor G, Rowley N, Broom D. Is It Really Home-Based? A Commentary on the Necessity for Accurate Definitions across Exercise and Physical Activity Programmes. Int J Environ Res Public Health. 2021 Sep 1;18(17):9244. doi: 10.3390/ijerph18179244. **PMID:** 34501833 **Citation:** Coughlin SS, Caplan LS, Williams V. Home-based physical activity interventions for breast cancer patients receiving primary therapy: a systematic review. Breast Cancer Res Treat. 2019 Dec;178(3):513-522. doi: 10.1007/s10549-019-05424-4. Epub 2019 Sep 6. **PMID:** 31493034 **Citation:** Bates-Fraser LC, Riley S, Stopforth C, Moertl K, Edgar K, Stoner L, Hanson ED. Home-based exercise improves quality of life in breast and prostate cancer survivors: A meta-analysis. PLoS One. 2023 Apr 20;18(4):e0284427. doi: 10.1371/journal.pone.0284427. eCollection 2023. **PMID:** 37079635 **Citation:** Ramos PGF, Judice PB, Nobre I, Carraca EV. Home-based exercise interventions' impact on breast cancer survivors' functional performance: a systematic review. J Cancer Surviv. 2024 Feb 15. doi: 10.1007/s11764-024-01545-y. Online ahead of print. **PMID:** 38356019 **Citation:** Dinapoli L, Colloca G, Di Capua B, Valentini V. Psychological Aspects to Consider in Breast Cancer Diagnosis and Treatment. Curr Oncol Rep. 2021 Mar 11;23(3):38. doi: 10.1007/s11912-021-01049-3. **PMID:** 33709235 **Citation:** El Kheir DYM, Ibrahim AHM. Epidemiological assessment of distress during chemotherapy: who is affected? J Taibah Univ Med Sci. 2019 Oct 8;14(5):448-453. doi: 10.1016/j.jtumed.2019.08.004. eCollection 2019 Oct. **PMID:** 31728143 **Citation:** Ekkekakis P. Let them roam free? Physiological and psychological evidence for the potential of self-selected exercise intensity in public health. Sports Med. 2009;39(10):857-88. doi: 10.2165/11315210-000000000-00000. **PMID:** 19757863 **Citation:** Schleicher E, McAuley E, Courneya KS, Anton P, Ehlers DK, Phillips SM, Brown NI, Oster RA, Pekmezi D, Rogers LQ. Breast cancer survivors' exercise preferences change during an exercise intervention are associated with post-intervention physical activity. J Cancer Surviv. 2023 Apr 29. doi: 10.1007/s11764-023-01389-y. Online ahead of print. **PMID:** 37120460 **Citation:** Chen X, Shi X, Yu Z, Ma X. High-intensity interval training in breast cancer patients: A systematic review and meta-analysis. Cancer Med. 2023 Sep;12(17):17692-17705. doi: 10.1002/cam4.6387. Epub 2023 Aug 17. **PMID:** 37587859 **Citation:** Ekkekakis P, Biddle SJH. Extraordinary claims in the literature on high-intensity interval training (HIIT): IV. Is HIIT associated with higher long-term exercise adherence? Psychol Sport Exerc. 2023 Jan;64:102295. doi: 10.1016/j.psychsport.2022.102295. Epub 2022 Sep 17. **PMID:** 37665824 **Citation:** Bolam KA, Mijwel S, Rundqvist H, Wengstrom Y. Two-year follow-up of the OptiTrain randomised controlled exercise trial. Breast Cancer Res Treat. 2019 Jun;175(3):637-648. doi: 10.1007/s10549-019-05204-0. Epub 2019 Mar 26. **PMID:** 30915663 **Citation:** Ramirez-Parada K, Courneya KS, Muniz S, Sanchez C, Fernandez-Verdejo R. Physical activity levels and preferences of patients with breast cancer receiving chemotherapy in Chile. Support Care Cancer. 2019 Aug;27(8):2941-2947. doi: 10.1007/s00520-018-4595-1. Epub 2018 Dec 18. **PMID:** 30564935 **Citation:** Alves RC, Enes A, Follador L, Prestes J, DA Silva SG. Effect of Different Training Programs at Self-Selected Intensity on Body Composition, Perceptual Responses and Fitness Outcomes in Obese Women. Int J Exerc Sci. 2022 Feb 1;15(4):373-385. eCollection 2022. **PMID:** 36895844 **Citation:** Glass SC, Ahmad S, Gabler T. Effectiveness of a 2-Week Strength Training Learning Intervention on Self-selected Weight-Training Intensity. J Strength Cond Res. 2020 Sep;34(9):2443-2448. doi: 10.1519/JSC.0000000000003729. **PMID:** 32732772 **Citation:** Ratamess NA, Faigenbaum AD, Hoffman JR, Kang J. Self-selected resistance training intensity in healthy women: the influence of a personal trainer. J Strength Cond Res. 2008 Jan;22(1):103-11. doi: 10.1519/JSC.0b013e31815f29cc. **PMID:** 18296962 **Citation:** Power, S., Rowley, N., Duncan, M. & Broom, D. Co-Designing and Refining a Home-Based Exercise Programme for Adults Living with Overweight and Obesity: Insight from People with Lived Experience. Obesities 3, 132-145 (2023). **Citation:** Gildea GC, Spence RR, Jones TL, Turner JC, Macdonald ER, Hayes SC, Sandler CX. Barriers, facilitators, perceptions and preferences influencing physical activity participation, and the similarities and differences between cancer types and treatment stages - A systematic rapid review. Prev Med Rep. 2023 May 24;34:102255. doi: 10.1016/j.pmedr.2023.102255. eCollection 2023 Aug. **PMID:** 37273528 **Citation:** Chan AW, Tetzlaff JM, Gotzsche PC, Altman DG, Mann H, Berlin JA, Dickersin K, Hrobjartsson A, Schulz KF, Parulekar WR, Krleza-Jeric K, Laupacis A, Moher D. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. 2013 Jan 8;346:e7586. doi: 10.1136/bmj.e7586. **PMID:** 23303884 **Citation:** Kraemer MB, Priolli DG, Reis IGM, Pelosi AC, Garbuio ALP, Messias LHD. Home-based, supervised, and mixed exercise intervention on functional capacity and quality of life of colorectal cancer patients: a meta-analysis. Sci Rep. 2022 Feb 15;12(1):2471. doi: 10.1038/s41598-022-06165-z. **PMID:** 35169171 **Citation:** Sharma A, Jasrotia S, Kumar A. Effects of Chemotherapy on the Immune System: Implications for Cancer Treatment and Patient Outcomes. Naunyn Schmiedebergs Arch Pharmacol. 2024 May;397(5):2551-2566. doi: 10.1007/s00210-023-02781-2. Epub 2023 Oct 31. **PMID:** 37906273 **Citation:** Courneya KS, Segal RJ, Vallerand JR, Forbes CC, Crawford JJ, Dolan LB, Friedenreich CM, Reid RD, Gelmon K, Mackey JR, McKenzie DC. Motivation for Different Types and Doses of Exercise During Breast Cancer Chemotherapy: a Randomized Controlled Trial. Ann Behav Med. 2016 Aug;50(4):554-63. doi: 10.1007/s12160-016-9782-z. **PMID:** 26896305 **Citation:** Winters-Stone KM, Boisvert C, Li F, Lyons KS, Beer TM, Mitri Z, Meyers G, Eckstrom E, Campbell KL. Delivering exercise medicine to cancer survivors: has COVID-19 shifted the landscape for how and who can be reached with supervised group exercise? Support Care Cancer. 2022 Mar;30(3):1903-1906. doi: 10.1007/s00520-021-06669-w. Epub 2021 Nov 6. **PMID:** 34741653 **Citation:** Borg GA. Psychophysical bases of perceived exertion. Med Sci Sports Exerc. 1982;14(5):377-81. **PMID:** 7154893 **Citation:** Borg, G. Borg's Perceived Exertion and Pain Scales. (Human Kinetics, Champaign, IL, 1998). **Citation:** Thorup CB, Gronkjaer M, Spindler H, Andreasen JJ, Hansen J, Dinesen BI, Nielsen G, Sorensen EE. Pedometer use and self-determined motivation for walking in a cardiac telerehabilitation program: a qualitative study. BMC Sports Sci Med Rehabil. 2016 Aug 18;8:24. doi: 10.1186/s13102-016-0048-7. eCollection 2016. **PMID:** 27547404 **Citation:** Pudkasam S, Polman R, Pitcher M, Fisher M, Chinlumprasert N, Stojanovska L, Apostolopoulos V. Physical activity and breast cancer survivors: Importance of adherence, motivational interviewing and psychological health. Maturitas. 2018 Oct;116:66-72. doi: 10.1016/j.maturitas.2018.07.010. Epub 2018 Jul 23. **PMID:** 30244781 **Citation:** Pudkasam S, Feehan J, Talevski J, Vingrys K, Polman R, Chinlumprasert N, Stojanovska L, Apostolopoulos V. Motivational strategies to improve adherence to physical activity in breast cancer survivors: A systematic review and meta-analysis. Maturitas. 2021 Oct;152:32-47. doi: 10.1016/j.maturitas.2021.06.008. Epub 2021 Jun 24. **PMID:** 34674806 **Citation:** Tremblay MS, Aubert S, Barnes JD, Saunders TJ, Carson V, Latimer-Cheung AE, Chastin SFM, Altenburg TM, Chinapaw MJM; SBRN Terminology Consensus Project Participants. Sedentary Behavior Research Network (SBRN) - Terminology Consensus Project process and outcome. Int J Behav Nutr Phys Act. 2017 Jun 10;14(1):75. doi: 10.1186/s12966-017-0525-8. **PMID:** 28599680 **Citation:** Cohen, J. Statistical Power Analysis for the Behavioral Sciences. (L. Erlbaum Associates, Hillsdale, N.J, 1988). **Citation:** Kang H. Sample size determination and power analysis using the G*Power software. J Educ Eval Health Prof. 2021;18:17. doi: 10.3352/jeehp.2021.18.17. Epub 2021 Jul 30. **PMID:** 34325496 **Citation:** Carraca EV, Rodrigues B, Franco S, Nobre I, Jeronimo F, Ilharco V, Gabriel F, Ribeiro L, Palmeira AL, Silva MN. Promoting physical activity through supervised vs motivational behavior change interventions in breast cancer survivors on aromatase inhibitors (PAC-WOMAN): protocol for a 3-arm pragmatic randomized controlled trial. BMC Cancer. 2023 Jul 5;23(1):632. doi: 10.1186/s12885-023-11137-1. **PMID:** 37407950 **Citation:** Hryniuk W, Bush H. The importance of dose intensity in chemotherapy of metastatic breast cancer. J Clin Oncol. 1984 Nov;2(11):1281-8. doi: 10.1200/JCO.1984.2.11.1281. No abstract available. **PMID:** 6387060 **Citation:** Van Vulpen JK, Velthuis MJ, Steins Bisschop CN, Travier N, Van Den Buijs BJ, Backx FJ, Los M, Erdkamp FL, Bloemendal HJ, Koopman M, De Roos MA, Verhaar MJ, Ten Bokkel-Huinink D, Van Der Wall E, Peeters PH, May AM. Effects of an Exercise Program in Colon Cancer Patients undergoing Chemotherapy. Med Sci Sports Exerc. 2016 May;48(5):767-75. doi: 10.1249/MSS.0000000000000855. **PMID:** 26694846 **Citation:** ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002 Jul 1;166(1):111-7. doi: 10.1164/ajrccm.166.1.at1102. No abstract available. Erratum In: Am J Respir Crit Care Med. 2016 May 15;193(10):1185. **PMID:** 12091180 **Citation:** Schmidt K, Vogt L, Thiel C, Jager E, Banzer W. Validity of the six-minute walk test in cancer patients. Int J Sports Med. 2013 Jul;34(7):631-6. doi: 10.1055/s-0032-1323746. Epub 2013 Feb 26. **PMID:** 23444095 **Citation:** But-Hadzic J, Dervisevic M, Karpljuk D, Videmsek M, Dervisevic E, Paravlic A, Hadzic V, Tomazin K. Six-Minute Walk Distance in Breast Cancer Survivors-A Systematic Review with Meta-Analysis. Int J Environ Res Public Health. 2021 Mar 5;18(5):2591. doi: 10.3390/ijerph18052591. **PMID:** 33807611 **Citation:** Rikli RE, Jones CJ. Development and validation of criterion-referenced clinically relevant fitness standards for maintaining physical independence in later years. Gerontologist. 2013 Apr;53(2):255-67. doi: 10.1093/geront/gns071. Epub 2012 May 20. **PMID:** 22613940 **Citation:** Hoenemeyer TW, Cole WW, Oster RA, Pekmezi DW, Pye A, Demark-Wahnefried W. Test/Retest Reliability and Validity of Remote vs. In-Person Anthropometric and Physical Performance Assessments in Cancer Survivors and Supportive Partners. Cancers (Basel). 2022 Feb 21;14(4):1075. doi: 10.3390/cancers14041075. **PMID:** 35205823 **Citation:** BECHTOL CO. Grip test; the use of a dynamometer with adjustable handle spacings. J Bone Joint Surg Am. 1954 Jul;36-A(4):820-4; passim. No abstract available. **PMID:** 13174611 **Citation:** Huang L, Liu Y, Lin T, Hou L, Song Q, Ge N, Yue J. Reliability and validity of two hand dynamometers when used by community-dwelling adults aged over 50 years. BMC Geriatr. 2022 Jul 15;22(1):580. doi: 10.1186/s12877-022-03270-6. **PMID:** 35840905 **Citation:** Polat K, Karadibak D, Guc ZGS, Yavuzsen T, Oztop I. The Relationship between Exercise Capacity and Muscle Strength, Physical Activity, Fatigue and Quality of Life in Patients with Cancer Cachexia. Nutr Cancer. 2024;76(1):55-62. doi: 10.1080/01635581.2023.2276486. Epub 2023 Dec 27. **PMID:** 37917566 **Citation:** Rosen B. Recovery of sensory and motor function after nerve repair. A rationale for evaluation. J Hand Ther. 1996 Oct-Dec;9(4):315-27. doi: 10.1016/s0894-1130(96)80037-8. **PMID:** 8994006 **Citation:** Paek J, Choi YJ. Association between hand grip strength and impaired health-related quality of life in Korean cancer survivors: a cross-sectional study. BMJ Open. 2019 Sep 8;9(9):e030938. doi: 10.1136/bmjopen-2019-030938. **PMID:** 31501128 **Citation:** Esteban-Simon A, Diez-Fernandez DM, Artes-Rodriguez E, Casimiro-Artes MA, Rodriguez-Perez MA, Moreno-Martos H, Casimiro-Andujar AJ, Soriano-Maldonado A. Absolute and Relative Handgrip Strength as Indicators of Self-Reported Physical Function and Quality of Life in Breast Cancer Survivors: The EFICAN Study. Cancers (Basel). 2021 Oct 21;13(21):5292. doi: 10.3390/cancers13215292. **PMID:** 34771456 **Citation:** Rikli, R. E. & Jones, C. J. Senior Fitness Test Manual. (Human Kinetics, United Kingdom, 2001). **Citation:** Kolber MJ, Hanney WJ. The reliability and concurrent validity of shoulder mobility measurements using a digital inclinometer and goniometer: a technical report. Int J Sports Phys Ther. 2012 Jun;7(3):306-13. **PMID:** 22666645 **Citation:** Yamada Y, Yoshida T, Murakami H, Kawakami R, Gando Y, Ohno H, Tanisawa K, Konishi K, Julien T, Kondo E, Nakagata T, Nanri H, Miyachi M. Phase angle obtained via bioelectrical impedance analysis and objectively measured physical activity or exercise habits. Sci Rep. 2022 Oct 14;12(1):17274. doi: 10.1038/s41598-022-21095-6. **PMID:** 36241873 **Citation:** Gil-Herrero L, Pollan M, Martin M, Lopez-Tarruella S, Castellanos M, Casla-Barrio S. The importance of physical exercise in cardiovascular fitness in breast cancer survivors. A cross-sectional study: women in Motion 2.0. Support Care Cancer. 2022 Aug;30(8):6745-6754. doi: 10.1007/s00520-022-06993-9. Epub 2022 May 6. **PMID:** 35524144 **Citation:** Khalil SF, Mohktar MS, Ibrahim F. The theory and fundamentals of bioimpedance analysis in clinical status monitoring and diagnosis of diseases. Sensors (Basel). 2014 Jun 19;14(6):10895-928. doi: 10.3390/s140610895. **PMID:** 24949644 **Citation:** Cotogni P, Monge T, Fadda M, De Francesco A. Bioelectrical impedance analysis for monitoring cancer patients receiving chemotherapy and home parenteral nutrition. BMC Cancer. 2018 Oct 17;18(1):990. doi: 10.1186/s12885-018-4904-6. **PMID:** 30332998 **Citation:** Baharudin, A. et al. Reliability, Technical Error of Measurement and Validity of Height Measurement Using Portable Stadiometer. (2017). **Citation:** Tudor-Locke C, Johnson WD, Katzmarzyk PT. Accelerometer-determined steps per day in US adults. Med Sci Sports Exerc. 2009 Jul;41(7):1384-91. doi: 10.1249/MSS.0b013e318199885c. **PMID:** 19516163 **Citation:** Lee PH, Macfarlane DJ, Lam TH, Stewart SM. Validity of the International Physical Activity Questionnaire Short Form (IPAQ-SF): a systematic review. Int J Behav Nutr Phys Act. 2011 Oct 21;8:115. doi: 10.1186/1479-5868-8-115. **PMID:** 22018588 **Citation:** Suau Q, Bianchini E, Bellier A, Chardon M, Milane T, Hansen C, Vuillerme N. Current Knowledge about ActiGraph GT9X Link Activity Monitor Accuracy and Validity in Measuring Steps and Energy Expenditure: A Systematic Review. Sensors (Basel). 2024 Jan 26;24(3):825. doi: 10.3390/s24030825. **PMID:** 38339541 **Citation:** Bassett DR Jr. Validity and Reliability issues in Objective Monitoring of Physical Activity. Res Q Exerc Sport. 2000 Jun;71 Suppl 2:30-6. doi: 10.1080/02701367.2000.11082783. No abstract available. **PMID:** 25680010 **Citation:** Bassett, D. R. & John, D. Use of pedometers and accelerometers in clinical populations: validity and reliability issues. Physical Therapy Reviews 15, 135-142 (2010). **Citation:** Trinh L, Motl RW, Roberts SA, Gibbons T, McAuley E. Estimation of physical activity intensity cut-points using accelerometry in breast cancer survivors and age-matched controls. Eur J Cancer Care (Engl). 2019 Sep;28(5):e13090. doi: 10.1111/ecc.13090. Epub 2019 May 20. **PMID:** 31106924 **Citation:** Troiano RP, Berrigan D, Dodd KW, Masse LC, Tilert T, McDowell M. Physical activity in the United States measured by accelerometer. Med Sci Sports Exerc. 2008 Jan;40(1):181-8. doi: 10.1249/mss.0b013e31815a51b3. **PMID:** 18091006 **Citation:** Watson KB, Carlson SA, Carroll DD, Fulton JE. Comparison of accelerometer cut points to estimate physical activity in US adults. J Sports Sci. 2014;32(7):660-9. doi: 10.1080/02640414.2013.847278. Epub 2013 Nov 5. **PMID:** 24188163 **Citation:** Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993 Mar 3;85(5):365-76. doi: 10.1093/jnci/85.5.365. **PMID:** 8433390 **Citation:** Bjelic-Radisic V, Cardoso F, Cameron D, Brain E, Kuljanic K, da Costa RA, Conroy T, Inwald EC, Serpentini S, Pinto M, Weis J, Morag O, Lindviksmoen Astrup G, Tomaszweksi KA, Pogoda K, Sinai P, Sprangers M, Aaronson N, Velikova G, Greimel E, Arraras J, Bottomley A; EORTC Quality of Life Group and Breast Cancer Group. An international update of the EORTC questionnaire for assessing quality of life in breast cancer patients: EORTC QLQ-BR45. Ann Oncol. 2020 Feb;31(2):283-288. doi: 10.1016/j.annonc.2019.10.027. Epub 2019 Dec 18. Erratum In: Ann Oncol. 2020 Apr;31(4):552. **PMID:** 31959345 **Citation:** Sprangers MA, Groenvold M, Arraras JI, Franklin J, te Velde A, Muller M, Franzini L, Williams A, de Haes HC, Hopwood P, Cull A, Aaronson NK. The European Organization for Research and Treatment of Cancer breast cancer-specific quality-of-life questionnaire module: first results from a three-country field study. J Clin Oncol. 1996 Oct;14(10):2756-68. doi: 10.1200/JCO.1996.14.10.2756. **PMID:** 8874337 **Citation:** Tsui TCO, Trudeau M, Mitsakakis N, Torres S, Bremner KE, Kim D, Davis AM, Krahn MD. Developing the Breast Utility Instrument, a preference-based instrument to measure health-related quality of life in women with breast cancer: Confirmatory factor analysis of the EORTC QLQ-C30 and BR45 to establish dimensions. PLoS One. 2022 Feb 4;17(2):e0262635. doi: 10.1371/journal.pone.0262635. eCollection 2022. **PMID:** 35120148 **Citation:** Imran M, Al-Wassia R, Alkhayyat SS, Baig M, Al-Saati BA. Assessment of quality of life (QoL) in breast cancer patients by using EORTC QLQ-C30 and BR-23 questionnaires: A tertiary care center survey in the western region of Saudi Arabia. PLoS One. 2019 Jul 10;14(7):e0219093. doi: 10.1371/journal.pone.0219093. eCollection 2019. **PMID:** 31291302 **Citation:** Curigliano G, Dunton K, Rosenlund M, Janek M, Cathcart J, Liu Y, Fasching PA, Iwata H. Patient-reported outcomes and hospitalization data in patients with HER2-positive metastatic breast cancer receiving trastuzumab deruxtecan or trastuzumab emtansine in the phase III DESTINY-Breast03 study. Ann Oncol. 2023 Jul;34(7):569-577. doi: 10.1016/j.annonc.2023.04.516. Epub 2023 May 12. **PMID:** 37179020 **Citation:** Trewick N, Neumann DL, Hamilton K. Effect of affective feedback and competitiveness on performance and the psychological experience of exercise within a virtual reality environment. PLoS One. 2022 Jun 8;17(6):e0268460. doi: 10.1371/journal.pone.0268460. eCollection 2022. **PMID:** 35675309 **Citation:** Baron RM, Kenny DA. The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations. J Pers Soc Psychol. 1986 Dec;51(6):1173-82. doi: 10.1037//0022-3514.51.6.1173. **PMID:** 3806354 **Citation:** Preacher KJ, Hayes AF. Asymptotic and resampling strategies for assessing and comparing indirect effects in multiple mediator models. Behav Res Methods. 2008 Aug;40(3):879-91. doi: 10.3758/brm.40.3.879. **PMID:** 18697684 **Citation:** World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013 Nov 27;310(20):2191-4. doi: 10.1001/jama.2013.281053. No abstract available. **PMID:** 24141714 **Citation:** Tunis SR, Stryer DB, Clancy CM. Practical clinical trials: increasing the value of clinical research for decision making in clinical and health policy. JAMA. 2003 Sep 24;290(12):1624-32. doi: 10.1001/jama.290.12.1624. **PMID:** 14506122 **Citation:** Lopez P, Galvao DA, Taaffe DR, Newton RU, Souza G, Trajano GS, Pinto RS. Resistance training in breast cancer patients undergoing primary treatment: a systematic review and meta-regression of exercise dosage. Breast Cancer. 2021 Jan;28(1):16-24. doi: 10.1007/s12282-020-01147-3. Epub 2020 Aug 19. **PMID:** 32815096 **Citation:** Scheede-Bergdahl C, Minnella EM, Carli F. Multi-modal prehabilitation: addressing the why, when, what, how, who and where next? Anaesthesia. 2019 Jan;74 Suppl 1:20-26. doi: 10.1111/anae.14505. **PMID:** 30604416 ## Document Section ### Large Document Module #### Large Docs - Date: 2024-04-29 - Filename: Prot_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: False - Label: Study Protocol - Size: 291458 - Type Abbrev: Prot - Upload Date: 2024-05-20T09:53 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000001941 - Term: Breast Diseases - ID: D000012871 - Term: Skin Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: All - Name: All Conditions - Abbrev: BXM - Name: Behaviors and Mental Disorders ### Condition Browse Module - Browse Leaves - ID: M5220 - Name: Breast Neoplasms - Relevance: HIGH - As Found: Breast Cancer - ID: M5218 - Name: Breast Diseases - Relevance: LOW - As Found: Unknown - ID: M15674 - Name: Skin Diseases - Relevance: LOW - As Found: Unknown - ID: T6034 - Name: Quality of Life - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001943 - Term: Breast Neoplasms ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429176 **Brief Title:** Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of SPL84 in Patients With Cystic Fibrosis **Official Title:** A Phase 2a, Randomized, Placebo-Controlled, Double Blind Multiple Ascending Dose Study in Patients With Cystic Fibrosis Carrying the 3849 +10 Kb C->T Mutation to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of SPL84 #### Organization Study ID Info **ID:** SPL84-002 #### Organization **Class:** INDUSTRY **Full Name:** SpliSense Ltd. #### Secondary ID Infos **ID:** 2024-511184-28 **Type:** EUDRACT_NUMBER ### Status Module #### Completion Date **Date:** 2025-12-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2025-10-01 **Type:** ESTIMATED #### Start Date **Date:** 2024-07-01 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Study First Submit Date:** 2024-05-15 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** SpliSense Ltd. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True ### Description Module **Brief Summary:** The goal of this clinical trial is to learn if drug SPL84 is safe for adult patients with cystic fibrosis (CF). It will also learn if the drug works to treat works to treat CF with a specific mutation. The purpose of this research study is to: * test the safety and effectiveness of multiple doses of the study drug, SPL84 * test how multiple doses of the drug are processed by the body Researchers will compare drug SPL84 to a placebo (a look-alike substance that contains no drug) to see if drug SPL84 is safe and if it works to treat CF. Participants will: Take drug SPL84 or a placebo by inhalation every week for 9 weeks months Visit the clinic approximately 14 times over 17.5 weeks for checkups and tests ### Conditions Module **Conditions:** - Cystic Fibrosis ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** SEQUENTIAL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 24 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Drug: SPL84 **Label:** SPL84 **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Intervention Names:** - Other: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - SPL84 **Description:** SPL84 solution for nebulization **Name:** SPL84 **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** Placebo solution for nebulization **Name:** Placebo **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Incidence, nature, and severity of AEs and SAEs **Measure:** Safety and Tolerability of SPL84 as evaluated by number of subjects with at least one treatment-related adverse event (AE) or serious adverse event (SAEs) **Time Frame:** Day 1 through Day 87 **Measure:** Safety and Tolerability of SPL84 as assessed by number of participants with abnormal heart rate **Time Frame:** Day 1 through Day 87 **Measure:** Safety and Tolerability of SPL84 as assessed by number of participants with abnormal respiratory rate **Time Frame:** Day 1 through Day 87 **Measure:** Safety and Tolerability of SPL84 as assessed by number of participants with abnormal systolic and diastolic blood pressure **Time Frame:** Day 1 through Day 87 **Measure:** Safety and Tolerability of SPL84 as assessed by number of participants with abnormal oximetry **Time Frame:** Day 1 through Day 87 **Measure:** Safety and Tolerability of SPL84 as assessed by number of participants with abnormal temperature **Time Frame:** Day 1 through Day 87 **Measure:** Safety and Tolerability of SPL84 as assessed by number of participants with abnormal hematology lab test results **Time Frame:** Day 1 through Day 87 **Measure:** Safety and Tolerability of SPL84 as assessed by number of participants with abnormal biochemistry lab test results **Time Frame:** Day 1 through Day 87 **Measure:** Safety and Tolerability of SPL84 as assessed by number of participants with abnormal urinalysis lab test results **Time Frame:** Day 1 through Day 87 **Description:** using an ECG machine that automatically calculates heart rate and measure PR, QRS, QT, and QTc intervals **Measure:** Safety and Tolerability of SPL84 as assessed by number of participants with abnormal electrocardiogram (ECG) parameters **Time Frame:** Day 1 through Day 87 **Description:** Complete physical examinations include general appearance, head, ears, eyes, nose, throat, thyroid, chest (heart, lungs), abdomen, skin, neurological, extremities, back, neck, musculoskeletal, and lymph nodes. **Measure:** Safety and Tolerability of SPL84 as assessed by number of participants with abnormal physical examination findings **Time Frame:** Day 1 through Day 87 **Description:** Pulmonary function tests will be performed according to the American Thoracic Society (ATS)/European Respiratory Society (ERS) and forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and forced mid-expiratory flow (FEF25-75) will be measured **Measure:** Safety and Tolerability of SPL84 as assessed by number of participants with abnormal pulmonary function tests results **Time Frame:** Day 1 through Day 87 **Description:** Sputum microbiology will be performed with a microbiology based assay; organism growth will be identified. **Measure:** Safety and Tolerability of SPL84 as assessed by number of participants with abnormal sputum microbiology results results **Time Frame:** Day 1 through Day 87 **Description:** assessment of anti-SPL84 antibodies will be performed both in serum and sputum **Measure:** Safety and Tolerability of SPL84 as assessed by number of participants with abnormal immunogenicity results **Time Frame:** Day 1 through Day 87 #### Secondary Outcomes **Measure:** Characterization of pharmacokinetics (PK) of SPL84: maximum serum concentration (Cmax) **Time Frame:** Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87 **Measure:** Characterization of PK of SPL84: Time to Cmax (Tmax) **Time Frame:** Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87 **Measure:** Characterization of PK of SPL84: terminal elimination half-life (t1/2) **Time Frame:** Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87 **Measure:** Characterization of PK of SPL84: Area under the curve to the final sample (AUC0-t) **Time Frame:** Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87 **Measure:** Characterization of PK of SPL84: Area under the curve to infinity (AUC0-∞) **Time Frame:** Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87 **Measure:** Characterization of PK of SPL84: Apparent clearance (CL/F) **Time Frame:** Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87 **Measure:** Characterization of excretion of SPL84: concentration of SPL84 in urine **Time Frame:** Day 1 through Day 87 **Description:** Pulmonary function tests will be performed according to the ATS/ERS **Measure:** Preliminary efficacy of SPL84 as assessed by change from baseline in percent predicted FEV1 **Time Frame:** Day 1 through Day 87 **Description:** The score for is standardized on a 0- to 100-point scale on which higher scores represent a higher quality of life **Measure:** Preliminary efficacy of SPL84 as assessed by change from baseline in Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Score **Time Frame:** Day 1 through Day 87 **Measure:** Preliminary efficacy of SPL84 as assessed by change from baseline in body weight **Time Frame:** Day 1 through Day 87 **Measure:** Preliminary efficacy of SPL84 as assessed by change from baseline of antibiotic treatment **Time Frame:** Day 1 through Day 87 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Diagnosis of CF and two CF causing mutations; 3849+10 Kb C-\>T mutation on one allele in the CF transmembrane conductance regulator (CFTR) gene (homozygote or compound heterozygote). Source documentation from a certified genetic laboratory is required. * Body mass index (BMI) of ≥ 17 kg/m2. * FEV1 40-90% predicted at screening. * Non-smokers or vapers for at least 180 days (6 months) prior to screening, per participant report. Exclusion Criteria: * Use of Kalydeco, Orkambi, Symdeko/Symkevi or Trikafta/Kaftrio within 30 days of first dose with study intervention. * Use of any investigational drug (other than SPL84) or device within 30 days of first dose with study intervention. * Use of systemic steroids over 3 consecutive months in the last 6 months prior to screening, or use of systemic steroids in the last month prior to screening. Use of inhaled steroids above 1 mg. * Use of CF medications, e.g. inhaled antibiotics, dornase alfa (Pulmozyme), hypertonic saline and physiotherapy should be on stable regimen for the period 28 days prior to screening; those participants taking inhaled antibiotics for prophylaxis must be on a stable regimen of these drugs for at least 90 days prior to first dose with study intervention. * Any acute infection including acute upper respiratory or lower respiratory infections, pulmonary exacerbation, changes in therapy for pulmonary disease, or any non CF-related illness which results in the initiation of any new therapy within 14 days prior to first dose with study intervention. * Hemoptysis of greater than 30 mL within 90 days prior to Day 1, or hospitalization for hemoptysis within 6 months of first dose with study intervention. * Liver disease characterized by clinically significant cirrhosis and/or documented portal hypertension. * History of any organ transplantation. * Documented coronavirus disease (COVID-19) infection within 4 weeks prior to dosing. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Birmingham **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Kathryn Monroe - **Phone:** 205-638-5599 - **Role:** CONTACT **Country:** United States **Facility:** University of Alabama at Birmingham **State:** Alabama **Status:** RECRUITING **Zip:** 35233 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000010182 - Term: Pancreatic Diseases - ID: D000004066 - Term: Digestive System Diseases - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases - ID: D000030342 - Term: Genetic Diseases, Inborn - ID: D000007232 - Term: Infant, Newborn, Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M8485 - Name: Fibrosis - Relevance: HIGH - As Found: Fibrosis - ID: M6755 - Name: Cystic Fibrosis - Relevance: HIGH - As Found: Cystic Fibrosis - ID: M13102 - Name: Pancreatic Diseases - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: M23686 - Name: Genetic Diseases, Inborn - Relevance: LOW - As Found: Unknown - ID: M10276 - Name: Infant, Newborn, Diseases - Relevance: LOW - As Found: Unknown - ID: T1710 - Name: Cystic Fibrosis - Relevance: HIGH - As Found: Cystic Fibrosis ### Condition Browse Module - Meshes - ID: D000003550 - Term: Cystic Fibrosis - ID: D000005355 - Term: Fibrosis ### Intervention Browse Module - Browse Branches - Abbrev: PhSol - Name: Pharmaceutical Solutions - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M21860 - Name: Pharmaceutical Solutions - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429163 **Acronym:** WINPLEX **Brief Title:** Pre-incisional Wound INfiltration and Hypogastric PLEXus Block Using Ropivacaine in Laparoscopic Myomectomy **Official Title:** Влияние прединцизионной инфильтрации ран и блокады гипогастрального нервного сплетения с использованием ропивакаина на болевой синдром после лапароскопической миомэктомии. Одноцентровое проспективное рандомизированное плацебо-контролируемое двойное слепое экспериментальное исследование #### Organization Study ID Info **ID:** WINPLEX #### Organization **Class:** OTHER **Full Name:** Saint Petersburg State University, Russia ### Status Module #### Completion Date **Date:** 2024-11-04 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-29 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-27 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-11-01 **Type:** ESTIMATED #### Start Date **Date:** 2024-05-14 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Study First Submit Date:** 2024-05-14 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Saint Petersburg State University, Russia #### Responsible Party **Investigator Affiliation:** Saint Petersburg State University, Russia **Investigator Full Name:** Nikita Kharlov **Investigator Title:** Head of Gynecology department **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** The purpose of this study is to evaluate the effectiveness of a comprehensive approach to anesthesia in patients with uterine myoma using pre-incisional infiltration of the anterior abdominal wall and presacral blockade of the hypogastric nerve plexus during laparoscopic myomectomy **Detailed Description:** On admission, patients will complete the EQ-5D quality of life questionnaire to assess the level of problems including pain, anxiety and depression, as well as the level of quality of life in general. The Central Sensitization Inventory (CSI-R) is also completed. Each patient is randomly assigned to one of three groups on admission: standard variant of postoperative analgesia (systemic administration - intravenous, intramuscular, oral - non-steroidal anti-inflammatory drugs, paracetamol, opioid analgesics), prophylactic pre-incisional infiltration of the anterior abdominal wall + standard variant of postoperative analgesia or prophylactic pre-incisional infiltration of the anterior abdominal wall + presacral blockade + standard variant of postoperative analgesia. Randomisation is done in a 1:1:1 ratio. In the early postoperative period, a questionnaire is administered to patients to determine the intensity and nature of pain: hourly VAS value, localisation of pain and conditions of its onset are noted. At discharge, patients fill out the EQ-5D questionnaire and the Picker questionnaire to assess the patient's impressions of her hospital stay. ### Conditions Module **Conditions:** - Fibroid Uterus - Pain, Postoperative **Keywords:** - Uterine fibroid - Laparoscopic myomectomy - Postoperative pain - Pre-incisional infiltration - Hypogastric plexus block - EQ-5D questionnaire - Picker questionnaire - The Central Sensitization Inventory (CSI-R) ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** A single-centre prospective randomized placebo-controlled double-blind pilot study ##### Masking Info **Masking:** DOUBLE **Masking Description:** All patients and clinicians involved in the study are unaware of the group assignment and syringe contents. **Who Masked:** - PARTICIPANT - CARE_PROVIDER **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 198 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Standard variant of postoperative analgesia (systemic administration - intravenous, intramuscular, oral - non-steroidal anti-inflammatory drugs, paracetamol, opioid analgesics). **Intervention Names:** - Procedure: Infiltration of the anterior abdominal wall - Procedure: Upper hypogastric plexus blockade **Label:** Standart analgesia **Type:** PLACEBO_COMPARATOR #### Arm Group 2 **Description:** Prophylactic pre-incisional infiltration of the anterior abdominal wall + standard variant of postoperative analgesia **Intervention Names:** - Procedure: Infiltration of the anterior abdominal wall **Label:** Pre-incisional infiltration **Type:** ACTIVE_COMPARATOR #### Arm Group 3 **Description:** Prophylactic pre-incisional infiltration of the anterior abdominal wall + presacral blockade + standard variant of postoperative analgesia **Intervention Names:** - Procedure: Upper hypogastric plexus blockade **Label:** Presacral blockade **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Pre-incisional infiltration - Standart analgesia **Description:** Infiltration of the anterior abdominal wall is performed with 0.2% ropivacaine diluted with physiological saline on a syringe in the volume of 20 ml - 5 ml for each incision. The drug is injected with a 22-gauge needle at a 90-degree angle. **Name:** Infiltration of the anterior abdominal wall **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - Presacral blockade - Standart analgesia **Description:** At the beginning of the operation the camera is used to visualise the area of the promontorium. Next, a 1 mm laparoscopic puncture needle is inserted through a trocar in the suprapubic region and plunged into the upper part of the formed dome to a depth of no more than 1 cm. After positioning the needle retroperitoneally, an aspiration test is performed to prevent intravascular injection. Then, 20 ml of 0.2% ropivacaine diluted with physiological saline is slowly injected. At the end of the procedure, the retroperitoneal space swollen by the local anaesthetic is visualised in the promontorium. **Name:** Upper hypogastric plexus blockade **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** Frequency of severe pain syndrome (≥ 4 points on the visual analogue scale) in the postoperative period after laparoscopic conservative myomectomy. **Measure:** Frequency of severe pain syndrome **Time Frame:** In the postoperative period, an average of 2 days #### Secondary Outcomes **Description:** Timing of post-surgery mobilization (hours after surgery) **Measure:** Mobilization **Time Frame:** In the early postoperative period, an average of 24 hours **Description:** Frequency of opioid analgesic requirements **Measure:** Opioid analgesic **Time Frame:** In the early postoperative period, an average of 24 hours **Description:** A questionnaire is administered to patients to determine the nature of pain: localisation of pain and conditions of its onset are noted The questionnaire indicates the localisation of pain (anterior abdominal wall, small pelvis, right shoulder), the conditions of its occurrence (lying, standing, and during the stress test). **Measure:** Localisation of pain syndrome **Time Frame:** In the postoperative period, an average of 2 days **Description:** patients fill out the EQ-5D questionnaire to assess the patient's impressions of her hospital stay. EQ-5D is a multidimensional tool for assessing the quality of life, which can be expressed using a single indicator - an index. In this regard, it is also called a health index. Each component is divided into three levels according to the severity of the problem: no problem, moderately severe problem, severe problem. Combining these levels in five components allows to get 243 variants of 'health status'. The second part of the questionnaire is a visual analogue scale, the so-called 'health thermometer'. This is a twenty-centimetre vertical graduated ruler with 0 representing the worst and 100 representing the best state of health. **Measure:** Patients' satisfaction level **Time Frame:** At discharge, an average 2 days after surgery **Description:** The Picker Patient Experience Questionnaire is designed for patient evaluation of 7 aspects of care: information, consistency, psychological aspect, consideration of patient preferences, physical well-being, involvement of family and friends, and continuity of care laparoscopic myomectomy performed. The total score is calculated as a percentage (0 - no problem in any aspect, 100 - presence of problems in all domains). **Measure:** level of problems on different aspects of functioning **Time Frame:** At discharge, an average 2 days after surgery ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * patients with large nodal (≥ 6 cm) and/or multiple uterine myomas who are indicated for surgical treatment in the scope of laparoscopic myomectomy on the basis of the gynaecological department of the Pirogov Gynecological Centre of St. Petersburg State University, * age - 18 years and over, * informed consent of patients to participate in the research study Exclusion Criteria: * conversion to laparotomy, * subserous uterine myoma 'on a pedicle' (type 7 according to FIGO), * the start of the surgical intervention is after 15.00, * presence of malignant diseases, diabetes mellitus, external genital endometriosis of 3-4 stage, * presence of psychiatric and cognitive impairment in female patients that, in the opinion of the physician, precludes participation in the study, * the need for abdominal drainage, * severe adhesions in the sacral region **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Saint Petersburg **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Nikita Kharlov - **Phone:** 89262839377 - **Role:** CONTACT **Country:** Russian Federation **Facility:** Saint Petersburg State University Hospital **Status:** RECRUITING ## Derived Section ### Condition Browse Module - Ancestors - ID: D000011183 - Term: Postoperative Complications - ID: D000010335 - Term: Pathologic Processes - ID: D000010146 - Term: Pain - ID: D000009461 - Term: Neurologic Manifestations - ID: D000009379 - Term: Neoplasms, Muscle Tissue - ID: D000018204 - Term: Neoplasms, Connective and Soft Tissue - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000009372 - Term: Neoplasms, Connective Tissue - ID: D000003240 - Term: Connective Tissue Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: BC10 - Name: Nervous System Diseases ### Condition Browse Module - Browse Leaves - ID: M13069 - Name: Pain, Postoperative - Relevance: HIGH - As Found: Pain, Postoperative - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown - ID: M10901 - Name: Leiomyoma - Relevance: HIGH - As Found: Fibroid Uterus - ID: M25846 - Name: Myofibroma - Relevance: HIGH - As Found: Fibroid Uterus - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M14065 - Name: Postoperative Complications - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: M20350 - Name: Neoplasms, Connective and Soft Tissue - Relevance: LOW - As Found: Unknown - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M12317 - Name: Neoplasms, Connective Tissue - Relevance: LOW - As Found: Unknown - ID: M6464 - Name: Connective Tissue Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007889 - Term: Leiomyoma - ID: D000047708 - Term: Myofibroma - ID: D000010149 - Term: Pain, Postoperative ### Intervention Browse Module - Browse Branches - Abbrev: Infl - Name: Anti-Inflammatory Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: Analg - Name: Analgesics - Abbrev: ARhu - Name: Antirheumatic Agents ### Intervention Browse Module - Browse Leaves - ID: M4217 - Name: Anti-Inflammatory Agents - Relevance: LOW - As Found: Unknown - ID: M4107 - Name: Anesthetics - Relevance: LOW - As Found: Unknown - ID: M4032 - Name: Analgesics - Relevance: LOW - As Found: Unknown - ID: M1700 - Name: Ropivacaine - Relevance: LOW - As Found: Unknown - ID: M4109 - Name: Anesthetics, Local - Relevance: LOW - As Found: Unknown - ID: M4033 - Name: Analgesics, Opioid - Relevance: LOW - As Found: Unknown - ID: M4218 - Name: Anti-Inflammatory Agents, Non-Steroidal - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429150 **Brief Title:** Frontline Combination CAR-T Cell Therapy for Multiple Myeloma or Plasmacytoma **Official Title:** Frontline Management of High-Risk Multiple Myeloma or Plasmacytoma With BCMA and GPRC5D Combination CAR-T Cell Therapy #### Organization Study ID Info **ID:** GIMI-IRB-24001 #### Organization **Class:** OTHER **Full Name:** Shenzhen Geno-Immune Medical Institute ### Status Module #### Completion Date **Date:** 2027-12-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2027-07-11 **Type:** ESTIMATED #### Start Date **Date:** 2024-05-11 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Study First Submit Date:** 2024-05-14 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** The No.2 Clinical Hospital of the Ministry of Health #### Lead Sponsor **Class:** OTHER **Name:** Shenzhen Geno-Immune Medical Institute #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The aim of this clinical trial is to assess the feasibility, safety, and efficacy of CAR-T cell therapy targeting multiple cancer cell antigens in high-risk multiple myeloma or plasmacytoma as part of a frontline treatment regimen for patients. Another goal of the study is to learn more about the persistence and function of these CAR-T cells in the body. **Detailed Description:** Multiple myeloma (MM) is the second most common malignant hematological cancer in the world, which begins with the malignant proliferation of plasma cells in bone marrow. It has been a difficult disease to treat, and most patients will eventually relapse, especially for those with high-risk genotypes. At present, the therapeutic drugs for MM include glucocorticoids, cytotoxic drugs, immunosuppressants, protease inhibitors, monoclonal antibodies and cell therapies. Among those, immunotherapy has been proven to be a revolutionary treatment with great potential of curing this disease. The frequently targeted MM antigens include CD38, CD138, CD19 and BCMA, and recently, GPRC5D. BCMA, the B cell maturation antigen, also known as CD269 or TNFRSF17, is a member of tumor necrosis factor receptor superfamily, which is highly expressed on the surface of plasma cells and partially expressed on plasma cell-like dendritic cells. It has been an ideal target for MM immunotherapy. GPRC5D, the G-protein-coupled receptor C57 subtype D and a seven-transmembrane protein, is highly expressed on the surface of plasma cells but not in other healthy cells, and thus it has become a potential target for the treatment of MM. The expression of GPRC5D is unrelated to BCMA, so the combination therapy targeting these antigens may bring a complementary and synergistic therapeutic outcome in patients. This trial is aimed to test the safety and efficacy of combining these different CAR-T cells targeting BCMA and GPRC5D, and in combination with well-established therapeutics as a frontline treatment for the high-risk MM or plasmacytoma patients. Another goal of this study is to investigate the persistence and function of these CAR-T cells in the body. ### Conditions Module **Conditions:** - Multiple Myeloma - Plasmacytoma **Keywords:** - multiple myeloma - chimeric antigen receptor - BCMA - GPRC5D ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 20 **Type:** ESTIMATED **Phases:** - PHASE1 - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Biological: CAR-T cells **Label:** CAR-T cells to treat MM **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - CAR-T cells to treat MM **Description:** Infusion of multi-CAR-T cells **Name:** CAR-T cells **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Description:** The percentage of participants with treatment-related adverse events, as assessed by CTCAE v4.0 **Measure:** Percentage of patients with treatment related adverse effects **Time Frame:** 1 month #### Secondary Outcomes **Description:** Anti-tumor activity of the fourth generation multiple CAR-T cells after infusion by measuring the CAR copies in the blood **Measure:** Anti-tumor activity of the fourth generation multiple CAR-T cells after infusion **Time Frame:** 1 year **Description:** Anti-tumor activity of fourth generation multiple CAR-T cells in patients with high-risk MM or plasmacytoma by examination of known tumor indicators **Measure:** Anti-tumor activity of fourth generation multiple CAR-T cells in patients with high-risk MM or plasmacytoma **Time Frame:** 1 year ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Male and female subjects with multiple myeloma or plasmacytoma * Strictly complete remission (sCR) is a treatment goal * Expected survival \> 12 weeks * After prior auto-SCT is eligible regardless of other prior therapies * Adequate venous access for apheresis, and no other contraindications for leukapheresis * Voluntary informed consent is given and commitment to continued follow-up Exclusion Criteria: * Pregnant or lactating women * Uncontrolled active infection * Active HIV, hepatitis B or hepatitis C infection * Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary. * Any medical conditions that may preclude participation **Maximum Age:** 80 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Lung-Ji Chang, ph.D **Phone:** 86-0755 86725195 **Role:** CONTACT #### Locations **Location 1:** **City:** Shenzhen **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Lung-Ji Chang, ph.D - **Phone:** 86-0755-86725195 - **Role:** CONTACT ***Contact 2:*** - **Name:** Vitaly Dubov, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** China **Facility:** Shenzhen Geno-immune Medical Institute **State:** Guangdong **Status:** RECRUITING **Zip:** 518000 **Location 2:** **City:** Vladivostok **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Vitaly Dubov, MD - **Phone:** 8(924)3321996 - **Role:** CONTACT **Country:** Russian Federation **Facility:** Hematologist of the Regional Hematology Center in Clinical Hospital No. 2 of the Ministry of Health **Status:** RECRUITING **Zip:** 690105 ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000020141 - Term: Hemostatic Disorders - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000010265 - Term: Paraproteinemias - ID: D000001796 - Term: Blood Protein Disorders - ID: D000006402 - Term: Hematologic Diseases - ID: D000006474 - Term: Hemorrhagic Disorders - ID: D000008232 - Term: Lymphoproliferative Disorders - ID: D000007160 - Term: Immunoproliferative Disorders - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M12058 - Name: Multiple Myeloma - Relevance: HIGH - As Found: Multiple Myeloma - ID: M27588 - Name: Neoplasms, Plasma Cell - Relevance: HIGH - As Found: Multiple Myeloma - ID: M13844 - Name: Plasmacytoma - Relevance: HIGH - As Found: Plasmacytoma - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M21977 - Name: Hemostatic Disorders - Relevance: LOW - As Found: Unknown - ID: M5059 - Name: Blood Coagulation Disorders - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: M13178 - Name: Paraproteinemias - Relevance: LOW - As Found: Unknown - ID: M5077 - Name: Blood Protein Disorders - Relevance: LOW - As Found: Unknown - ID: M9490 - Name: Hematologic Diseases - Relevance: LOW - As Found: Unknown - ID: M9560 - Name: Hemorrhagic Disorders - Relevance: LOW - As Found: Unknown - ID: M11225 - Name: Lymphoproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: M10206 - Name: Immunoproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown - ID: T3947 - Name: Multiple Myeloma - Relevance: HIGH - As Found: Multiple Myeloma - ID: T4587 - Name: Plasmacytoma - Relevance: HIGH - As Found: Plasmacytoma ### Condition Browse Module - Meshes - ID: D000009101 - Term: Multiple Myeloma - ID: D000054219 - Term: Neoplasms, Plasma Cell - ID: D000010954 - Term: Plasmacytoma ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429137 **Brief Title:** A Study in Healthy Men to Test How Well Different Doses of BI 3731579 Are Tolerated **Official Title:** A Partially Randomised, Single-blind, Placebo-controlled Trial to Investigate Safety, Tolerability, and Pharmacokinetics of Single Rising Doses of BI 3731579 Administered as Tablet to Healthy Male Subjects #### Organization Study ID Info **ID:** 1519-0001 #### Organization **Class:** INDUSTRY **Full Name:** Boehringer Ingelheim #### Secondary ID Infos **Domain:** CTIS **ID:** 2023-510318-25-00 **Type:** REGISTRY **Domain:** WHO International Clinical Trials Registry Platform (ICTRP) **ID:** U1111-1304-0523 **Type:** REGISTRY ### Status Module #### Completion Date **Date:** 2024-10-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-29 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-27 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2024-10-31 **Type:** ESTIMATED #### Start Date **Date:** 2024-06-26 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Study First Submit Date:** 2024-05-21 **Study First Submit QC Date:** 2024-05-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Boehringer Ingelheim #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The main objectives of this trial are to investigate safety, tolerability and pharmacokinetics (PK) of BI 3731579 in healthy male subjects. ### Conditions Module **Conditions:** - Healthy ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - PARTICIPANT **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 64 **Type:** ESTIMATED **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Drug: BI 3731579 **Label:** BI 3731579 dose group 1 **Type:** EXPERIMENTAL #### Arm Group 2 **Intervention Names:** - Drug: BI 3731579 **Label:** BI 3731579 dose group 2 **Type:** EXPERIMENTAL #### Arm Group 3 **Intervention Names:** - Drug: BI 3731579 **Label:** BI 3731579 dose group 3 **Type:** EXPERIMENTAL #### Arm Group 4 **Intervention Names:** - Drug: BI 3731579 **Label:** BI 3731579 dose group 4 **Type:** EXPERIMENTAL #### Arm Group 5 **Intervention Names:** - Drug: BI 3731579 **Label:** BI 3731579 dose group 5 **Type:** EXPERIMENTAL #### Arm Group 6 **Intervention Names:** - Drug: BI 3731579 **Label:** BI 3731579 dose group 6 **Type:** EXPERIMENTAL #### Arm Group 7 **Intervention Names:** - Drug: BI 3731579 **Label:** BI 3731579 dose group 7 **Type:** EXPERIMENTAL #### Arm Group 8 **Intervention Names:** - Drug: BI 3731579 **Label:** BI 3731579 dose group 8 **Type:** EXPERIMENTAL #### Arm Group 9 **Intervention Names:** - Drug: Matching placebo to BI 3731579 **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - BI 3731579 dose group 1 - BI 3731579 dose group 2 - BI 3731579 dose group 3 - BI 3731579 dose group 4 - BI 3731579 dose group 5 - BI 3731579 dose group 6 - BI 3731579 dose group 7 - BI 3731579 dose group 8 **Description:** BI 3731579 **Name:** BI 3731579 **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** Matching placebo to BI 3731579 **Name:** Matching placebo to BI 3731579 **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Occurrence of any treatment-emergent adverse event assessed as drug-related by the investigator **Time Frame:** up to 14 days #### Secondary Outcomes **Measure:** Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) **Time Frame:** up to 4 days **Measure:** Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) **Time Frame:** up to 4 days **Measure:** Maximum measured concentration of the analyte in plasma (Cmax) **Time Frame:** up to 4 days ### Eligibility Module **Eligibility Criteria:** Inclusion criteria 1. Healthy male subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), and clinical laboratory tests 2. Age of 18 to 45 years (inclusive) 3. Body mass index (BMI) of 18.5 to 29.9 kg/m\^2 (inclusive) 4. Signed and dated written informed consent in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial Exclusion criteria 1. Any finding in the medical examination (including BP, PR or ECG) deviating from normal and assessed as clinically relevant by the investigator 2. Repeated measurement of systolic blood pressure outside the range of 90 to 140 millimeter of mercury (mmHg), diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 to 90 beats per minute (bpm) 3. Any laboratory value outside the reference range that the investigator considers to be of clinical relevance 4. Any evidence of a concomitant disease assessed as clinically relevant by the investigator Further exclusion criteria apply **Healthy Volunteers:** True **Maximum Age:** 45 Years **Minimum Age:** 18 Years **Sex:** MALE **Standard Ages:** - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Boehringer Ingelheim **Phone:** 1-800-243-0127 **Role:** CONTACT ### IPD Sharing Statement Module **Description:** Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datatransparency **IPD Sharing:** NO ### References Module #### See Also Links **Label:** Related Info **URL:** http://www.mystudywindow.com ## Derived Section ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429124 **Acronym:** TREAD **Brief Title:** Time Restricted Eating in Alzheimer's Disease (TREAD) **Official Title:** Time-Restricted Eating in Alzheimer's Disease : The T.R.E.A.D Trial #### Organization Study ID Info **ID:** HX-23-500-347-30-03 #### Organization **Class:** OTHER **Full Name:** St. Joseph's Hospital and Medical Center, Phoenix ### Status Module #### Completion Date **Date:** 2026-03-14 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-06-05 **Type:** ACTUAL **Last Update Submit Date:** 2024-06-03 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2025-03-14 **Type:** ESTIMATED #### Start Date **Date:** 2023-03-15 **Type:** ACTUAL **Status Verified Date:** 2024-06 #### Study First Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Study First Submit Date:** 2024-04-29 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Arizona State University **Class:** OTHER **Name:** Karlsruhe Institute of Technology **Class:** OTHER **Name:** Mayo Clinic #### Lead Sponsor **Class:** OTHER **Name:** St. Joseph's Hospital and Medical Center, Phoenix #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** This pilot and feasibility study will enable the research team to determine the feasibility of implementing a time-restricted eating regimen among adults with mild cognitive impairment (MCI) and the impact of time-restricted eating on cognitive performance and biomarkers of metabolic health in this population. Study staff will execute the specific aims using a pre-post, non-randomized study design in which all participants receive the intervention. The intervention is a 16/8 time-restricted eating regimen characterized by fasting for 16 hours and eating within an 8-hour window on 5 days per week for 3 months. Assessments will be performed at baseline and after the 3-month time-restricted eating intervention with the following outcome measures. Outcome measures for feasibility include participant recruitment, retention and metrics of acceptability, safety, and adherence to the intervention. Outcome measures for cognitive performance and metabolic health include neuropsychological tests, blood biomarkers, and surveys of psychological well-being. **Detailed Description:** The goal of this pilot study on time restricted eating regimens in the mild cognitive impairment (MCI) patient population will be to determine the feasibility of implementing the intervention and impact of time-restricted eating on cognitive performance and biomarkers of metabolic health. Researchers at the Barrow Neurological Institute, Alzheimer\&amp;#39;s Disease Program in collaboration with the Arizona State University College of Health Solutions will execute the specific aims using a pre-post non-randomized study design in which all participants receive the intervention. Outcome assessments for specific aim 2 will include neuropsychological tests, blood biomarkers, and psychological well-being measured at baseline and after 3 months of intervention. Participants will be instructed to follow a 16/8 regimen characterized by 16 hours of fasting and an 8-hour eating window daily, on approximately 5 days/week, for 3 months. Primary outcomes will include participant recruitment, retention, acceptability, safety, and adherence to the 16 hours of fasting and 8-hour eating window. Researchers hypothesize that participants who follow a time-restricted eating pattern will have improvements in attention, working memory and semantic fluency domains. Study staff hypothesize that there will be improvements or trends toward improvements in inflammatory and cardiometabolic biomarkers (i.e., interleukin-6, tumor necrosis factor alpha, C-reactive protein, insulin, hemoglobin A1c, and lipids). The results of this project will provide critical preliminary data for a longer-term, large-scale, randomized controlled trial of time-restricted eating on cognitive trajectory among adults with MCI. The novel findings from the proposed project and future studies will contribute significantly to the body of knowledge that will advance the field, with the ultimate goal of preventing or delaying the progression of MCI to dementia. ### Conditions Module **Conditions:** - Intermittent Fasting **Keywords:** - Alzheimer's Disease - Mild Cognitive Impairment - Intermittent Fasting - Nutritional Strategies - Time Restricted Eating ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP **Intervention Model Description:** We will execute the specific aims using a pre-post non-randomized study design in which all participants receive the intervention. Outcome assessments for specific aim 2 will include neuropsychological tests, blood biomarkers, and psychological well-being measured at baseline and after 3 months of intervention. ##### Masking Info **Masking:** NONE **Masking Description:** This study will not use any masking. **Primary Purpose:** OTHER #### Enrollment Info **Count:** 30 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants will be instructed to follow a 16/8 regimen characterized by 16 hours of fasting and an 8-hour eating window daily, on approximately 5 days/week, for 3 months. Previous research has shown that 16 hours of fasting is feasible, safe and well-tolerated among older adults, and that most persons report easy adjustment (Anton, Lee et al. 2019, Lee, Sypniewski et al. 2020). The intervention will be implemented through individual and group sessions with participants and will involve extensive education, coaching, guidance, and support throughout the 3-month intervention. Educational materials on lifestyle factors including physical activity will be provided to each participant. We will be also be collecting data on physical activity and sedentary behavior. These data will be co-variates when we conduct the statistical analysis. **Intervention Names:** - Behavioral: Dietary Intervention **Label:** Interventional **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Interventional **Description:** Participants will be instructed to follow a 16/8 regimen characterized by 16 hours of fasting and an 8-hour eating window daily, on approximately 5 days/week, for 3 months. Previous research has shown that 16 hours of fasting is feasible, safe and well-tolerated among older adults, and that most persons report easy adjustment (Anton, Lee et al. 2019, Lee, Sypniewski et al. 2020). The intervention will be implemented through individual and group sessions with participants and will involve extensive education, coaching, guidance, and support throughout the 3-month intervention. Educational materials on lifestyle factors including physical activity will be provided to each participant. We will be also be collecting data on physical activity and sedentary behavior. These data will be co-variates when we conduct the statistical analysis. **Name:** Dietary Intervention **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** Insulin resistance will be estimated using HOMA-IR. **Measure:** Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) **Time Frame:** Will be assessed at baseline (pre-intervention) and after the 3-month intervention (post-intervention). **Description:** Feasibility will be assessed based on the average number of days per week that participants eat within the 8-hour eating window. The intervention goal is 5 or more days per week. **Measure:** Average number of days per week of time-restricted eating **Time Frame:** The eating window is assessed daily throughout the 3-month intervention. #### Secondary Outcomes **Description:** The Physical Activity and Sedentary Behavior Questionnaire will assess active time and time spent on exercise (PASB-Q; English Version) (Sattler et al., 2020) **Measure:** Physical Activity and Sedentary Behavior Questionnaire Score **Time Frame:** Will be assessed at baseline (pre-intervention) and after the 3-month intervention (post-intervention). **Description:** The Comprehensive Trail Making Test (CTMT) is a measure of organized visual search, attention, set shifting and divided attention (Reynolds 2002). **Measure:** Memory as measured by the Comprehensive TrailMaking Test (CTMT) **Time Frame:** Will be assessed at baseline (pre-intervention) and after the 3-month intervention (post-intervention). **Description:** The Mini Mental State Examination (MMSE) is used extensively in clinical and research settings to systematically measure and assess mental status. It is an 11- question measure that tests five areas of cognitive function: orientation, registration, attention, and calculation, recall, and language (Folstein et al., 1975). **Measure:** Cognitive Impairment as measured by the Mini Mental State Examination (MMSE) **Time Frame:** Will be assessed at baseline (pre-intervention) and after the 3-month intervention (post-intervention). **Description:** The Auditory Verbal Learning Test (AVLT) evaluates verbal memory by presenting a 15- word list five times followed by attempted recall. This is followed by a second 15-word recall interference list, followed by recall of the original list (Rey A. 1964). **Measure:** Verbal Memory as Measured by the Auditory VerbalLearning Test (AVLT) **Time Frame:** Will be assessed at baseline (pre-intervention) and after the 3-month intervention (post-intervention). **Description:** The Digit Span Forward/Backward is a subset of the Wechsler Adult Intelligence Scale (WAIS) that captures attention efficiency and working memory. **Measure:** Working Memory as measured by the WAIS-IV Digit Span Forward/Backward **Time Frame:** Will be assessed at baseline (pre-intervention) and after the 3-month intervention (post-intervention). **Description:** The Comprehensive Assessment of Acceptance and Commitment Therapy Process (CompACT) is a 23 item questionnaire that measures ACT processes, including psychological flexibility (Francis et al., 2016). **Measure:** Psychological Flexibility as Measured by the Comprehensive Assessment of Acceptance and Commitment Therapy Process (CompACT) **Time Frame:** Will be assessed at baseline (pre-intervention) and after the 3-month intervention (post-intervention). **Description:** The Brief Resilience Scale (BRS) has 6 items and is a reliable means of assessing resilience as the ability to bounce back or recover from stress (Smith et al., 2008). **Measure:** Brief Resilience Scale (BRS) Score **Time Frame:** Will be assessed at baseline (pre-intervention) and after the 3-month intervention (post-intervention). **Description:** The Perceived Stress Scale (PSS) is used for measuring the perception of stress. It is a measure of the degree to which situations in one's life are appraised as stressful. The scale also includes questions about current levels of experienced stress (Cohen et al, 1983). **Measure:** Perceived Stress Scale (PSS) Score **Time Frame:** Will be assessed at baseline (pre-intervention) and after the 3-month intervention (post-intervention). **Description:** The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire designed to measure sleep quality and disturbance over past month (Buysse et al.,1989). **Measure:** Pittsburgh Sleep Quality Index (PSQI) Score **Time Frame:** Will be assessed at baseline (pre-intervention) and after the 3-month intervention (post-intervention). **Description:** The WHO QOL has four domains (physical health, psychological, social relationships, and environment). The four domain scores denote an individual's perception of quality of life in each particular domain (WHOQOL Group, 1998). **Measure:** WHO Quality of Life Questionnaire **Time Frame:** Will be assessed at baseline (pre-intervention) and after the 3-month intervention (post-intervention). **Description:** Glycemic control will be assessed by hemoglobin A1c obtained via venipuncture. **Measure:** Hemoglobin A1c **Time Frame:** Will be assessed at baseline (pre-intervention) and after the 3-month intervention (post-intervention) **Description:** Levels of inflammatory biomarkers will be assessed by C-reactive protein obtained via venipuncture. **Measure:** C-reactive protein **Time Frame:** Will be assessed at baseline (pre-intervention) and after the 3-month intervention (post-intervention). **Description:** Study staff will be obtaining a participant blood pressure using an electronic blood pressure cuff. **Measure:** Blood Pressure **Time Frame:** Will be assessed at baseline (pre-intervention) and after the 3-month intervention (post-intervention). ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. aged 60-80 years 2. meet criteria for MCI 3. body mass index \>18.5 and \<40.0 kg/m2 4. access to the internet through computer or smart phone 5. supportive family member (e.g., spouse or adult child) who will help to facilitate study visits and intervention activities 6. education level \> 8 years 7. proficiency in speaking and reading English or having a family member who is proficient in reading and speaking English and is willing to serve as a translator. Exclusion Criteria: 1. diabetes mellitus that requires insulin treatment or is not well managed 2. eating disorder 3. contraindication to time-restricted eating **Healthy Volunteers:** True **Maximum Age:** 80 Years **Minimum Age:** 60 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Yonas E Geda, MD, MSc **Phone:** 833-233-3073 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Geetika Chahal, MBBS **Phone:** 602-406-7240 **Role:** CONTACT #### Locations **Location 1:** **City:** Phoenix **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Susan Racette, Ph.D. - **Phone:** 602-543-1563 - **Role:** CONTACT **Country:** United States **Facility:** Arizona State University, College of Health Solutions **State:** Arizona **Status:** RECRUITING **Zip:** 85004 **Location 2:** **City:** Phoenix **Country:** United States **Facility:** Barrow Neurological Institute, Division of Alzheimer's Disease **State:** Arizona **Status:** ENROLLING_BY_INVITATION **Zip:** 85013 #### Overall Officials **Official 1:** **Affiliation:** Barrow Neurological Institute, Alzheimer's Disease and Cognitive Disorders Division **Name:** Yonas E Geda, MD, MSc **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Description:** The results of this proposed Barrow Neurological Foundation project will provide critical preliminary data for a future large-scale R01 grant application to the National Institutes of Health (NIH), but no individual participant data will be shared. **IPD Sharing:** NO ### References Module #### References **Citation:** Anson RM, Guo Z, de Cabo R, Iyun T, Rios M, Hagepanos A, Ingram DK, Lane MA, Mattson MP. Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake. Proc Natl Acad Sci U S A. 2003 May 13;100(10):6216-20. doi: 10.1073/pnas.1035720100. Epub 2003 Apr 30. **PMID:** 12724520 **Citation:** Anton SD, Lee SA, Donahoo WT, McLaren C, Manini T, Leeuwenburgh C, Pahor M. The Effects of Time Restricted Feeding on Overweight, Older Adults: A Pilot Study. Nutrients. 2019 Jun 30;11(7):1500. doi: 10.3390/nu11071500. **PMID:** 31262054 **Citation:** Anton SD, Moehl K, Donahoo WT, Marosi K, Lee SA, Mainous AG 3rd, Leeuwenburgh C, Mattson MP. Flipping the Metabolic Switch: Understanding and Applying the Health Benefits of Fasting. Obesity (Silver Spring). 2018 Feb;26(2):254-268. doi: 10.1002/oby.22065. Epub 2017 Oct 31. **PMID:** 29086496 **Citation:** Brookmeyer R, Gray S, Kawas C. Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset. Am J Public Health. 1998 Sep;88(9):1337-42. doi: 10.2105/ajph.88.9.1337. **PMID:** 9736873 **Citation:** Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989 May;28(2):193-213. doi: 10.1016/0165-1781(89)90047-4. **PMID:** 2748771 **Citation:** Carlson AJ, Hoelzel F. Apparent prolongation of the life span of rats by intermittent fasting. J Nutr. 1946 Mar;31:363-75. doi: 10.1093/jn/31.3.363. No abstract available. **PMID:** 21021020 **Citation:** Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health Soc Behav. 1983 Dec;24(4):385-96. No abstract available. **PMID:** 6668417 **Citation:** Dimitratos SM, German JB, Schaefer SE. Wearable Technology to Quantify the Nutritional Intake of Adults: Validation Study. JMIR Mhealth Uhealth. 2020 Jul 22;8(7):e16405. doi: 10.2196/16405. **PMID:** 32706729 **Citation:** Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975 Nov;12(3):189-98. doi: 10.1016/0022-3956(75)90026-6. No abstract available. **PMID:** 1202204 **Citation:** Francis, A. W., D. L. Dawson and N. Golijani-Moghaddam (2016). **Citation:** Goodrick CL, Ingram DK, Reynolds MA, Freeman JR, Cider N. Effects of intermittent feeding upon body weight and lifespan in inbred mice: interaction of genotype and age. Mech Ageing Dev. 1990 Jul;55(1):69-87. doi: 10.1016/0047-6374(90)90107-q. **PMID:** 2402168 **Citation:** Goodrick CL, Ingram DK, Reynolds MA, Freeman JR, Cider NL. Differential effects of intermittent feeding and voluntary exercise on body weight and lifespan in adult rats. J Gerontol. 1983 Jan;38(1):36-45. doi: 10.1093/geronj/38.1.36. **PMID:** 6848584 **Citation:** Gudden J, Arias Vasquez A, Bloemendaal M. The Effects of Intermittent Fasting on Brain and Cognitive Function. Nutrients. 2021 Sep 10;13(9):3166. doi: 10.3390/nu13093166. **PMID:** 34579042 **Citation:** Halagappa VK, Guo Z, Pearson M, Matsuoka Y, Cutler RG, Laferla FM, Mattson MP. Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer's disease. Neurobiol Dis. 2007 Apr;26(1):212-20. doi: 10.1016/j.nbd.2006.12.019. Epub 2007 Jan 13. **PMID:** 17306982 **Citation:** HARMAN D. Aging: a theory based on free radical and radiation chemistry. J Gerontol. 1956 Jul;11(3):298-300. doi: 10.1093/geronj/11.3.298. No abstract available. **PMID:** 13332224 **Citation:** Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, Holtzman DM, Jagust W, Jessen F, Karlawish J, Liu E, Molinuevo JL, Montine T, Phelps C, Rankin KP, Rowe CC, Scheltens P, Siemers E, Snyder HM, Sperling R; Contributors. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018 Apr;14(4):535-562. doi: 10.1016/j.jalz.2018.02.018. **PMID:** 29653606 **Citation:** Lee SA, Sypniewski C, Bensadon BA, McLaren C, Donahoo WT, Sibille KT, Anton S. Determinants of Adherence in Time-Restricted Feeding in Older Adults: Lessons from a Pilot Study. Nutrients. 2020 Mar 24;12(3):874. doi: 10.3390/nu12030874. **PMID:** 32213965 **Citation:** Martens CR, Rossman MJ, Mazzo MR, Jankowski LR, Nagy EE, Denman BA, Richey JJ, Johnson SA, Ziemba BP, Wang Y, Peterson CM, Chonchol M, Seals DR. Short-term time-restricted feeding is safe and feasible in non-obese healthy midlife and older adults. Geroscience. 2020 Apr;42(2):667-686. doi: 10.1007/s11357-020-00156-6. Epub 2020 Jan 23. **PMID:** 31975053 **Citation:** Mattson MP, Moehl K, Ghena N, Schmaedick M, Cheng A. Intermittent metabolic switching, neuroplasticity and brain health. Nat Rev Neurosci. 2018 Feb;19(2):63-80. doi: 10.1038/nrn.2017.156. Epub 2018 Jan 11. Erratum In: Nat Rev Neurosci. 2020 Aug;21(8):445. **PMID:** 29321682 **Citation:** McCay CM, Crowell MF, Maynard LA. The effect of retarded growth upon the length of life span and upon the ultimate body size. 1935. Nutrition. 1989 May-Jun;5(3):155-71; discussion 172. No abstract available. **PMID:** 2520283 **Citation:** Mitchell SJ, Bernier M, Mattison JA, Aon MA, Kaiser TA, Anson RM, Ikeno Y, Anderson RM, Ingram DK, de Cabo R. Daily Fasting Improves Health and Survival in Male Mice Independent of Diet Composition and Calories. Cell Metab. 2019 Jan 8;29(1):221-228.e3. doi: 10.1016/j.cmet.2018.08.011. Epub 2018 Sep 6. **PMID:** 30197301 **Citation:** Ooi TC, Meramat A, Rajab NF, Shahar S, Ismail IS, Azam AA, Sharif R. Intermittent Fasting Enhanced the Cognitive Function in Older Adults with Mild Cognitive Impairment by Inducing Biochemical and Metabolic changes: A 3-Year Progressive Study. Nutrients. 2020 Aug 30;12(9):2644. doi: 10.3390/nu12092644. **PMID:** 32872655 **Citation:** Ooi TC, Meramat A, Rajab NF, Shahar S, Sharif R. Antioxidant Potential, DNA Damage, Inflammation, Glycemic Control and Lipid Metabolism Alteration: A Mediation Analysis of Islamic Sunnah Intermittent Fasting on Cognitive Function among Older Adults with Mild Cognitive Impairment. J Nutr Health Aging. 2022;26(3):272-281. doi: 10.1007/s12603-022-1757-0. **PMID:** 35297471 **Citation:** Reiman EM, Caselli RJ, Yun LS, Chen K, Bandy D, Minoshima S, Thibodeau SN, Osborne D. Preclinical evidence of Alzheimer's disease in persons homozygous for the epsilon 4 allele for apolipoprotein E. N Engl J Med. 1996 Mar 21;334(12):752-8. doi: 10.1056/NEJM199603213341202. **PMID:** 8592548 **Citation:** Rey, A. (1964). L'examen clinique en psychologie. Paris, Presses Universitaires de France. **Citation:** Reynolds, C. R. (2002). Comprehensive trail-making test : examiner's manual. Austin, Tex., Pro-Ed. **Citation:** Roy M, Rheault F, Croteau E, Castellano CA, Fortier M, St-Pierre V, Houde JC, Turcotte EE, Bocti C, Fulop T, Cunnane SC, Descoteaux M. Fascicle- and Glucose-Specific Deterioration in White Matter Energy Supply in Alzheimer's Disease. J Alzheimers Dis. 2020;76(3):863-881. doi: 10.3233/JAD-200213. **PMID:** 32568202 **Citation:** Rubinsztein DC, Frake RA. Yoshinori Ohsumi's Nobel Prize for mechanisms of autophagy: from basic yeast biology to therapeutic potential. J R Coll Physicians Edinb. 2016 Dec;46(4):228-233. doi: 10.4997/jrcpe.2016.403. **PMID:** 28504774 **Citation:** Sattler MC, Jaunig J, Tosch C, Watson ED, Mokkink LB, Dietz P, van Poppel MNM. Current Evidence of Measurement Properties of Physical Activity Questionnaires for Older Adults: An Updated Systematic Review. Sports Med. 2020 Jul;50(7):1271-1315. doi: 10.1007/s40279-020-01268-x. **PMID:** 32125670 **Citation:** Smith BW, Dalen J, Wiggins K, Tooley E, Christopher P, Bernard J. The brief resilience scale: assessing the ability to bounce back. Int J Behav Med. 2008;15(3):194-200. doi: 10.1080/10705500802222972. **PMID:** 18696313 **Citation:** Sutton EF, Beyl R, Early KS, Cefalu WT, Ravussin E, Peterson CM. Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes. Cell Metab. 2018 Jun 5;27(6):1212-1221.e3. doi: 10.1016/j.cmet.2018.04.010. Epub 2018 May 10. **PMID:** 29754952 **Citation:** Wechsler, D. (1997). Wechsler Adult Intelligence Scale-III. New York, The Psychological Corporation. **Citation:** Weindruch R. The retardation of aging by caloric restriction: studies in rodents and primates. Toxicol Pathol. 1996 Nov-Dec;24(6):742-5. doi: 10.1177/019262339602400618. **PMID:** 8994305 **Citation:** Development of the World Health Organization WHOQOL-BREF quality of life assessment. The WHOQOL Group. Psychol Med. 1998 May;28(3):551-8. doi: 10.1017/s0033291798006667. **PMID:** 9626712 **Citation:** Wilson, K. G., Sandoz, E. K., Kitchens, J., & Roberts, M. E. (2010). ## Derived Section ### Condition Browse Module - Ancestors - ID: D000003704 - Term: Dementia - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000024801 - Term: Tauopathies - ID: D000019636 - Term: Neurodegenerative Diseases - ID: D000019965 - Term: Neurocognitive Disorders - ID: D000001523 - Term: Mental Disorders ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M3885 - Name: Alzheimer Disease - Relevance: HIGH - As Found: Alzheimer's Disease - ID: M29705 - Name: Cognitive Dysfunction - Relevance: LOW - As Found: Unknown - ID: M6904 - Name: Dementia - Relevance: LOW - As Found: Unknown - ID: M5204 - Name: Brain Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M23002 - Name: Tauopathies - Relevance: LOW - As Found: Unknown - ID: M21558 - Name: Neurodegenerative Diseases - Relevance: LOW - As Found: Unknown - ID: M21836 - Name: Neurocognitive Disorders - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown - ID: T2192 - Name: Familial Alzheimer Disease - Relevance: HIGH - As Found: Alzheimer's Disease ### Condition Browse Module - Meshes - ID: D000000544 - Term: Alzheimer Disease ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429111 **Brief Title:** Effectiveness and Safety in Maternal and Neonatal Outcomes in Water Birth. **Official Title:** Effectiveness and Safety in Maternal and Neonatal Outcomes of Waterbirth Compared to Delivery in Women Using Epidural Analgesia #### Organization Study ID Info **ID:** water birth #### Organization **Class:** OTHER **Full Name:** Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana ### Status Module #### Completion Date **Date:** 2023-03-24 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2023-02-24 **Type:** ACTUAL #### Start Date **Date:** 2020-06-06 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Study First Submit Date:** 2024-05-15 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Universitat Jaume I **Class:** OTHER **Name:** Hospital Universitario de la Plana #### Lead Sponsor **Class:** OTHER **Name:** Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana #### Responsible Party **Investigator Affiliation:** Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana **Investigator Full Name:** Soledad Carregui Villar **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Childbirth is a unique and non-transferable experience in the life of a woman, her partner and her family. It is a very intense process that requires accompaniment and, in the vast majority of cases, requires analgesic support in order to overcome this life event in an optimal and atraumatic way. Among the analgesic methods for pain relief during the labor process, there are pharmacological and non-pharmacological methods. From the evidence we know that the most effective pharmacological method is epidural analgesia (EA), while the most recognized non-pharmacological method is immersion in hot water (bathtub) for dilatation and delivery, called waterbirth(WB) At present there is controversy and doubts about the increase in the number of interventions involving the use of epidural analgesia, but there is also controversy about the safety of the use of water, especially in those processes where the birth ends in water. Given the popularity of these two methods, the aim is to study and compare the maternal and neonatal outcomes derived from the use of both methods in order to provide greater knowledge to women in their decision making. **Detailed Description:** At present there is controversy and doubts about the increase in the number of interventions involving the use of epidural analgesia(EA), but there is also controversy about the safety of the use of water, especially in those processes where the birth ends in water, called Waterbirth (WB). Given the popularity of these two methods, the aim is to study and compare the maternal and neonatal outcomes derived from the use of both methods in order to provide greater knowledge to women in their decision making. For this purpose, a prospective observational study will be carried out in low-risk pregnant women (who do not present any complication at the time of delivery) who freely choose one or the other method at the beginning of their labor process. For this reason, the socio-demographic characteristics, the obstetric interventions carried out during the process, the results, the possible maternal and neonatal complications, aspects of breastfeeding, as well as the evaluation of the degree of satisfaction will be described and compared between the two groups. The study was carried out at the Hospital Universitario La Plana, a referral center for normal childbirth, where the healthcare team has experience in the management of both methods. After obtaining the approval of the ethics committee (CEI), recruitment of the cases began and was carried out between June 2020 and February 2023. Overall, 642 cases were recruited, distributed in a total of 359 women who chose water immersion, of whom 40 women subsequently opted for epidural analgesia and 283 women who chose epidural analgesia initially. Women who completed the water birth totaled 263 cases. The data concerning clinical variables were extracted from the electronic clinical records of the medical history of both the mother and the neonate and subsequently transcribed into a web portal designed to facilitate the transcription of the multiple variables. The final database is exploited from this web portal in Excel format and exported to the Statistical Package for Social Sciences (SPPSS) program version for subsequent analysis. The variables collected for subsequent analysis are classified into sociodemographic variables, maternal clinical variables, neonatal clinical variables and satisfaction variables. Satisfaction will be measured according to the Women's Satisfaction with Childbirth Experience Scale. Translated and validated version of the Mackey Satisfaction Childbirth Rating Scale. This scale, originally developed in English, measures women's satisfaction with the experience of childbirth and childbirth. It is a self-completed questionnaire, which is administered to the woman before discharge from the hospital. It consists of 34 items grouped into five subscales referring to the woman (9 items), the partner (2 items), the newborn (3 items), the midwife (9 items) and the obstetrician (8 items). It also contains a subscale for overall assessment of the experience (3 items). Each item is evaluated on a 5-point Likert scale ranging from very dissatisfied (1) to very satisfied (5), with a neutral central value. The final score of the scale is obtained by adding the values assigned to each item, so that the higher the score, the greater the satisfaction. Similarly, partial scores can be obtained for each subscale. In our study, the obstetrician dimension was eliminated since in women in the waterbirth group the care offered during the process is carried out by the midwife and the women do not receive assistance from the physician. OBJECTIVES The General Objective of the study is to compare the effectiveness and safety of the use of water during dilatation and delivery versus the administration of epidural analgesia in low-risk women. The Specific Objectives are: . To describe and compare between the two groups the socio-demographic and obstetric characteristics of the pregnant women participating in the study (age, parity, weeks of gestation, type of breastfeeding chosen, level of education, country of origin, vagino-rectal colonization by beta-hemolytic streptococcus, weight of the NB, sex). To describe and compare between the two groups the difference in obstetric interventions (administration of oxytocin, amniorrhexis, bladder catheterization, fetal calcium levels, need for other analgesic support during the process, episiotomy and position adopted by the mother for the birth). * To describe and compare between both groups the maternal outcomes of the process (end of labor, dilatation time, expulsion time, perineal tears, duration of admission, visits to the emergency department during the first month of life). * To describe and compare between both groups the possible maternal complications that occur in the process (instrumental delivery, cesarean section, Fetal Healt rate(FHR),alterations, III and IV degree tear, presence of obstetric emergency, intrapartum fever and puerperal infection). * To describe and compare between both groups the neonatal outcomes (Apgar of the newborn at one minute, 5 and 10 minutes, cord arterial pH, venous arterial pH, base excess, need for neonatal ventilation support, admission to the neonatal unit or Neonatal Intensive care unit (NICU), reason and duration of admission). * To describe and compare between both groups the initiation and evolution of breastfeeding (initial choice, breastfeeding at discharge, neonatal alertness at birth, type of latch, supplementation during hospital stay). * To describe and compare between the two groups the degree of satisfaction with childbirth between the epidural and water use groups according to the validated Mackey Scale, assessing the dimensions of woman, partner, newborn, midwife and overall assessment of the experience. TREATMENT OF SUBJECTS - SAMPLING TECHNIQUE The non-probabilistic consecutive sampling technique will be used, offering the study to women who meet the inclusion criteria and have no exclusion criteria. The women will be recruited in the Delivery Service when the pregnant woman finishes the delivery process, while still in the dilation room, and who meet the inclusion criteria and have no exclusion criteria. After the information, the patient will be offered an information sheet and the informed consent form to be signed before leaving the delivery room. The variable recorded in the form of the labor dilatation sheet of the mother's medical history that defines whether the woman is low risk at the time of delivery will be taken into account, this characteristic is defined in the partogram and is a mandatory field that is filled in by the professional to the question "candidate use of water" YES/NO to alert the researcher about the possible case to be considered in the study, this response is conditioned by the protocol for the use of water available at the Hospital de La Plana (the characteristics that indicate whether or not the use of water in childbirth is indicated are clearly defined). After delivery, the midwife will offer the woman the possibility of entering the study, offering her the information sheet and the informed consent form that she will have to sign before discharge from the hospital. In the event that the consent and information is not offered in the delivery service for any reason, it can be done later as long as it is before discharge from the hospital. Entry into the study will not influence routine clinical practice, since it does not involve any action on the subjects under study. The intervention will be in the analysis of the variables to be studied, this implies the consent of the woman for the exploitation of the data from her Electronic Medical Record and that of her newborn through the forms that are usually used in all childbirth processes. On the other hand, it is necessary to fill in a satisfaction questionnaire, which will be given by the midwife before the woman leaves the delivery service. This questionnaire can be completed from the postpartum period until the woman is discharged from the hospital, and will be collected by the midwife who visits the hospital ward during the days that the woman remains hospitalized, before discharge. . Before starting the study, a meeting will be held to review the protocol, the data collection booklet and the guidelines to be followed by the personnel involved in the study. The researcher is committed to compliance with the Organic Law 3/2018, of December 5, on Personal Data Protection (LOPD) and guarantee of digital rights, published in the Boletin Oficial del Estado (BOE), as wel as Regulation (EU) 2016/679 of the European Parliament. The data collected for the study will be pseudonymized, so that it does not include information that can identify patients. In accordance with Law 41/2002, of November 14, 2002, basic law regulating patient autonomy and rights and obligations regarding information and clinical documentation, all potential candidates will be given an informative document of the study and informed consent so that they can make a rational, free decision in accordance with their values and preferences. No patient can be included in the study without prior informed consent. The investigator consents, when signing the protocol, to adhere to the instructions and procedures described in them and thus follow the principles of good clinical practice that they imply. The investigator submitted the relevant documentation to the Research and Ethics Committee (CEI). The study was not initiated until CEI approval was obtained. Similarly, the managers and the management team were informed for their express consent. The safety of the study will be controlled through the delivery staff of the Hospital Universitario La Plana, since this study not modify the usual clinical practice by not performing any intervention required by the study in any of the groups. In the design of the study, priority is given to not randomizing the sample, since ethically, the woman's ability to choose and the fulfillment of her expectations regarding childbirth are prioritized. The researcher attaches a declaration of absence of conflict of interest. This study will be carried out according to the Standards of Good Clinical Practice and in accordance with the Declaration of Helsinki 1975, amended in 1983. Patients' names and initials will not be included. DATA MANAGEMENT AND ARCHIVING OF RECORDS The data necessary for carrying out the study will be collected from the Pregnancy Chart, which classifies whether the pregnant woman has any risk factors, from the hospital medical record entered in the Conficita program of the Hospital Universitario La Plana, where we will access the Obstetric Admission Sheet, the Dilatation-Delivery Sheet, the Newborn Sheet and the Neonatal Follow-Up Sheet in order to collect the variables described in the study. These variables will be collected in a Data Collection Notebook (Annex II). Subsequently, these data will be collected in the SPSS database and stored in a Clinical Research File (FIC), included in the FIC of the research project of the Department of Health of the Hospital La Pana, attached to the FIC whose owner is the Conselleria de Sanitat. Only the researchers will have access to these data; their sole purpose will be to carry out the present study and the data analysis will be performed with the help of the SPSS statistical package for Windows. On the occasion of the study, a file will be generated with all the documentation of the study, which will be kept by the researcher. The study documentation will be kept for the time required by current legislation, after which it will be destroyed according to the rules of the service on destruction of documents with personal information. The investigator allows direct access to the data or source documents for monitoring, auditing and review by the IRB. The study may be audited by the Health Authorities during the study or even when the study is completed, to assess compliance with Good Clinical Practice guidelines. No data revealing the identity of the patients should leave the center. PUBLICATION POLICY The results of the study will be the property of the investigator who will establish the publication policy. In addition, the anonymity of the patients participating in the study will be guaranteed at all times. This work is a doctoral thesis of the Biomedical Sciences program of the Universitat Jaume I of Castellón, tutored by Dr. Eladio Collado Boira, Dr. Eva Moya Artuñedo and Dr. Ricardo Tosca Segura. ### Conditions Module **Conditions:** - Natural Childbirth - Water Birth - Neonatal Asphyxia - Outcome, Adverse Birth - Labor Pain - Obstetric Pain ### Design Module #### Design Info **Observational Model:** CASE_CONTROL **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 642 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** * Pregnant women at term with normal pregnancy without the presence of maternal and neonatal risk factors who meet criteria according to the protocol for the use of water and who choose epidural analgesia at the time of admission to the dilatation room in active labor. * Over 17 years of age * Psychic and cognitive capacity for decision making * Willingness to take part in the study and signature of the informed consent form. * Absence of ideomatic barrier **Intervention Names:** - Procedure: Epidural analgesia **Label:** low-risk pregnant women who freely chooses to use epidural analgesia during labor #### Arm Group 2 **Description:** Pregnant women at term with normal pregnancy without the presence of maternal and neonatal risk factors who meet criteria according to the protocol for the use of water and who choose immersion water at the time of admission to the dilatation room in active labor. * Over 17 years of age * Psychic and cognitive capacity for decision making * Willingness to take part in the study and signature of the informed consent form. * Absence of ideomatic barrier **Intervention Names:** - Procedure: Immersion water **Label:** low-risk pregnant woman who freely chooses the use of water during childbirt ### Interventions #### Intervention 1 **Arm Group Labels:** - low-risk pregnant women who freely chooses to use epidural analgesia during labor **Description:** Consists of a central nerve block by injecting a local anesthetic near the nerves that transmit pain, in the lumbar region, for pain relief during labor. **Name:** Epidural analgesia **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - low-risk pregnant woman who freely chooses the use of water during childbirt **Description:** Consists of the use of hot water immersion in a birthing tub during labor and/or delivery. **Name:** Immersion water **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** How labor is terminated : Normal in water Normal underwater Instrumented delivery Cesarean section **Measure:** Completion of labor **Time Frame:** 24 hours **Description:** Yes/no intrapartum oxytocin required **Measure:** intrapartum administration of oxytocin **Time Frame:** 24 hours **Description:** If intrapartum amniotomy is needed YES/NO **Measure:** Amniotomy **Time Frame:** 24 hours **Description:** Frequency of non-reassuring or pathological episodes in the cardiotocographic recording. (Scale) **Measure:** presence of fetal heart rate abnormalities Frequency of non-reassuring or pathological episodes in the cardiotocographic recording. **Time Frame:** 24 hours **Description:** Number of times bladder catheterization is performed during the delivery process (Scale) **Measure:** Number of bladder catheterizations **Time Frame:** Up to 24 hours **Description:** Determination of pH and lactate from fetal scalp blood to study the management of intrapartum fetal hypoxia. Only when when there is suspicion of risk of loss of fetal well-being due to a non-reassuring or pathological cardiotocographic monitor. (Scale) **Measure:** Number of scalp blood determinations **Time Frame:** Up to 24 hours **Description:** Presence of intrapartum fever YES/NO **Measure:** Intrapartum fever **Time Frame:** Up tu 24 hours **Description:** An obstetric emergency is considered to be the occurrence of any episode of: Cord rupture puerperal hemorrhage Shoulder impaction Manual removal of placenta Risk of loss of fetal well-being (Nominal) **Measure:** Presence of obstetric emergency **Time Frame:** Up to 24 hours **Description:** Injury to the genital tract due to spontaneous trauma as a result of childbirth. These traumas are classified according to Sultan 1999 according to the injury produced: First degree: Injury to the perineal skin and mucosa. Second degree: Injury to perineal muscles without affecting the anal sphincter. Third degree a.- Injury that reaches the external anal sphincter affecting less than 50%. Third degree b.- Injury reaching the external anal sphincter affecting more than 50%. Third degree c.- Injury reaching the complete external anal sphincter and internal anal sphincter. Fourth degree: Injury to the external anal sphincter plus the internal anal sphincter plus the anal epithelium. (Nominal) **Measure:** Perineal tear **Time Frame:** Up to 24 hours **Description:** A one-minute assessment of five items that determine a numerical value called the "Apgar test" that evaluates cardiac activity, respiratory effort, reflexes, muscle tone and skin color. If the value is less than or equal to 7, it is interpreted as a poor neonatal adaptation; if it is greater than 7, it is interpreted as an adequate adaptation. (Scale) **Measure:** Apgar score at one minuto of life of the neonate. **Time Frame:** Up to 24 hours **Description:** A five minutes assessment of five items that determine a numerical value called the "Apgar test" that evaluates cardiac activity, respiratory effort, reflexes, muscle tone and skin color. If the value is less than or equal to 7, it is interpreted as a poor neonatal adaptation; if it is greater than 7, it is interpreted as an adequate adaptation. (Scale) **Measure:** Apgar score at five minuts of life of the neonate. **Time Frame:** Up to 24 hours **Description:** Value determining the analysis of blood samples from the umbilical cord artery after birth. The purpose of this analysis is to determine the degree of possible fetal hypoxia suffered by the newborn during delivery. The blood sample will be taken without clamping the umbilical cord in the case of late cord. A value lower than 7.10 can be interpreted as a higher risk of fetal hypoxia. (Scale) **Measure:** Arterial cord blood ph **Time Frame:** Up to 24 hours **Description:** If the neonate requires after birth support with positive ventilation, oxygen administration or intubation. YES/NO **Measure:** Neonatal ventilation support **Time Frame:** Up to 24 hours **Description:** Presence of respiratory distress in the neonate during the first two hours of life. YES/NO **Measure:** Presence of distress neonatal **Time Frame:** Up to 48 hours **Description:** Describes if the neonate needs to be admitted to the neonatal unit. YES/NO **Measure:** Neonatal admission **Time Frame:** Up to 30 days **Description:** Describes whether neonatal sepsis has occurred.YES/NO **Measure:** Neonatal sepsis **Time Frame:** Up to 30 days **Description:** Describes whether the neonate has a diagnosis of hypoxic ischemic encephalopathy. **Measure:** Presence of hypoxic ischemic encephalopathy **Time Frame:** 1 month **Description:** Presence of any type of maternal infection in the postpartum period (urinary tract infection, endometritis, mastitis or others), YES/NO **Measure:** Maternal infection **Time Frame:** Up to 1 month **Description:** Type of breastfeeding established at hospital discharge: Breastfeeding Artificial breastfeeding Mixed breastfeeding **Measure:** Breastfeeding upon hospital discharge **Time Frame:** Up to 1 week **Description:** Number of urgent hospital visits made by the woman during the first postpartum month. (Scale) **Measure:** Visits to the hospital emergency department during the first month postpartum **Time Frame:** Up to1 month **Description:** Measured according to the validation of the Mackey Childbirth Satisfaction Rating Scale. It consists of 34 items grouped in five subscales referring to the woman (9 items), the partner (2 items), the newborn (3 items), the midwife (9 items) and the obstetrician (8 items). It also contains a subscale for overall assessment of the experience (3 items). Each item is evaluated on a 5-point Likert scale ranging from very dissatisfied (1) to very satisfied (5), with a neutral central value. The final score of the scale is obtained by adding the values assigned to each item, so that the higher the score, the greater the satisfaction. Similarly, partial scores can be obtained for each subscale. The questionnaire is offered to the woman in the postpartum period and is collected before discharge from the hospital. **Measure:** Maternal satisfaction **Time Frame:** Up to 3 days #### Secondary Outcomes **Description:** cervical dilatation in centimeters at the time of analgesic method choice **Measure:** cervical dilatation at the time of choice of analgesic method **Time Frame:** Up to 24 hours **Description:** vagino-rectal colonization with positive result for group B streptococcus at the time of delivery **Measure:** group b streptococcus colonization during gestation **Time Frame:** Up to 24 hours **Description:** Duration in minutes of the dilation phase from admission to the delivery room until the beginning of the active expulsion period (Scale) **Measure:** Duration of the dilatation phase **Time Frame:** Up to 24 hours **Description:** Duration in minutes of the active phase of the second stage of labor from the start of pushing to delivery. **Measure:** Duration of the active second stage of labor **Time Frame:** Up to 24 hours **Description:** Type of pushes performed by the woman during the second stage of labor. They can be directed pushes or spontaneous pushes. **Measure:** Type of expulsion **Time Frame:** Up to 24 hours **Description:** Management of third stage of labor: * Active if oxytocin and directed labor are used * Passive -physiologic management **Measure:** Management of the third stage of labor **Time Frame:** Up to 24 hours **Description:** newborn birth weight expressed in grams **Measure:** newborn birth weight **Time Frame:** Up to 24 hours **Description:** sex of the newborn * male * female **Measure:** sex of the newborn **Time Frame:** Up to 24 hours **Description:** Breastfeeding chosen after birth * Breastfeeding * Artificial feeding **Measure:** Breastfeeding chosen after birth **Time Frame:** Up to 24 hours **Description:** * Spontaneous onset * Spontaneous onset * Onset with maternal support * Onset with professional help * No initiation **Measure:** Type of latch-on of the baby at the onset of breastfeeding during the first two hours postpartum **Time Frame:** Up to 48 hours **Description:** * Infectious risk * Glycemic control * Jaundice * Feeding problems * Fetal malformations * Distress * Neonatal Sepsis * Transfer to neonatal ICU * Other * No admission **Measure:** Reason for admission **Time Frame:** Up to 1 month **Description:** Number of times the baby is offered supplementation with formula during hospital stay (Scale) **Measure:** Supplementation during hospital stay **Time Frame:** At the time of hospital discharge **Description:** Days the newborn stays in the hospital **Measure:** Length of stay in days **Time Frame:** At the time of hospital discharge ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Pregnant women at term with normal pregnancy without the presence of maternal and neonatal risk factors that preclude the use of water and epidural analgesia at the time of admission to the delivery room. Pregnant women who are 18 years of age or older or who will turn 18 in the year of delivery. * Have the psychic and cognitive capacity to make decisions. * Desire to be part of the study and signature of informed consent to participate in the study. Exclusion Criteria: * .Presence of any maternal or fetal risk factor that precludes the choice of water or epidural analgesia at the time of admission to the dilation room in active labor. Under 17 years of age or under 18 years of age in the year of delivery. .Ideomatic barrier that makes it impossible for the patient to understand the study and to agree to the informed consent, .Unwillingness to participate or failure to sign the informed consent form. **Maximum Age:** 46 Years **Minimum Age:** 17 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** FEMALE **Standard Ages:** - CHILD - ADULT **Study Population:** The Hospital Universitario La Plana is the reference center of the Health Department No. 3, is a regional hospital located in the city of Vila-real, province of Castellon. Candidates for participation in the study are full-term pregnant women who meet the inclusion criteria and who are admitted to the dilation room during the active labor period in the Delivery Service of the Hospital Universitario La Plana during the period from April 2020 to June 2023. ### Contacts Locations Module #### Locations **Location 1:** **City:** Vila-real **Country:** Spain **Facility:** Hospital Universitario La Plana **State:** Castellon **Zip:** 12540 #### Overall Officials **Official 1:** **Affiliation:** Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana **Name:** Soledad Carregui Vilar, Midwife **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Description:** We plan to publish the data available to other researchers, including the study protocol, the protocol for water use at la plana university hospital and the informed consent form. **IPD Sharing:** UNDECIDED ### References Module #### References **Citation:** Cluett ER, Burns E, Cuthbert A. Immersion in water during labour and birth. Cochrane Database Syst Rev. 2018 May 16;5(5):CD000111. doi: 10.1002/14651858.CD000111.pub4. **PMID:** 29768662 **Citation:** Anim-Somuah M, Smyth RM, Cyna AM, Cuthbert A. Epidural versus non-epidural or no analgesia for pain management in labour. Cochrane Database Syst Rev. 2018 May 21;5(5):CD000331. doi: 10.1002/14651858.CD000331.pub4. **PMID:** 29781504 **Citation:** Shaw-Battista J. Systematic Review of Hydrotherapy Research: Does a Warm Bath in Labor Promote Normal Physiologic Childbirth? J Perinat Neonatal Nurs. 2017 Oct/Dec;31(4):303-316. doi: 10.1097/JPN.0000000000000260. **PMID:** 28520654 **Citation:** Lewis L, Hauck YL, Butt J, Hornbuckle J. Obstetric and neonatal outcomes for women intending to use immersion in water for labour and birth in Western Australia (2015-2016): A retrospective audit of clinical outcomes. Aust N Z J Obstet Gynaecol. 2018 Oct;58(5):539-547. doi: 10.1111/ajo.12758. Epub 2018 Jan 17. **PMID:** 29344940 **Citation:** Bovbjerg ML, Cheyney M, Caughey AB. Maternal and neonatal outcomes following waterbirth: a cohort study of 17 530 waterbirths and 17 530 propensity score-matched land births. BJOG. 2022 May;129(6):950-958. doi: 10.1111/1471-0528.17009. Epub 2021 Dec 1. **PMID:** 34773367 **Citation:** Liu Y, Liu Y, Huang X, Du C, Peng J, Huang P, Zhang J. A comparison of maternal and neonatal outcomes between water immersion during labor and conventional labor and delivery. BMC Pregnancy Childbirth. 2014 May 6;14:160. doi: 10.1186/1471-2393-14-160. **PMID:** 24886438 **Citation:** Yu M, Qian H, Gan M. Comparison of different interventions for the reduction of labor pain: A systematic review and network meta-analysis. Medicine (Baltimore). 2024 Mar 8;103(10):e37047. doi: 10.1097/MD.0000000000037047. **PMID:** 38457589 **Citation:** McKinney JA, Vilchez G, Jowers A, Atchoo A, Lin L, Kaunitz AM, Lewis KE, Sanchez-Ramos L. Water birth: a systematic review and meta-analysis of maternal and neonatal outcomes. Am J Obstet Gynecol. 2024 Mar;230(3S):S961-S979.e33. doi: 10.1016/j.ajog.2023.08.034. Epub 2024 Jan 9. **PMID:** 38462266 **Citation:** Seed E, Kearney L, Weaver E, Ryan EG, Nugent R. A prospective cohort study comparing neonatal outcomes of waterbirth and land birth in an Australian tertiary maternity unit. Aust N Z J Obstet Gynaecol. 2023 Feb;63(1):59-65. doi: 10.1111/ajo.13555. Epub 2022 Jul 7. **PMID:** 35796252 **Citation:** Zhang G, Yang Q. Comparative Efficacy of Water and Conventional Delivery during Labour: A Systematic Review and Meta-Analysis. J Healthc Eng. 2022 Mar 29;2022:7429207. doi: 10.1155/2022/7429207. eCollection 2022. **PMID:** 35392147 **Citation:** Ulfsdottir H, Saltvedt S, Edqvist M, Georgsson S. Management of the active second stage of labor in waterbirths compared with conventional births - a prospective cohort study. Midwifery. 2022 Apr;107:103283. doi: 10.1016/j.midw.2022.103283. Epub 2022 Feb 8. **PMID:** 35172265 **Citation:** Reviriego-Rodrigo E, Ibargoyen-Roteta N, Carregui-Vilar S, Mediavilla-Serrano L, Uceira-Rey S, Iglesias-Casas S, Martin-Casado A, Toledo-Chavarri A, Ares-Mateos G, Montero-Carcaboso S, Castello-Zamora B, Burgos-Alonso N, Moreno-Rodriguez A, Hernandez-Tejada N, Koetsenruyter C. Experiences of water immersion during childbirth: a qualitative thematic synthesis. BMC Pregnancy Childbirth. 2023 May 29;23(1):395. doi: 10.1186/s12884-023-05690-7. **PMID:** 37248449 **Citation:** Burns E, Feeley C, Hall PJ, Vanderlaan J. Systematic review and meta-analysis to examine intrapartum interventions, and maternal and neonatal outcomes following immersion in water during labour and waterbirth. BMJ Open. 2022 Jul 5;12(7):e056517. doi: 10.1136/bmjopen-2021-056517. Erratum In: BMJ Open. 2022 Sep 27;12(9):e056517corr1. **PMID:** 35790327 **Citation:** Vanderlaan J, Hall P. Systematic Review of Case Reports of Poor Neonatal Outcomes With Water Immersion During Labor and Birth. J Perinat Neonatal Nurs. 2020 Oct/Dec;34(4):311-323. doi: 10.1097/JPN.0000000000000515. **PMID:** 33079805 **Citation:** Ulfsdottir H, Saltvedt S, Georgsson S. Women's experiences of waterbirth compared with conventional uncomplicated births. Midwifery. 2019 Dec;79:102547. doi: 10.1016/j.midw.2019.102547. Epub 2019 Sep 30. **PMID:** 31610362 **Citation:** Committee Opinion No. 679 Summary: Immersion in Water During Labor and Delivery. Obstet Gynecol. 2016 Nov;128(5):1198-1199. doi: 10.1097/AOG.0000000000001765. **PMID:** 27776069 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010146 - Term: Pain - ID: D000009461 - Term: Neurologic Manifestations - ID: D000003643 - Term: Death - ID: D000010335 - Term: Pathologic Processes - ID: D000014947 - Term: Wounds and Injuries - ID: D000007232 - Term: Infant, Newborn, Diseases - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M26008 - Name: Labor Pain - Relevance: HIGH - As Found: Labor Pain - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M4545 - Name: Asphyxia Neonatorum - Relevance: HIGH - As Found: Neonatal Asphyxia - ID: M4544 - Name: Asphyxia - Relevance: HIGH - As Found: Asphyxia - ID: M14127 - Name: Pregnancy Complications - Relevance: HIGH - As Found: Outcome, Adverse Birth - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: M6845 - Name: Death - Relevance: LOW - As Found: Unknown - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown - ID: M10276 - Name: Infant, Newborn, Diseases - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: T513 - Name: Asphyxia Neonatorum - Relevance: HIGH - As Found: Neonatal Asphyxia ### Condition Browse Module - Meshes - ID: D000011248 - Term: Pregnancy Complications - ID: D000001238 - Term: Asphyxia Neonatorum - ID: D000048949 - Term: Labor Pain - ID: D000001237 - Term: Asphyxia ### Intervention Browse Module - Browse Branches - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M4107 - Name: Anesthetics - Relevance: LOW - As Found: Unknown - ID: M4109 - Name: Anesthetics, Local - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429098 **Brief Title:** Study of A Venetoclax-based, Anthracycline-free Regimen in Newly Diagnosed CBFβ::MYH11(+) AML **Official Title:** Study of A Venetoclax-based, Anthracycline-free Regimen in Patients With Newly Diagnosed CBFβ::MYH11-positive Acute Myeloid Leukemia #### Organization Study ID Info **ID:** 2023371 #### Organization **Class:** OTHER **Full Name:** The First Affiliated Hospital of Soochow University ### Status Module #### Completion Date **Date:** 2027-12-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2027-06-30 **Type:** ESTIMATED #### Start Date **Date:** 2024-01-01 **Type:** ACTUAL **Status Verified Date:** 2023-12 #### Study First Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Study First Submit Date:** 2024-05-14 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** The First Affiliated Hospital of Soochow University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** This investigator-initiated, single-arm, phase II trial is aimed to evaluate the efficacy and safety of a venetoclax-based, anthracycline-free regimen in patients with newly diagnosed CBFβ::MYH11-positive acute myeloid leukemia. **Detailed Description:** Primary Objectives: To determine the CR (complete remission) / CRi (complete remission with incomplete blood count recovery) rate of 2 cycles of VEN/HMA in patients with newly diagnosed (ND) CBFβ::MYH11-positive acute myeloid leukemia(AML). Secondary Objectives: 1. To determine the overall response rate (ORR) of 2 cycles of VEN/HMA in patients with ND CBFβ::MYH11-positive AML. 2. To determine the safety of the combination regimen. 3. To study the trajectories of molecular measurable residual disease (MRD) during the therapy. 4. To evaluate the impact of baseline genomic alterations on response and survival of the combination regimen. 5. To assess the duration of response, overall survival (OS) and event free survival (EFS) of patients. OUTLINE: INDUCTION: Patients with newly diagnosed CBFβ::MYH11(+) AML receive 2 cycles of VEN/HMA as induction therapy. Venetoclax orally (PO) once daily (QD) on days 1-28, azacitidine subcutaneously (SC) on days 1-7 or decitabine intravenously (IV) over 30-60 minutes on days 1-5. CONSOLIDATION: Patient fitness will be reassessed according to the Ferrara criteria if CR or CRi is achieved after 2 cycles of VEN/HMA. Fit patients will receive four cycles of consolidation therapy with high-dose cytarabine (2g/m2 every 12 hours, on days 1-3) combined with venetoclax (on days 1-7). Unfit patients will continue to receive VEN/HMA until disease progression. After completion of study treatment, patients are followed up at 30 days and then every 3 months thereafter. ### Conditions Module **Conditions:** - Acute Myeloid Leukemia **Keywords:** - venetoclax - acute myeloid leukemia ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 40 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** INDUCTION: Patients receive 2 cycles of VEN/HMA as induction therapy. Venetoclax orally (PO) once daily (QD) on days 1-28, azacitidine subcutaneously (SC) on days 1-7 or decitabine intravenously (IV) over 30-60 minutes on days 1-5. CONSOLIDATION: Fit patients will receive four cycles of consolidation therapy with high-dose cytarabine (2g/m2 every 12 hours, on days 1-3) combined with venetoclax (on days 1-7). Unfit patients will continue to receive VEN/HMA until disease progression. **Intervention Names:** - Drug: Venetoclax - Drug: azacitidine - Drug: decitabine - Drug: Cytarabine **Label:** Venetoclax, Azacitidine/Decitabine/, Cytarabine **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Venetoclax, Azacitidine/Decitabine/, Cytarabine **Description:** Given PO, once daily. Treatment in cycle 1, the dose is 100 mg on day 1, then ramp up to 400mg. In all subsequent cycles, the dose of venetoclax is initiated at 400 mg daily. **Name:** Venetoclax **Other Names:** - ABT-199 - ABT199 - Venclexta **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Venetoclax, Azacitidine/Decitabine/, Cytarabine **Description:** Given SC **Name:** azacitidine **Other Names:** - 5 AZC - 5-AZC **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Venetoclax, Azacitidine/Decitabine/, Cytarabine **Description:** Given IV **Name:** decitabine **Other Names:** - Dacogen **Type:** DRUG #### Intervention 4 **Arm Group Labels:** - Venetoclax, Azacitidine/Decitabine/, Cytarabine **Description:** Given IV **Name:** Cytarabine **Other Names:** - 1-.beta.-Cytosine arabinoside - Ara-C **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** CR/CRi rate will be determined. **Measure:** composite complete remission rate **Time Frame:** after 2 cycles of induction therapy with VEN/HMA (each cycle is 28 days). #### Secondary Outcomes **Description:** ORR will be determined. **Measure:** Overall response rate (ORR) **Time Frame:** after 2 cycles of induction therapy with VEN/HMA (each cycle is 28 days). **Description:** Safety profile based on NCI CTCAE version 5.0 will be determined. **Measure:** Incidence of adverse events **Time Frame:** From the start of treatment until death or last follow-up, assessed for up to 3 years. **Description:** MRD will be assessed by real-time qRCR. **Measure:** measurable residual disease (MRD) negativity **Time Frame:** From the start of treatment until death or last follow-up, assessed for up to 3 years. **Description:** The impact of concurrent gene mutations ( analysis via an 81-gene institutional next-generation sequencing platform) on response and the survival of the combination regimen will be assessed. **Measure:** Impact of concurrent gene mutations **Time Frame:** Baseline **Description:** OS will be assessed. **Measure:** Overall survival (OS) **Time Frame:** From the start of treatment until death or last follow-up, assessed for up to 3 years. **Description:** EFS will be assessed. **Measure:** Event-free survival (EFS) **Time Frame:** up to 3 years. **Description:** DOR will be assessed. **Measure:** Duration of response (DOR) **Time Frame:** up to 3 years. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Adults ≥ 18 years. 2. Newly diagnosed CBFβ::MYH11(+) AML. 3. Performance status 0-3 on the Eastern Cooperative Oncology Group (ECOG) Scale. 4. Subject must voluntarily sign and date an informed consent, prior to the initiation of any screening or study-specific procedures. Ferrara's criteria are used to determine whether a patient is unfit, and a patient is deemed unfit if at least one of the following criteria is met: 1. Age\>75 years. 2. There are serious underlying heart, lung, kidney, liver complications. 3. There are active infections that do not respond to anti-infective therapy. 4. There is cognitive impairment. 5. Other comorbidities that the doctor determines are not suitable for intensive chemotherapy. Exclusion Criteria: 1. Subject has received treatment with a hypomethylating agent and/or other chemotherapeutic agents either conventional or experimental or targeted drug therapy for AML (except oral hydroxyurea and/or leukocytometry to reduce white blood cell count). 2. Pregnant or lactating women. 3. To the knowledge of the subject and investigator, subject may not be able to complete all study visits or procedures required by the study protocol, including follow-up visits, and/or be unable to comply with the required study procedures. 4. Other conditions deemed unsuitable for participation in this study by the investigator. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Ying Wang **Phone:** 008613656214782 **Role:** CONTACT #### Locations **Location 1:** **City:** Suzhou **Contacts:** ***Contact 1:*** - **Name:** Zhou-lin Lu - **Phone:** 008613914086271 - **Role:** CONTACT **Country:** China **Facility:** Ethical Committee of the First Affiliated Hospital of Soochow University **State:** Jiangsu **Status:** RECRUITING **Zip:** 215000 **Location 2:** **City:** Suzhou **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Ying Wang - **Phone:** 008613656214782 - **Role:** CONTACT **Country:** China **Facility:** The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology **State:** Jiangsu **Status:** RECRUITING **Zip:** 215000 #### Overall Officials **Official 1:** **Affiliation:** The First Affiliated Hospital of Soochow University **Name:** Ying Wang **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000006402 - Term: Hematologic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10945 - Name: Leukemia - Relevance: HIGH - As Found: Leukemia - ID: M10955 - Name: Leukemia, Myeloid - Relevance: HIGH - As Found: Myeloid Leukemia - ID: M18127 - Name: Leukemia, Myeloid, Acute - Relevance: HIGH - As Found: Acute Myeloid Leukemia - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M9490 - Name: Hematologic Diseases - Relevance: LOW - As Found: Unknown - ID: T3995 - Name: Myeloid Leukemia - Relevance: HIGH - As Found: Myeloid Leukemia - ID: T182 - Name: Acute Myeloid Leukemia - Relevance: HIGH - As Found: Acute Myeloid Leukemia - ID: T188 - Name: Acute Non Lymphoblastic Leukemia - Relevance: HIGH - As Found: Acute Myeloid Leukemia - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007938 - Term: Leukemia - ID: D000007951 - Term: Leukemia, Myeloid - ID: D000015470 - Term: Leukemia, Myeloid, Acute ### Intervention Browse Module - Ancestors - ID: D000000964 - Term: Antimetabolites, Antineoplastic - ID: D000000963 - Term: Antimetabolites - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000970 - Term: Antineoplastic Agents - ID: D000000998 - Term: Antiviral Agents - ID: D000000890 - Term: Anti-Infective Agents - ID: D000007166 - Term: Immunosuppressive Agents - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000004791 - Term: Enzyme Inhibitors ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M6766 - Name: Cytarabine - Relevance: HIGH - As Found: Multi- - ID: M249656 - Name: Venetoclax - Relevance: HIGH - As Found: Presence - ID: M1697 - Name: Decitabine - Relevance: HIGH - As Found: Marrow - ID: M4673 - Name: Azacitidine - Relevance: HIGH - As Found: Frequency - ID: M4281 - Name: Antimetabolites - Relevance: LOW - As Found: Unknown - ID: M4314 - Name: Antiviral Agents - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown - ID: M10212 - Name: Immunosuppressive Agents - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000003561 - Term: Cytarabine - ID: D000001374 - Term: Azacitidine - ID: D000077209 - Term: Decitabine - ID: C000579720 - Term: Venetoclax ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429085 **Acronym:** RAPPER IV **Brief Title:** Rex Robot Assisted Rehabilitation to Enhance Balance and Mobility for People With Multiple Sclerosis, Clinical and Biomarker Study - RAPPER IV **Official Title:** Rex Robot Assisted Rehabilitation to Enhance Balance and Mobility for People With Multiple Sclerosis, Clinical and Biomarker Study - RAPPER IV #### Organization Study ID Info **ID:** Protocol Version 2.0 #### Organization **Class:** OTHER_GOV **Full Name:** East Kent Hospitals University NHS Foundation Trust ### Status Module #### Completion Date **Date:** 2020-03-31 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2020-03-31 **Type:** ACTUAL #### Start Date **Date:** 2018-12-18 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Study First Submit Date:** 2024-05-13 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** Rex Bionics #### Lead Sponsor **Class:** OTHER_GOV **Name:** East Kent Hospitals University NHS Foundation Trust #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Multiple Sclerosis (MS) poses challenges to balance and mobility, impacting the daily lives of affected individuals. The RAPPER IV study is a clinical trial to evaluate a balance and mobility training intervention supported by a powered Rex robotic exoskeleton for people living with MS. Aims and objectives: This study aims to gain an insight into the potential health benefits of using a Rex robot to assist in a neuro-rehabilitation intervention program focused on improving balance and functional mobility with supervision from a specialist clinician. Objectives * to evaluate the feasibility of using the Rex robotic walking device for rehabilitation with people who have mobility restrictions due to Multiple Sclerosis (MS) * to assess and evaluate the clinical effectiveness of a 5-week robotic assisted exercise program focused on core stability exercises, balance and walking using patient related outcome measures * to gain an insight into the experiences of participants and their spouses of using the robotic walking device for rehabilitation and how this has impacted on their lives A single cohort group of 20 people who were living with MS who met trial eligibility criteria were recruited. A variety of clinical outcome measurements were taken pre, during and post trial and results were analysed by a statistician. **Detailed Description:** The key research questions: * Is it feasible for a person with balance and mobility impairment caused by MS to use a robotic walking device to exercise in standing and walking with supervision safely? * What are the key outcome measures most sensitive to measurable change in this study population sample, which may reflect potential improvement during the trial period? (Clinical outcome scales and self-reported questionnaires) * Is this robotic assisted balance and mobility training program feasible, safe and effective? * Does the completion of this balance and mobility exercise treatment intervention result in measurable improvements in balance, mobility, spasticity, lower limb joint range of movement and achievable individual patient goals? To answer these questions, we invited 20 people diagnosed with MS (as defined by "McDonald" criteria, Polman et al, 2011) to undertake a 5-week balance exercise intervention program supported by the use of the Rex robotic walking device, designed to strengthen their postural body and leg muscles and improve their balance. Participants were monitored and progressed on an individual basis throughout the treatment program as appropriate and a range of standardised assessments, questionnaires and relevant clinical outcome scales were used to capture and measure change related to this trial. Prospective, open label, single arm, non-randomized, non-comparative feasibility study of Rex robot assisted training to improve balance, mobility and cardiovascular fitness for people living with MS. A purposive sample of 20 adults, who have a primary diagnosis of MS, aged between 18 and 80 years old, with an Expanded Disability Status Scale (EDSS) as defined by Kurtzke (1983), with scores between 4 and 6.5 were recruited into this study. ### Conditions Module **Conditions:** - Multiple Sclerosis **Keywords:** - Balance - Core stability - Mobility - Powered exoskeleton - Neuro-rehabilitation ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP **Intervention Model Description:** Prospective, open label, single arm, non-randomized, non-comparative feasibility study of Rex robot assisted training to improve balance and mobility for people living with MS. ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 20 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Use of powered Rex robotic exoskeleton to enable the practice of core stability balance exercises **Intervention Names:** - Device: Rex robotic assisted balance exercises **Label:** People diagnosed with Multiple Sclerosis **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - People diagnosed with Multiple Sclerosis **Description:** Individual is supported by a Rex robotic exoskeleton which enables assisted and supervised practise of balance exercises. This intervention took place as a supported and supervised series of 5 sessions over 5 weeks as an Out-patient. **Name:** Rex robotic assisted balance exercises **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Timed transfer into the Rex device with appropriate level of assistance **Measure:** Timed transfer into the Rex device **Time Frame:** Time point 1 - Week 1 **Description:** Completion of sit to stand and stand to sit within the Rex device with hands on assistance from trial therapist **Measure:** Completion of sit to stand and stand to sit within the Rex device **Time Frame:** Time point 1 - Week 1 **Description:** Completion of 1 Rex robotic assisted balance rehabilitation exercise session with hands on assistance from trial therapist **Measure:** Completion of 1 Rex robotic assisted balance rehabilitation exercise session **Time Frame:** Time point 1 - Week 1 **Description:** Number of individuals screened and those eligible who entered the trial and those who completed the trial **Measure:** Screening loss analysis **Time Frame:** End of recruitment period - Week 30 #### Secondary Outcomes **Description:** Timed up and Go **Measure:** Timed up and Go **Time Frame:** Time point 1 - Week 1 **Description:** Berg Balance Scale **Measure:** Berg Balance Scale **Time Frame:** Measured at 3 time points: Weeks 1, 6 and 10 **Description:** Visual Analog Scale (Pain) **Measure:** Visual Analog Scale (Pain) **Time Frame:** Measured at 2 time points: Weeks 1 and 6 **Description:** Balance and falls risk **Measure:** Modified Falls Efficacy Scale **Time Frame:** Measured at 2 time points: Weeks 1 and 6 **Description:** Balance and confidence in balance **Measure:** Activities-specific Balance Confidence scale **Time Frame:** Measured at 2 time points: Weeks 1 and 6 **Description:** Perception of impact of spasticity on life **Measure:** Spasticity Impact Scale **Time Frame:** Measured at 2 time points: Weeks 1 and 6 **Description:** Perceived Health Related Quality of Life **Measure:** EQ-5D-5L **Time Frame:** Measured at 2 time points: Weeks 1 and 6 **Description:** Perceived impact of MS on life **Measure:** MSIS-29 **Time Frame:** Measured at 2 time points: Weeks 1 and 6 **Description:** Joint range of movement **Measure:** Joint range of movement **Time Frame:** Measured at 2 time points: Weeks 1 and 6 **Description:** Goal Attainment Scale **Measure:** Goal Attainment Scale **Time Frame:** Set at Week 1 and measured and reviewed at Week 25 **Description:** Modified Ashworth Scale for muscle spasticity **Measure:** Modified Ashworth Scale **Time Frame:** Measured at 2 time points: Weeks 1 and 6 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * • Are aged greater than 18 years and less than 80 years * Have a confirmed diagnosis of MS by a Consultant Neurologist as per McDonald Criteria. * Have moderate mobility restriction as defined by an Extended Disability Status Scale (EDSS) score of between 4 to 6.5 * Ten participants to be recruited from EDSS 4 to 5.5 * Ten participants to be recruited from EDSS 5.5 to 6.5 * Within the anthropometric requirements of the REX device (See 'RAPPER III- MS 014 TF-04 v 3.0 REX Clinical Assessment Guide A4' for details of weight, height, size and range of motion requirements) * Offer written informed consent to take part in the study Exclusion Criteria: * a history of osteoporosis or osteoporosis related bone fractures. * skin integrity issues that could be adversely affected by the REX device * severe hypertonia (spasticity) as indicated by a score equal to or greater than 4 on the modified Ashworth scale for any muscle in their lower limbs. * a behavioural, cognitive or communication impairment which could interfere with the ability to participate in a rehabilitation program, as noted during screening (e.g., agitation, inability to follow two step commands) * are unable or unwilling to provide informed consent * are considered medically unsuitable for rehabilitation in the opinion of the screening medical specialist * a known allergy (skin contact) to materials used in Rex * are pregnant * taking part in any other medical research trial at the same time **Maximum Age:** 79 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Canterbury **Country:** United Kingdom **Facility:** East Kent Hospitals University NHS Trust **State:** Kent ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Zajicek J, Fox P, Sanders H, Wright D, Vickery J, Nunn A, Thompson A; UK MS Research Group. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. Lancet. 2003 Nov 8;362(9395):1517-26. doi: 10.1016/S0140-6736(03)14738-1. **PMID:** 14615106 **Citation:** Straudi S, Fanciullacci C, Martinuzzi C, Pavarelli C, Rossi B, Chisari C, Basaglia N. The effects of robot-assisted gait training in progressive multiple sclerosis: A randomized controlled trial. Mult Scler. 2016 Mar;22(3):373-84. doi: 10.1177/1352458515620933. Epub 2015 Dec 10. **PMID:** 26658817 **Citation:** Bethoux F, Bennett S. Introduction: enhancing mobility in multiple sclerosis. Int J MS Care. 2011 Spring;13(1):1-3. doi: 10.7224/1537-2073-13.1.1. No abstract available. **PMID:** 24453699 **Citation:** Latimer-Cheung AE, Pilutti LA, Hicks AL, Martin Ginis KA, Fenuta AM, MacKibbon KA, Motl RW. Effects of exercise training on fitness, mobility, fatigue, and health-related quality of life among adults with multiple sclerosis: a systematic review to inform guideline development. Arch Phys Med Rehabil. 2013 Sep;94(9):1800-1828.e3. doi: 10.1016/j.apmr.2013.04.020. Epub 2013 May 10. **PMID:** 23669008 **Citation:** Donze C. Update on rehabilitation in multiple sclerosis. Presse Med. 2015 Apr;44(4 Pt 2):e169-76. doi: 10.1016/j.lpm.2014.10.019. Epub 2015 Mar 4. **PMID:** 25746432 **Citation:** Wiles CM, Newcombe RG, Fuller KJ, Shaw S, Furnival-Doran J, Pickersgill TP, Morgan A. Controlled randomised crossover trial of the effects of physiotherapy on mobility in chronic multiple sclerosis. J Neurol Neurosurg Psychiatry. 2001 Feb;70(2):174-9. doi: 10.1136/jnnp.70.2.174. **PMID:** 11160464 **Citation:** Cattaneo D, Jonsdottir J, Zocchi M, Regola A. Effects of balance exercises on people with multiple sclerosis: a pilot study. Clin Rehabil. 2007 Sep;21(9):771-81. doi: 10.1177/0269215507077602. **PMID:** 17875557 **Citation:** Birch N, Graham J, Priestley T, Heywood C, Sakel M, Gall A, Nunn A, Signal N. Results of the first interim analysis of the RAPPER II trial in patients with spinal cord injury: ambulation and functional exercise programs in the REX powered walking aid. J Neuroeng Rehabil. 2017 Jun 19;14(1):60. doi: 10.1186/s12984-017-0274-6. **PMID:** 28629390 **Citation:** Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983 Nov;33(11):1444-52. doi: 10.1212/wnl.33.11.1444. **PMID:** 6685237 **Citation:** Sakel M, Saunders K, Hodgson P, Stephensen D, Phadke CP, Bassett PA, Wilkinson D. Feasibility and Safety of a Powered Exoskeleton for Balance Training for People Living with Multiple Sclerosis: A Single-Group Preliminary Study (Rapper III). J Rehabil Med. 2022 Dec 9;54:jrm00357. doi: 10.2340/jrm.v54.4544. **PMID:** 36484722 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000020278 - Term: Demyelinating Autoimmune Diseases, CNS - ID: D000020274 - Term: Autoimmune Diseases of the Nervous System - ID: D000009422 - Term: Nervous System Diseases - ID: D000003711 - Term: Demyelinating Diseases - ID: D000001327 - Term: Autoimmune Diseases - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M12060 - Name: Multiple Sclerosis - Relevance: HIGH - As Found: Multiple Sclerosis - ID: M15415 - Name: Sclerosis - Relevance: HIGH - As Found: Sclerosis - ID: M4629 - Name: Autoimmune Diseases - Relevance: LOW - As Found: Unknown - ID: M22098 - Name: Demyelinating Autoimmune Diseases, CNS - Relevance: LOW - As Found: Unknown - ID: M22094 - Name: Autoimmune Diseases of the Nervous System - Relevance: LOW - As Found: Unknown - ID: M6909 - Name: Demyelinating Diseases - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000009103 - Term: Multiple Sclerosis - ID: D000012598 - Term: Sclerosis ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429072 **Acronym:** I-MASS **Brief Title:** Integration of Mindfulness and Acupuncture After Spine Surgery **Official Title:** Integration of Mindfulness and Acupuncture After Spine Surgery: Aim 2 #### Organization Study ID Info **ID:** Pro00114814 #### Organization **Class:** OTHER **Full Name:** Duke University ### Status Module #### Completion Date **Date:** 2025-08-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2025-05-01 **Type:** ESTIMATED #### Start Date **Date:** 2024-06-01 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Study First Submit Date:** 2024-03-04 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Duke University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** The Integration of mHealth Mindfulness and auricular Acupuncture (AA) for individuals undergoing Spine Surgery (I-MASS) is a novel combination of integrative treatments to address postsurgical pain. This is a single-site, two-arm randomized feasibility and acceptability pilot trial of the I-MASS program plus enhanced patient education compared to enhanced patient education alone in patients undergoing spine surgery. Outcomes data will come from a combination of passive electronic health record data augmented with patient-reported data collected through the Pattern Health app (the mHealth platform used for delivering mindfulness training and collecting data). Outcomes will focus on feasibility and acceptability of I-MASS, feasibility of recruitment and retention strategies, and data collection procedures through both the Lift app and electronic health record. Feasibility will be supported by mindfulness module completion rates, acupuncture visits attended, participant retention, and questionnaire completion rates. Acceptability will be supported by patient-reported satisfaction, acceptability and usability thresholds. **Detailed Description:** Participants will be randomized to one of two study arms: 1) the I-MASS program plus enhanced education or 2) the enhanced education intervention only. Overview of I-MASS: The I-MASS program includes pre-surgical and post-surgical components. I-MASS begins with one introductory telephone call by a mindfulness coach (co-I Gremore) within 1 week of the patient scheduling surgery to introduce the participant to the Pattern Health app, discuss the benefits of combining mindfulness and AA, discuss how to access the Healthwise educational content, and lead a brief (\~10 min) mindfulness exercise, as desired. Thereafter, participants will complete 4 self-directed mindfulness modules through the Pattern Health app (1 prior to surgery, 3 following surgery). The initial AA session will occur within one week prior to surgery. The second AA session will occur within the first week following surgery. Afterwards, participants will receive AA in participating community outpatient clinics for up to 8 sessions total within 12 weeks of surgery. The investigators will allow flexibility in scheduling these visits with a window of 5-10 days between AA sessions. Using push notifications, the Pattern Health app will remind patients when they are within their window for AA treatment. Details of AA delivery: AA will be performed by formally trained and certified acupuncturists in the community contracted with Duke to provide services for this trial. AA will involve the placement of needles in up to 5 sites (Cingulate Gyrus, Thalamus, Omega 2, Shen Men, and Point Zero) on each ear corresponding to the previously developed battlefield acupuncture protocol to treat pain. Points are always inserted in the same order and the number of needles inserted is determined by the patient's change in pain level. The AA protocol includes pain assessment before starting, after each needle is placed as that informs how many needles are placed, and at the end of the session. The protocol will include use of semi-permanent needles (Seirin Pyonex press-tacks (0.2x1.5mm) or ASP needles). These needles can remain in place for several days for continued pain relief. Participants will be instructed to remove the needles 2 days before their next visit, or sooner if site irritation or soreness warrants. Prior research has demonstrated consistency of acupuncture outcomes across different providers, however the specific components of each acupuncture treatment will be recorded according to the revised Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) to allow for post-hoc assessment of treatment fidelity. Follow-up acupuncture visits will be scheduled with the study acupuncturists. If participants are unable to tolerate aurcular acupuncture, they will be offered the option of a more traditional full body acupuncture protocol focused on pain management. Details of the Pattern Health app and mHealth mindfulness training: Mindfulness training via the Pattern Health app will be modeled after the protocol used in prior studies of this app with patients recovering from critical illness. Introductory call. All participants in the I-MASS treatment arm will receive an initial introductory call with a mindfulness coach. Each \~30-minute introductory call will be composed of four parts: (1) brief discussion about participants' major current stressor(s); (2) rationale and discussion of the didactic focus; (3) practice and review, and (4) discussion about participant's use of mindfulness skills, challenges in applying the skills, how these skills integrate with the use of AA, and how to maintain progress. The coach will answer questions about use and navigation of the app, and review the overall timeline for completion of the self-directed modules. Mindfulness modules. Study participants will complete 4 self-directed mindfulness training modules (called the Lift program) through the Pattern Health app (1 prior to surgery, 3 following surgery). The training will include a guided series of videos, audio files and interactive text features. Each week-long module includes daily sessions comprised of a short (4-5 min) background video, a 6-8 min guided mediation (users could choose either a female or male voice) and interactive suggestions for how to apply mindfulness within their daily routine (\~10-12 min total per session). The pre-operative training (module 1) focuses on developing an awareness of breath, which is a fundamental mindfulness technique. Following surgery, participants will initiate training module 2, building awareness of body systems, followed by modules 3 and 4 over the subsequent 2 weeks. Automated activity reminders in the app will alert the participant to complete the daily session. Each module builds upon skills learned in the previous module and participants are encouraged to continue using learned skills and resources within the app after completion of the modules. Acupuncturists will also be trained to facilitate discussion about mindful awareness and non-judgmental thoughts regarding pain, giving participants an opportunity to reflect on their experiences during the AA session. Enhanced Education: The program consists of education prior to and after surgery for all participants. This will constitute the only intervention in the education only arm. All of the educational material is delivered via the Pattern Health App. All educational content is from the Healtwise.net Duke Health Library (https://www.healthwise.net/dukehealth/Content) and is carefully selected with input by surgeons to be delivered during the appropriate phase of recovery. Educational topics include learning how to lift and sit when experiencing pain, proper precautions following surgery, how to ease back into daily activities following surgery, and ways to self-manage pain. Education is in the form of short reading materials or videos, all designed to help safely and effectively recover from surgery. Participants in the trial will not be prevented from receiving any other care deemed necessary by their health care team and surgeon. This program is designed to complement their usual care, not replace it. Participant involvement with the study will be complete at 3 months following surgery. The will be able to receive up to 8 acupuncture sessions total (cost covered by the study) during their time in the study. All questionnaires will be administered through the Pattern Health app. ### Conditions Module **Conditions:** - Single Level Spinal Fusion - Discetomy - Laminectomy ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** OTHER #### Enrollment Info **Count:** 50 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Integrated program that combines Mindfulness Based Stress Reduction (MBSR) delivered via mobile app (mHealth) with auricular Acupuncture (AA) in individuals undergoing Spine Surgery (I-MASS) plus enhanced education. I-MASS begins with one introductory telephone call by a mindfulness coach within 1 week of the patient scheduling surgery to introduce the participant to the Pattern Health app, discuss the benefits of combining mindfulness and AA (auricular acupuncture), discuss how to access the Healthwise educational content, and lead a brief (\~10 min) mindfulness exercise, as desired. Thereafter, participants will complete 4 self-directed mindfulness modules through the Pattern Health app (1 prior to surgery, 3 following surgery). **Intervention Names:** - Behavioral: Mindfulness Based Stress Reduction (MBSR) - Other: Auricular acupuncture - Behavioral: Enhanced education **Label:** I-MASS Program plus Enhanced Education **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** The program consists of education prior to and after surgery for all participants. All of the educational material is delivered via the Pattern Health App. All educational content is from the Healthwise.net Duke Health Library (https://www.healthwise.net/dukehealth/Content) and is carefully selected with input by surgeons to be delivered during the appropriate phase of recovery. Education is in the form of short reading materials or videos, all designed to help safely and effectively recover from surgery. **Intervention Names:** - Behavioral: Enhanced education **Label:** Enhanced Education Intervention Only **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - I-MASS Program plus Enhanced Education **Description:** Each mindfulness module is anticipated to last one week and includes a short (4-5 min) introductory video, daily sessions comprised of a 6-8 min guided mediation, and interactive suggestions for how to apply mindfulness within a daily routine (\~10-12 min total per daily session). **Name:** Mindfulness Based Stress Reduction (MBSR) **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - I-MASS Program plus Enhanced Education **Description:** This technique involves inserting tiny needles in specific areas of the outer ear to target points believed to influence pain. **Name:** Auricular acupuncture **Type:** OTHER #### Intervention 3 **Arm Group Labels:** - Enhanced Education Intervention Only - I-MASS Program plus Enhanced Education **Description:** Educational topics include learning how to lift and sit when experiencing pain, proper precautions following surgery, how to ease back into daily activities following surgery, and ways to self-manage pain. **Name:** Enhanced education **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** The CSQ-8 assesses credibility and satisfaction with health-related services (8 items, 4-point Likert, with higher scores indicating higher credibility/satisfaction). **Measure:** Client Satisfaction Questionnaire (CSQ-8) **Time Frame:** up to 6 months **Description:** The SUS is ten-item attitude Likert scale (5 response options; from Strongly agree to Strongly disagree) giving a global view of subjective assessments of usability. It provides a single score on a scale of 0-100, with higher scores indicating better usability. **Measure:** System Usability Scale (SUS) **Time Frame:** up to 6 months #### Secondary Outcomes **Description:** Measure of self-reported physical function that uses 4 items of the 29-item PROMIS short form. This includes the functioning of one's upper extremities (dexterity), lower extremities (walking or mobility), and central regions (neck, back), as well as instrumental activities of daily living, such as running errands. **Measure:** PROMIS (Patient-Reported Outcomes Measurement Information System) Physical Function **Time Frame:** up to 6 months **Description:** The BPI uses a 0 to 10 numeric rating scale for item rating. Pain severity can be measured from the average of the four severity items: 1-4 = Mild Pain, 5-6 = Moderate Pain, 7-10 = Severe Pain **Measure:** Brief Pain Inventory 4-item Severity Scale (BPI) **Time Frame:** up to 6 months **Description:** The PROMIS Pain Interference instrument measures the self-reported consequences of pain across aspects of life including social, cognitive, emotional, physical and recreational activities; this instrument refers to the past seven days. This validated scale has five response options, with scores ranging from one to five. **Measure:** PROMIS Pain Interference **Time Frame:** up to 6 months **Description:** OSPRO-YF is a 10-item multidimensional assessment tool for general and pain-related psychological distress. The tool is capable of accurately estimating scores on 11 full-length psychological questionnaires measuring constructs of depression, anxiety, anger, fear avoidance beliefs for work and physical activity, kinesiophobia, pain anxiety, self-efficacy for rehabilitation, pain self-efficacy and chronic pain acceptance. **Measure:** Optimal Screening for Prediction of Referral and Outcome Yellow Flag (OSPRO-YF) Assessment Tool **Time Frame:** up to 6 months **Description:** PROMIS Sleep Disturbance measures concepts such as trouble staying asleep, not getting enough sleep, restlessness, feeling refreshed after sleep, and difficulty falling asleep in 'the past 7 days'. **Measure:** PROMIS Sleep Disturbance **Time Frame:** up to 6 months **Description:** The Q-LES-Q is a validated 14-item scale to measure satisfaction with function at work, household duties, school, leisure, social relations, and general activities over the past week. **Measure:** Quality of Life Enjoyment and Satisfaction Questionnaire (QLES- Q) **Time Frame:** up to 6 months **Description:** Medication prescriptions for Opioids, Benzodiazepines, Gabapentin/Neurontin, and NSAIDs from the time of enrollment until 6 months. Presented as morphine equivalents. **Measure:** Change in number of Medication Prescriptions **Time Frame:** baseline, up to 6 months **Measure:** Number of emergency room visits **Time Frame:** up to 6 months **Measure:** Number of hospital readmissions related to spine surgery **Time Frame:** up to 6 months **Description:** The MAAS is a 15-item scale designed to assess a core characteristic of dispositional mindfulness, namely, open or receptive awareness of and attention to what is taking place in the present. **Measure:** Mindful Attention Awareness Scale (MAAS) **Time Frame:** up to 6 months **Description:** Persistent postsurgical pain defined as chronic pain that develops or increases in intensity after a surgical procedure or a tissue injury and persists beyond the healing process, i.e., at least 3 months after the surgery or tissue trauma. **Measure:** Number of participants with persistent postsurgical pain **Time Frame:** up to 6 months **Description:** Participants will rate the 3-item PEG (pain, enjoyment, and general activity) scale assessing pain severity over the past week on 0 to 10 rating scales. A PEG summary score of 12 or greater (i.e., equivalent to an average score of 4 or greater across the 3 items) indicates bothersome chronic pain, whereas a PEG score of 11 or less will classify subjects as having mild chronic pain. **Measure:** Number of participants with high impact chronic pain as measured by the PEG (pain, enjoyment, and general activity) scale **Time Frame:** up to 6 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. undergoing single level fusion, discectomy or laminectomy of the cervical or lumbar spine for management of pain 2. 18 years of age or older 3. has access to a smartphone or mobile device (with android or iOS operating system) and internet to complete training and questionnaires. Exclusion Criteria: 1. have conditions making consent, follow-up data collection and/or use of the intervention prohibitive (e.g., Non-English speaking, serious psychiatric conditions \[i.e., schizophrenia\], traumatic brain injury, or dementia-type illness) 2. undergoing surgery for neoplastic disease 3. current daily opioid use greater than 100mg morphine equivalents 4. unable to receive acupuncture due to injury, infection, or other contraindication to the use of needles at acupuncture sites 5. not possible to attend outpatient clinic for AA follow-up (e.g., from out-of-state) 6. currently practicing mindfulness or receiving acupuncture 7. in Hospice, receiving palliative care. **Maximum Age:** 80 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Durham **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Suzanne Finley, EMT-P - **Phone:** 919-684-5431 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Cassandra Rhodes, ATC - **Phone:** 9196842042 - **Role:** CONTACT ***Contact 3:*** - **Name:** Trevor Lentz, PhD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** Duke Sports Science Institute **State:** North Carolina **Zip:** 27705 #### Overall Officials **Official 1:** **Affiliation:** Duke University **Name:** Trevor Lentz, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429059 **Brief Title:** ROAR-DIGAP: A Widely Inclusive, Largely Virtual Pilot Trial Utilizing DIGAP (Deep Integrated Genomics Analysis Platform) To Personalize Treatments **Official Title:** ROAR-DIGAP: A Widely Inclusive, Largely Virtual Pilot Trial Utilizing DIGAP (Deep Integrated Genomics Analysis Platform) To Personalize Treatments #### Organization Study ID Info **ID:** Pro00114385 #### Organization **Class:** OTHER **Full Name:** Duke University ### Status Module #### Completion Date **Date:** 2026-06-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-31 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-30 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2026-06-01 **Type:** ESTIMATED #### Start Date **Date:** 2024-06-01 **Type:** ESTIMATED **Status Verified Date:** 2024-04 #### Study First Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Study First Submit Date:** 2024-04-09 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Temple University #### Lead Sponsor **Class:** OTHER **Name:** Duke University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Is US Export:** False ### Description Module **Brief Summary:** GenieUs developed an analysis platform that will be tested to separate study participants with ALS into four categories based on blood work. These general categories are neuroinflammation, oxidative stress, impaired autophagy \& axonal transport, and mitochondrial dysfunction. Once a disease category is established, participants in this study will receive one of four individualized supplements for 6 months and we will determine whether these are slowing ALS progression: Astaxanthin will be given for the category of neuroinflammation, Protandim for oxidative stress, Melatonin for impaired autophagy and MitoQ for mitochondrial dysfunction. During the first 3 months, participants will have routine monitoring and in months 3 through 9 they will receive the assigned supplement. **Detailed Description:** This will be a widely inclusive, largely remote/virtual, two-center, open-label pilot trial utilizing 50 participants as their own controls. Following informed consent and screening, participants will provide demographics, disease characteristics, co-morbidities, and concomitant medications. They will have a baseline ALSFRS-R score obtained and blood will be drawn for DIGAP classification, PBMCs (which will be used to generate iPSCs from which motor neurons and/or microglia can be generated), baseline mechanistic biomarkers and baseline neurofilament light chain. A urine pregnancy test will be obtained for pre-menopausal females who have not had one by their own doctor in the past 7 days. Each month after that, they will be contacted by phone by study coordinators to review adverse events, new co-morbidities, and concomitant medications, and to generate a new ALSFRS-R score. At month 3, DIGAP classification will be revealed to each participant and based on this, they will receive 1 of 4 treatments. They will take their assigned treatment for 6 months. At months 3, 5 and 9 they will be asked to return for in person blood draws for repeat mechanistic biomarkers and neurofilament light chain measurements. All of the described blood tests and investigational treatments are being performed exclusively for research purposes. ### Conditions Module **Conditions:** - Amyotrophic Lateral Sclerosis ALS ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** At month 3, DIGAP classification will be revealed to each participant and based on this, they will receive 1 of 4 treatments. They will take their assigned treatment for 6 months. ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 50 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Study participants in this category are expected to have inflammation in their brains and spinal cords. **Intervention Names:** - Drug: Astaxanthin **Label:** Neuroinflammation **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Study participants in this category are expected to have too many damaging "free radical" chemicals in their brains and spinal cords. **Intervention Names:** - Drug: Protandim **Label:** Oxidative Stress **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Study participants in this category are expected to have motor neurons that have trouble transporting materials up and down their length, and/or trouble with the turnover of damaged proteins and intracellular structures. **Intervention Names:** - Drug: Melatonin **Label:** Impaired Autophagy and Axonal Transport **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** Study participants in this category are expected to have motor neurons that are unable to produce normal amounts of energy. **Intervention Names:** - Drug: MitoQ **Label:** Mitochondrial Dysfunction **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Neuroinflammation **Description:** Astaxanthin is a red-orange natural pigment belonging to a group of carotenoids called xanthophylls. In nature, astaxanthin is synthesized by microalgae and phytoplankton and biomagnifies in higher marine animals through the food chain. Natural astaxanthin is available as capsules, soft gels, tablets, powders, biomass, creams, energy drinks, oils and extracts and often contains other carotenoids. The compound is available as a United States Pharmacopeia (USP) verified supplement which ensures federally recognized standards for quality and purity (https://www.quality-supplements.org/verified-products/verified-products-listings). **Name:** Astaxanthin **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Oxidative Stress **Description:** Protandim is an oral tablet derived from five different plants: Silybum marianum (milk thistle), Withania somnifera (Ashwagandha), Camellia sinensis (green tea), Curcuma longa (turmeric) and Bacopa monniera. **Name:** Protandim **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Impaired Autophagy and Axonal Transport **Description:** Melatonin is a hormone that has long been known to play a role in regulating sleep. Melatonin supplements are commonly used to treat insomnia, but in recent years, melatonin has been found to play a wider role in human physiology including the potential regulation of autophagy. **Name:** Melatonin **Type:** DRUG #### Intervention 4 **Arm Group Labels:** - Mitochondrial Dysfunction **Description:** The active ingredient in MitoQ is ubiquinone, the same as found in coenzyme Q10 and idebenone. However, the ubiquinone in MitoQ is attached to a positively charged, lipophilic molecule called TPP (triphenyl phosphonium), which allows it to selectively accumulate in mitochondria. This makes it more potent than untargeted ubiquinone analogs at protecting mitochondria in cultured cells. It can be administered orally and, at least in animals, can cross the blood brain barrier and accumulate in brain mitochondria. **Name:** MitoQ **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** A quickly administered (five minute) ordinal rating scale (ratings 0-4) used to determine patients' assessments of their capability and independence in 12 functional activities. All 12 activities are relevant to people living with ALS.The ALSFRS-R declines linearly with time over a wide range during the course of ALS and it has been validated for telephone use. **Measure:** ALS Functional Rating Scale, Revised (ALSFRS-R) **Time Frame:** baseline and at each of the subsequent 9 telephone or in person visits (approximately 9 months) #### Secondary Outcomes **Description:** They are neuron-specific components of the cytoskeleton. They exist in heavy, medium, and light chain forms. Neurofilament light chain levels are elevated in the spinal fluid and the blood of patients with ALS and other neurodegenerative diseases, and higher levels predict more severe disease progression. These levels rise dramatically when asymptomatic carriers of ALS-causing genetic mutations begin to convert to an ALS phenotype. **Measure:** Neurofilament Light Chain levels **Time Frame:** baseline, month 3, month 5 (2 months into treatment) and month 9 (6 months into treatment) **Description:** Used to measure neuroinflammation. These are known to be abnormal in patients with ALS, their levels correlate with disease progression and they can be altered by drugs in trials. **Measure:** Neuroinflammation measured by C-reactive protein (CRP) **Time Frame:** baseline, 3 months, 5 months and 9 months **Description:** Used to measure neuroinflammation. These are known to be abnormal in patients with ALS, their levels correlate with disease progression and they can be altered by drugs in trials. **Measure:** Neuroinflammation measured by monocyte chemoattractant protein-1 (MCP-1) **Time Frame:** baseline, 3 months, 5 months and 9 months **Description:** Used to measure neuroinflammation. These are known to be abnormal in patients with ALS, their levels correlate with disease progression and they can be altered by drugs in trials. **Measure:** Neuroinflammation measured by chitotriosidase (CHIT1) **Time Frame:** baseline, 3 months, 5 months and 9 months **Description:** Used to measure oxidative stress. **Measure:** Oxidative stress measured by total antioxidant capacity (TAC) **Time Frame:** baseline, 3 months, 5 months and 9 months **Description:** Uric acid is an antioxidant and levels of uric acid have been reported to be lower in ALS subjects and correlated with progression. It has also been shown to be responsive to treatments in trials **Measure:** Oxidative stress measured by uric acid levels. **Time Frame:** baseline, 3 months, 5 months and 9 months **Description:** To measure impaired autophagy, we will use Beclin-1. This highly conserved eukaryotic protein has a major regulatory role in autophagy. It is a component of the phosphatidylinositol-3-kinase (PI3K) complex which mediates vesicle-trafficking thereby inducing autophagy. Beclin-1 dysfunction has been implicated in many disorders, including cancer and neurodegenerative diseases **Measure:** Impaired autophagy measured by Beclin-1 **Time Frame:** baseline, 3 months, 5 months and 9 months **Description:** Compromised mitochondrial oxidative phosphorylation shifts the cellular bioenergetic system to anaerobic respiration and increases the level of lactate. Lactate has been used as a biomarker for mitochondrial disease in many previous studies. **Measure:** Mitochondrial dysfunction measured by lactate. **Time Frame:** baseline, 3 months, 5 months and 9 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Male or female aged at least 18 years. 2. Sporadic or familial ALS diagnosed as per Gold Coast Criteria. 3. Patient is able to understand and express informed consent (in the opinion of the site investigator). 4. Patient is able to read and write English. 5. Patient is expected to survive for the duration of the trial. 6. Able to swallow tablets at enrollment and expected to be able to swallow tablets for the duration of the trial. 7. Women must not be pregnant (will have evidence of a negative pregnancy test obtained by study team at baseline, or by local physician within past 7 days or be post-menopausal) 8. Women must not be able to become pregnant (e.g., post-menopausal, surgically sterile, or using adequate birth control methods) for the duration of the study and three months after study completion. Adequate contraception includes abstinence, hormonal contraception (oral contraception, implanted contraception, injected contraception, or other hormonal contraception, for example patch or contraceptive ring), intrauterine device (IUD) in place for ≥ 3 months, barrier method in conjunction with spermicide, or another adequate method. Exclusion Criteria: 1. Actively or recently (within past 30 days) participating in another intervention trial. 2. Currently or recently (within 30 days) taking any of the 4 investigational treatments being used in this trial. 3. Prior side effects from any of the 4 investigational treatments being used in this trial. 4. Patient has a medical or psychiatric illness that could in the investigator's opinion interfere with the patient's ability to participate in this study. 5. Pregnant women or women currently breastfeeding. 6. Life expectancy shorter than the duration of the trial. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Michelle ward, RN **Phone:** 919-613-2681 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Hailey Zampa **Phone:** 919-613-2681 **Role:** CONTACT #### Locations **Location 1:** **City:** Durham **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Michelle Ward, RN - **Phone:** 919-613-2681 - **Role:** CONTACT ***Contact 2:*** - **Name:** Richard Bedlack, MD, PhD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** Duke University Medical Center **State:** North Carolina **Zip:** 27705 **Location 2:** **City:** Philadelphia **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** John Furey - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Christopher Pizzica - **Role:** CONTACT ***Contact 3:*** - **Name:** Terry Heiman-Patterson, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** Temple University **State:** Pennsylvania **Zip:** 19122 ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000019636 - Term: Neurodegenerative Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000009468 - Term: Neuromuscular Diseases - ID: D000013118 - Term: Spinal Cord Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000057177 - Term: TDP-43 Proteinopathies - ID: D000057165 - Term: Proteostasis Deficiencies - ID: D000008659 - Term: Metabolic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M15415 - Name: Sclerosis - Relevance: LOW - As Found: Unknown - ID: M18879 - Name: Motor Neuron Disease - Relevance: HIGH - As Found: Lateral Sclerosis - ID: M4024 - Name: Amyotrophic Lateral Sclerosis - Relevance: HIGH - As Found: Amyotrophic Lateral Sclerosis - ID: M21558 - Name: Neurodegenerative Diseases - Relevance: LOW - As Found: Unknown - ID: M12411 - Name: Neuromuscular Diseases - Relevance: LOW - As Found: Unknown - ID: M15915 - Name: Spinal Cord Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M28759 - Name: TDP-43 Proteinopathies - Relevance: LOW - As Found: Unknown - ID: M28747 - Name: Proteostasis Deficiencies - Relevance: LOW - As Found: Unknown - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown - ID: T4699 - Name: Primary Lateral Sclerosis - Relevance: LOW - As Found: Unknown - ID: T349 - Name: Amyotrophic Lateral Sclerosis - Relevance: HIGH - As Found: Amyotrophic Lateral Sclerosis ### Condition Browse Module - Meshes - ID: D000016472 - Term: Motor Neuron Disease - ID: D000000690 - Term: Amyotrophic Lateral Sclerosis ### Intervention Browse Module - Ancestors - ID: D000000975 - Term: Antioxidants - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000020011 - Term: Protective Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000002492 - Term: Central Nervous System Depressants ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Micro - Name: Micronutrients - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: HB - Name: Herbal and Botanical - Abbrev: Ot - Name: Other Dietary Supplements ### Intervention Browse Module - Browse Leaves - ID: M9789 - Name: Hormones - Relevance: LOW - As Found: Unknown - ID: M17201 - Name: Ubiquinone - Relevance: LOW - As Found: Unknown - ID: M271049 - Name: Coenzyme Q10 - Relevance: LOW - As Found: Unknown - ID: M11533 - Name: Melatonin - Relevance: HIGH - As Found: Profile - ID: M342247 - Name: Turmeric extract - Relevance: LOW - As Found: Unknown - ID: M5592 - Name: Carotenoids - Relevance: LOW - As Found: Unknown - ID: M273909 - Name: Idebenone - Relevance: LOW - As Found: Unknown - ID: M4292 - Name: Antioxidants - Relevance: LOW - As Found: Unknown - ID: M21869 - Name: Protective Agents - Relevance: LOW - As Found: Unknown - ID: T244 - Name: Orange - Relevance: LOW - As Found: Unknown - ID: T383 - Name: Coenzyme Q10 - Relevance: LOW - As Found: Unknown - ID: T410 - Name: Melatonin - Relevance: HIGH - As Found: Profile - ID: T229 - Name: Milk Thistle - Relevance: LOW - As Found: Unknown - ID: T319 - Name: Turmeric - Relevance: LOW - As Found: Unknown - ID: T312 - Name: Tea - Relevance: LOW - As Found: Unknown - ID: T407 - Name: Lutein - Relevance: LOW - As Found: Unknown - ID: T61 - Name: Ashwagandha - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000008550 - Term: Melatonin ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429046 **Brief Title:** Effect of Lidocaine Gel and Cold Lidocaine Gel on Pain in Patients Who Had Prostate Biopsy With Transrectal Ultrasound **Official Title:** Effect of Lidocaine Gel and Cold Lidocaine Gel Applied to the Rectal Area on Pain in Patients Who Had Prostate Biopsy With Transrectal Ultrasound: Randomized Controlled Study #### Organization Study ID Info **ID:** CukurovaUSFırat2 #### Organization **Class:** OTHER **Full Name:** Cukurova University ### Status Module #### Completion Date **Date:** 2023-09-12 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2022-07-29 **Type:** ACTUAL #### Start Date **Date:** 2020-01-02 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Study First Submit Date:** 2024-05-09 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Cukurova University #### Responsible Party **Investigator Affiliation:** Cukurova University **Investigator Full Name:** Sevda Fırat **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** Prostate cancer is one of the most common types of malignancy in men. Transrectal ultrasound-guided prostate biopsy (TRUSG-PBx) is considered the current gold standard method in the diagnosis of prostate cancer. Some patients experience serious discomfort during the procedure because the ultrasound probe is placed in the rectal area. Although no anesthetic or analgesic is used in some centers during the prostate biopsy procedure, in some centers lidocaine gel, cream or spray is applied before entering the rectal area, and lidocaine ampoule is injected during the procedure. However, most patients experience pain and discomfort due to the way the procedure is performed. Today, in addition to pharmacological methods, non-pharmacological methods are also used to control pain. Cold application has an important place among non-pharmacological methods. In this randomized controlled intervention study, the effect of cold lidocaine gel application on pain level in patients undergoing transrectal ultrasound-guided prostate biopsy (TRUSG-PBx) will be evaluated. In this study, it is thought that application of cold lidocaine gel will reduce the pain level of patients. The research will be conducted at the Urology Polyclinic of Çukurova University Faculty of Medicine Balcalı Practice and Research Hospital. The sample of the research; Ç.Ü.T.F. Volunteer patients who have undergone prostate biopsy at the Urology Polyclinic of Balcalı Practice and Research Hospital and meet the research criteria will be recruited. Patients consisting of 3 groups: control, experiment 1 (Lidocaine Gel) and experiment 2 (Cold Lidocaine Gel) will be determined by randomization. A power analysis was carried out by obtaining statistical support for the sample size. As a result of the sample calculation calculated with power with a confidence interval of 95%, beta value of 95% and alpha value of 0.05, a total of 114 patients will be included, 38 each in the control group, Lidocaine gel and Cold Lidocaine Gel groups. . Data will be collected with the "Personal Information Form" and "Pain Assessment Form". The data will be analyzed in the SPSS (Statistical Package for the Social Sciences) package program. In this context, in our study, the effect of lidocaine gel and cold lidocaine gel applied to the rectal area on the pain level in patients who underwent transrectal ultrasound-guided prostate biopsy will be evaluated and the effect of cold application on pain control will be compared. This result will make great contributions to patient benefit in terms of pain management. **Detailed Description:** Prostate cancer is one of the most common types of malignancy in men. According to GLOBOCAN (Global cancer statistics) 2020 data, the age-standardized incidence rate of prostate cancer varies between 11.3-37.5 per hundred thousand in the world, depending on the development level of the countries, and it is seen to be 42.5 per hundred thousand in our country. It ranks second after lung cancer in terms of incidence in men in our country and in the world. Prostate cancer screening aims to reduce mortality and morbidity by detecting prostate cancer at an early stage. Digital rectal examination (DRE), prostate specific antigen (PSA) value, transrectal ultrasonography (TRUS) and biopsy are used to diagnose prostate cancer. Ultrasound-guided prostate biopsy has been used since 1981 and is one of the most important urological diagnostic methods. Transrectal ultrasound-guided prostate biopsy (TRUSG-PBx) is currently considered the gold standard method in the diagnosis of prostate cancer. In the TRUSG-guided biopsy procedure, after the patients are placed in the left lateral or lithotomy position, the needle-guided rectal probe is inserted into the anal canal with the help of lubricating gel, and the prostate tissue is monitored under USG guidance and a biopsy is taken. The procedure takes approximately 20 minutes, and approximately 15 minutes pass during the entry and exit of the probe into the rectal area. In recent years, the importance of pain control has increased due to prostate biopsy being performed on younger patients, biopsies being taken from more quadrants, and repeated prostate biopsies. Due to severe pain, the rate of tolerance of the procedure by the patient decreases, and this may lead to a decrease in the number of biopsy samples taken from the planned quadrant and a decrease in cancer detection rates. Therefore, ensuring pain control and increasing patient tolerance in TRUSG-PBx is extremely important. Many different methods are used to reduce pain and discomfort. In recent studies, local anesthesia is used in transrectal ultrasound-guided prostate biopsies; Methods such as periprostatic nerve block (PPSB), lidocaine injection, intrarectal lidocaine gel, transperineal periprostatic block (TPPB with gel combination), low-dose spinal anesthesia and intravenous (IV) sedation application have been used and results have been reported showing that these methods increase the pain tolerance in the patient. One of the most important obstacles to the biopsy process is anal area pain. The pain felt during the biopsy occurs for 2 reasons: 1. Pain felt when the biopsy needle penetrates the prostate capsule and enters the stroma. 2. Pain caused by stretching of the anal sphincter as the transrectal ultrasound probe enters the anus (passing the ultrasound probe through the anus, advancing it into the rectum, and manipulating it within the rectum). For periprostatic nerve blockade before biopsy, penetration into the rectum with a rectal probe is required before anesthesia, and this first penetration is the main cause of the patients' complaints. Due to pain resulting from anal canal sensation during biopsy, intrarectal local anesthesia, which is highly absorbed through the rectal mucosa, is frequently used. Although the procedure is easy to perform and causes very low mortality, efforts to reduce the discomfort and pain that patients may feel lead to the development of new protocols for pre-procedure preparations and anesthesia and analgesia. Most patients who will undergo transrectal biopsy experience anxiety due to the possibility of the result being cancer, the psychological discomfort caused by the fact that the procedure will be performed rectally, and the procedure is painful for the patient. Nurses have an important and indispensable role in pain control and within the team. To reduce pain, nurses; They should inform patients about pain preventive approaches and pain control methods and give the message to patients that everything necessary has been done before painful procedures. Nurses should also apply non-pharmacological methods to reduce the consumption of analgesic drugs or increase their effect by providing adequate analgesia. The patient, whose anxiety decreases, will perceive the intensity and duration of pain as decreased as his sense of pain control will improve. Non-pharmacological methods are used alone or together with pharmacological methods in order to reduce the use of analgesics and at the same time improve the quality of life of the patient by relieving the patient's pain as much as possible. Cold application also has an important place among non-pharmacological methods. Cold application is effective in reducing pain, indirectly or directly. It indirectly reduces pain by eliminating edema, swelling and muscle spasm resulting from inflammation or trauma, and has a direct effect by changing the conduction properties of peripheral nerves. In this context, evidence-based studies should be examined and pharmacological and non-pharmacological methods that reduce pain should be used in patient care areas. A study in the literature showed that applying intrarectal lidocaine gel by massaging the anal area increases patient tolerance and provides balanced and adequate anesthesia at every stage of the biopsy. In another study in the literature, they compared the application of three intrarectal anesthesia methods along with periprostatic nerve block (periprostatic nerve block with intrarectal lidocaine gel, lidocaine cream and indomethacin suppository) during transrectal ultrasonography-guided prostate biopsy. They stated that intrarectal lidocaine cream application together with PPSB provided more effective pain control. In the literature, studies conducted to evaluate the effect of cold application on pain during removal of mediastinal and thorax tubes have observed that the application reduces pain, and it has been stated that applying cold to the entry point of the chest tubes reduces the pain and the amount of analgesic consumption during movement and coughing. As can be seen, various studies have been conducted to determine which anesthesia technique will reduce pain and to evaluate the rectal pain and sensitivity caused by the probe. However, it is still controversial which local anesthesia method is more suitable and will cause less pain. However, although there are many national and international studies on the subject in the literature, no experimental study has been found on the effect of cold lidocaine gel application on the pain level in patients who underwent transrectal ultrasound-guided prostate biopsy. The purpose of our research, which we planned in the light of this information, is to compare the effect of applying cold lidocaine gel to the rectal area on the pain level in patients who underwent transrectal ultrasound-guided prostate biopsy. ### Conditions Module **Conditions:** - Prostate Cancer XXX - TRANSRECTAL ULTRASOUND-GUIDED PROSTATE BIOPSY **Keywords:** - Cold application ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** This study was planned to compare the effects of lidocaine gel and cold lidocaine gel application to the rectal area on the pain level in patients who underwent TRUSG-guided prostate biopsy. ##### Masking Info **Masking:** NONE **Primary Purpose:** HEALTH_SERVICES_RESEARCH #### Enrollment Info **Count:** 120 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** For patients in the control group, "Personal Information Form" will be applied before the procedure and pain will be evaluated with "Numeric Pain Scale". NPS will be applied at the beginning of the procedure when the ultrasound probe is placed (NPS-1), 5 minutes after the procedure (NPS-2) and at the end of the procedure when the probe is removed (NPS-3). However, no treatment will be performed on control group patients. **Label:** CONTROL **Type:** NO_INTERVENTION #### Arm Group 2 **Description:** Data will be collected in two stages. To LG group patients, 20 ml lidocaine gel will be applied intrarectally (double application: 5cc to the perianal region, covering the anal sphincter, the remaining 15cc into the rectum) 5 minutes before the transrectal ultrasound probe is placed in the rectum. Patients in the LG group will be administered a "Personal Information Form" before the procedure, and their pain will be evaluated with the "Numeric Pain Scale". NPS will be applied at the beginning of the procedure when the ultrasound probe is placed (NPS-1), 5 minutes after the procedure (NPS-2) and at the end of the procedure when the probe is removed (NPS-3). **Intervention Names:** - Other: LIDOCAINE GEL **Label:** LIDOCAINE GEL (LG) **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Similarly, patients in the CLG group will be administered "Personal Information Form" before the procedure and pain will be evaluated with "Numeric Pain Scale". In CLG group patients, 20 ml of cold lidocaine gel kept in the refrigerator at +4 0C will be applied intrarectally (double application: 5cc to the perianal region, including the anal sphincter, the remaining 15cc into the rectum) 5 minutes before the transrectal ultrasound probe is placed into the rectum.NPS will be applied at the beginning of the procedure when the ultrasound probe is placed (NPS-1), 5 minutes after the procedure (NPS-2) and at the end of the procedure when the probe is removed (NPS-3). **Intervention Names:** - Other: COLD LIDOCAINE GEL **Label:** COLD LIDOCAINE GEL (CLG) **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - LIDOCAINE GEL (LG) **Description:** To LG group patients, 20 ml lidocaine gel will be applied intrarectally (double application: 5cc to the perianal region, covering the anal sphincter, the remaining 15cc into the rectum) 5 minutes before the transrectal ultrasound probe is placed in the rectum. **Name:** LIDOCAINE GEL **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - COLD LIDOCAINE GEL (CLG) **Description:** In CLG group patients, 20 ml of cold lidocaine gel kept in the refrigerator at +4 0C will be applied intrarectally (double application: 5cc to the perianal region, including the anal sphincter, the remaining 15cc into the rectum) 5 minutes before the transrectal ultrasound probe is placed into the rectum. **Name:** COLD LIDOCAINE GEL **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** The scale used in the first part of this form, which aims to evaluate pain severity, is the Numerical Pain Scale (NPS). On this scale, it starts with no pain (0) and reaches the level of unbearable pain (10). It was applied according to the determined measurement times of the patients \[At the beginning of the biopsy/while the ultrasound probe was being inserted (NPS) -1), During the biopsy/5 minutes after the ultrasound probe was placed (NPS-2), At the end of the biopsy/when the ultrasound probe was being removed (NPS-3)\]. **Measure:** Pain Evaluation Form **Time Frame:** The first 24 hours: NPS 1, 2, 3. #### Secondary Outcomes **Description:** This form, prepared by the researchers in line with the literature, aims to determine the individual characteristics of the patients (age, marital status, height/weight/body mass index, educational status, chronic disease status, previous rectal examination/procedure/biopsy, previous rectal 8 questions are included (e.g. pain status and level experienced during the examination/procedure/biopsy performed in the area). **Measure:** Personal Information Form **Time Frame:** Personal Information Form was applied before the transaction ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Being able to communicate effectively, * Being over 40 years old, * Being literate, * Volunteering to participate in the research. Exclusion Criteria: * Having a previous history of chronic pain, * Having alcohol and drug addiction, * Having bleeding diathesis and active urinary tract infection, * Having a cognitive disorder, neurological or psychiatric disease, * Having a disease in the anal and rectal area (wound, fistula, fissure, hemorrhoids, etc.). * Not agreeing to participate in the research. **Gender Based:** True **Gender Description:** PROSTATE **Healthy Volunteers:** True **Minimum Age:** 40 Years **Sex:** MALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Adana **Country:** Turkey **Facility:** Cukurova University **State:** Sariçam **Zip:** 01330 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000005834 - Term: Genital Neoplasms, Male - ID: D000014565 - Term: Urogenital Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000005832 - Term: Genital Diseases, Male - ID: D000091662 - Term: Genital Diseases - ID: D000091642 - Term: Urogenital Diseases - ID: D000011469 - Term: Prostatic Diseases - ID: D000052801 - Term: Male Urogenital Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC01 - Name: Infections - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases ### Condition Browse Module - Browse Leaves - ID: M14335 - Name: Prostatic Neoplasms - Relevance: HIGH - As Found: Prostate Cancer - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M14978 - Name: Respiratory Tract Infections - Relevance: LOW - As Found: Unknown - ID: M8946 - Name: Genital Neoplasms, Male - Relevance: LOW - As Found: Unknown - ID: M17315 - Name: Urogenital Neoplasms - Relevance: LOW - As Found: Unknown - ID: M2876 - Name: Genital Diseases - Relevance: LOW - As Found: Unknown - ID: M8944 - Name: Genital Diseases, Male - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M14333 - Name: Prostatic Diseases - Relevance: LOW - As Found: Unknown - ID: M27095 - Name: Male Urogenital Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000011471 - Term: Prostatic Neoplasms ### Intervention Browse Module - Ancestors - ID: D000000779 - Term: Anesthetics, Local - ID: D000000777 - Term: Anesthetics - ID: D000002492 - Term: Central Nervous System Depressants - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000018689 - Term: Sensory System Agents - ID: D000018373 - Term: Peripheral Nervous System Agents - ID: D000000889 - Term: Anti-Arrhythmia Agents - ID: D000061567 - Term: Voltage-Gated Sodium Channel Blockers - ID: D000026941 - Term: Sodium Channel Blockers - ID: D000049990 - Term: Membrane Transport Modulators - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: AnArAg - Name: Anti-Arrhythmia Agents - Abbrev: ChanBlk - Name: Channel Blockers - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M11014 - Name: Lidocaine - Relevance: HIGH - As Found: Solution - ID: M4107 - Name: Anesthetics - Relevance: LOW - As Found: Unknown - ID: M4109 - Name: Anesthetics, Local - Relevance: LOW - As Found: Unknown - ID: M4213 - Name: Anti-Arrhythmia Agents - Relevance: LOW - As Found: Unknown - ID: M23177 - Name: Sodium Channel Blockers - Relevance: LOW - As Found: Unknown - ID: M30025 - Name: Diuretics, Potassium Sparing - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000008012 - Term: Lidocaine ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429033 **Acronym:** PEP **Brief Title:** Purified Exosome Product (PEP) Injected Into the Hypodermis **Official Title:** A Prospective, Within-Subject Controlled Study to Evaluate the Safety and Histological Profile of Purified Exosome Product Into the Hypodermis of Healthy Adults #### Organization Study ID Info **ID:** PEP-23-002 #### Organization **Class:** OTHER **Full Name:** Clinical Testing of Beverly Hills ### Status Module #### Completion Date **Date:** 2025-12-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-28 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-24 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2025-09-30 **Type:** ESTIMATED #### Start Date **Date:** 2024-07-01 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Study First Submit Date:** 2024-05-15 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Clinical Testing of Beverly Hills #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Is US Export:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** This clinical trial aims to learn if Purified Exosome Product (PEP) is safe and tolerable when injected into the hypodermis of healthy adults. The main questions this study aims to answer are: Is PEP safe and tolerable when injected into the hypodermis of healthy adults? Are there signals of Collagen I/II and Elastin biostimulation? Subjects will serve as their own control and researchers will compare PEP to Control to see if PEP is safe. **Detailed Description:** This is a prospective, non-randomized, within-subject, controlled, single center, open-label study. Up to 9 healthy adult participants with planned elective body reduction surgery to remove excess skin on the abdomen in ≥ 12 to ≤ 18 weeks will be enrolled and injected with a single dose of PEP Drug Product reconstituted in Lactated Ringers (USP) solution in a defined area of the abdominal hypodermis. Similar tissue from the participant's contralateral side of the abdomen will serve as the control. Excised tissue will be harvested and analyzed for histological findings (collagen, pre-collagen, elastin) as an exploratory endpoint. The primary goal of this investigator-initiated study is to determine safety of subcutaneous PEP Drug Product when reconstituted in Lactated Ringers solution. Safety data will be collected with frequent monitoring for adverse events, laboratory testing, vital signs, and ECGs. Note: The decision to undergo abdominoplasty will be made outside of this study and data/safety in the plastic surgery procedure for abdominoplasty, other than informed consent, will not be a collected as a part of this study. ### Conditions Module **Conditions:** - Safety ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SEQUENTIAL ##### Masking Info **Masking:** NONE **Primary Purpose:** OTHER #### Enrollment Info **Count:** 9 **Type:** ESTIMATED **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** A single dose of Purified Exosome Product in Lactated Ringers at doses of 1 vial (75 mg) (Low Dose/Cohort 1) or 2 vials (150 mg) (Target Dose/Cohort 2) will be injected intradermally into the hypodermis of a 5 cm by 10 cm section of abdomen (to the right of the umbilicus) that is planned for removal during abdominoplasty surgery. The solution will be injected into the hypodermis in approximately 50 each 0.2 mL boluses, approximately 1cm apart. **Intervention Names:** - Drug: Purified Exosome Product (PEP) **Label:** Treatment Group **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Treatment Group **Description:** Injection of PEP into hypodermis of abdomen **Name:** Purified Exosome Product (PEP) **Type:** DRUG ### Outcomes Module #### Other Outcomes **Description:** Histology evaluation **Measure:** Histopathology **Time Frame:** 6-months #### Primary Outcomes **Description:** The number of subjects with acute dose-limiting toxicities **Measure:** Safety: Dose limiting toxicities **Time Frame:** 14-days **Description:** The maximum tolerated dose determined by testing increasing doses of PEP **Measure:** Maximum Tolerated Dose **Time Frame:** 14-days #### Secondary Outcomes **Description:** The number of subjects experiencing serious adverse events, as adjudicated by the Data Safety Monitoring Board (DSMB) **Measure:** Serious Adverse Events **Time Frame:** 14 days **Description:** The number of subjects experiencing adverse events **Measure:** Adverse Events **Time Frame:** 26-weeks **Description:** The number of CTRs experienced by the subject, as recorded in the diary **Measure:** Common Treatment Responses (CTRs) **Time Frame:** 14-days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Adult participants aged 18-65 (inclusive) * Capacity to sign informed consent. * Planned elective body reduction surgery to remove excess skin on the abdomen in ≥ 3 to ≤ 5 months * Participant is judged, by the clinical investigator, to be healthy as evidenced by lack of clinically significant abnormal findings on medical history, physical examination, vital signs, and clinical laboratory tests. * Participant should be willing to comply with the study procedure and schedule, including the follow up visit, and will refrain from using any other aesthetic treatment methods (laser devices, topical prescriptions, or other known hair growth treatments) in the treatment area during the entire study period. * Females of childbearing potential must be using an approved method of birth control for the past month and during the entire study period. Participants who can become pregnant will undergo a pregnancy test prior to treatment. Exclusion Criteria: * Participants with clinically abnormal hematology, serum chemistries, or screening laboratory results as reviewed by the clinical investigator. * Known history of MRSA (methicillin-resistant staphylococcus aureus). * Known history of COVID-19 infection in past 6 months. * COVID vaccine or booster dose within past 12 weeks. * Participants who are positive for hepatitis B surface antigen (HbsAg), hepatitis C antibody, or HIV. * History of antibiotic use in past 12 weeks. * Major surgery in past 3 months. * If taking hormone replacement therapy or hormones for birth control, dose must be stable for at least 6 months prior to study entry. * Current or regular use of corticosteroids during the previous 4 weeks, excluding inhaled or topical steroids outside of the planned treatment area. * Known sensitivity/allergy to study product ingredients. * Pregnancy and nursing or lactating. * Sexually active women of childbearing potential who are unwilling to use approved contraception method for three months after receiving dose of investigational drug. * Impaired immune system due to immunosuppressive diseases such as AIDS and HIV or use of immunosuppressive medications. * Clinically significant cardiovascular, pulmonary, renal, endocrine, hepatic, neurological, psychiatric, immunological, gastrointestinal, hematological, history of any malignancies or metabolic disease that is, in the opinion of the investigator, not stabilized or may otherwise impact the results of the study. * Participants with hepatic impairment * Participants with poorly controlled diabetes mellitus (HbA1C ≥ 8%). * Any active condition in the treatment area, such as sores, psoriasis, eczema, and rash. * History of skin disorders, keloids, abnormal wound healing, as well as very dry and fragile skin. * Any surgery or treatment such as laser or chemicals in the treatment area within 6 months prior to treatment * Any medical condition that in the opinion of the investigator, such condition would compromise the safety of the participant or quality of the study data. * Current, or past participation in a clinical trial within the past 30 days. **Healthy Volunteers:** True **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Mary Hayes **Phone:** 818-616-3880 **Role:** CONTACT ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Intervention Browse Module - Browse Branches - Abbrev: PhSol - Name: Pharmaceutical Solutions - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M21860 - Name: Pharmaceutical Solutions - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429020 **Brief Title:** Sonography for COVID-19 Vaccines Related Reactive Lymphadenopathy **Official Title:** Sonography for COVID-19 Vaccines Related Reactive Lymphadenopathy: A Retrospective Study #### Organization Study ID Info **ID:** CMMC11201-010 #### Organization **Class:** OTHER **Full Name:** Chimei Medical Center ### Status Module #### Completion Date **Date:** 2023-12-31 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2023-12-31 **Type:** ACTUAL #### Start Date **Date:** 2023-01-01 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Study First Submit Date:** 2024-05-13 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Chimei Medical Center #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** This study aimed to provide vast clinical information to facilitate breast sonographic examination for participants who underwent recent SARS-CoV-2 vaccination. Among different SARS-CoV-2 vaccines in the Asian Taiwanese population, reactive axillary lymphadenopathy was investigated through breast sonographic findings and clinical data analysis. The sample included participants with recent vaccinations by different brands approved in Taiwan. **Detailed Description:** Study Design and Sample The retrospective study included female patients who underwent breast sonography in the radiology department of Chi Mei Medical Center between July 2021 and March 2022. The patients' breast cancer history and COVID-19 vaccination history were collected and analyzed. Analysis of Breast Sonography Lymphadenopathy is defined as an enlarged lymph node with cortical thickening \>3 mm, either concentric or eccentric, with or without effacement of fatty hilum, or in-creased non-hilar vascularity on color or power Doppler. The positive axillary lymph node findings were correlated by confirming a link to SARS-CoV-2 vaccination history within 90 days in the ipsilateral arm. Statistical Analysis All statistical analyses were performed using the R Stats package. Descriptive summaries were reported as mean ± standard deviation for continuous variables and percentages for categorical variables. For non-parametric variables, median with interquartile range and Mann-Whitney U test were used. Statistical significance was set at a p-value \<0.05. ### Conditions Module **Conditions:** - Reactive Axillary Lymphadenopathy for SARS-CoV-2 Vaccines in the Asian Taiwanese Population **Keywords:** - Breast Neoplasms - covid-19 vaccine - lymphadenopathy ### Design Module #### Design Info **Observational Model:** CASE_CONTROL **Time Perspective:** RETROSPECTIVE #### Enrollment Info **Count:** 1089 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** non SARS-COV-2 vaccinated group **Label:** control group #### Arm Group 2 **Description:** SARS-COV-2 vaccinated group **Intervention Names:** - Biological: the AstraZeneca ChAdOx1 (AZ) vaccine, Moderna mRNA-1273 (Moderna) vaccine, and Pfizer-BioNTech BNT162b2 (BNT) vaccine. **Label:** vaccinated group ### Interventions #### Intervention 1 **Arm Group Labels:** - vaccinated group **Description:** record the condition of vaccination **Name:** the AstraZeneca ChAdOx1 (AZ) vaccine, Moderna mRNA-1273 (Moderna) vaccine, and Pfizer-BioNTech BNT162b2 (BNT) vaccine. **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Measure:** Presentation of axillary lymphadenopathy in sonographic examination **Time Frame:** through study completion, an average of 1 year ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * female patients receiving breast sonography Exclusion Criteria: * receive Covid 19 vaccine other than AZ, BNT, Moderna * Ongoing primary breast malignancy * History of malignancy other than primary breast malignancy **Healthy Volunteers:** True **Maximum Age:** 80 Years **Minimum Age:** 20 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Patients who underwent breast sonography in the radiology department of Chi Mei Medical Center between July 2021 and March 2022. ### Contacts Locations Module #### Locations **Location 1:** **City:** Tainan City **Country:** Taiwan **Facility:** ChiMei Medical Center **Zip:** 710402 #### Overall Officials **Official 1:** **Affiliation:** ChiMei Medical Center, Taiwan, R.O.C. **Name:** Pin Chi Huang **Role:** STUDY_CHAIR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000011024 - Term: Pneumonia, Viral - ID: D000011014 - Term: Pneumonia - ID: D000012141 - Term: Respiratory Tract Infections - ID: D000007239 - Term: Infections - ID: D000014777 - Term: Virus Diseases - ID: D000018352 - Term: Coronavirus Infections - ID: D000003333 - Term: Coronaviridae Infections - ID: D000030341 - Term: Nidovirales Infections - ID: D000012327 - Term: RNA Virus Infections - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases - ID: D000008206 - Term: Lymphatic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC01 - Name: Infections - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M5220 - Name: Breast Neoplasms - Relevance: LOW - As Found: Unknown - ID: M2561 - Name: COVID-19 - Relevance: HIGH - As Found: COVID-19 - ID: M994 - Name: Lymphadenopathy - Relevance: HIGH - As Found: Lymphadenopathy - ID: M13904 - Name: Pneumonia - Relevance: LOW - As Found: Unknown - ID: M13914 - Name: Pneumonia, Viral - Relevance: LOW - As Found: Unknown - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M14978 - Name: Respiratory Tract Infections - Relevance: LOW - As Found: Unknown - ID: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M20490 - Name: Coronavirus Infections - Relevance: LOW - As Found: Unknown - ID: M6555 - Name: Coronaviridae Infections - Relevance: LOW - As Found: Unknown - ID: M23685 - Name: Nidovirales Infections - Relevance: LOW - As Found: Unknown - ID: M15149 - Name: RNA Virus Infections - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: M11203 - Name: Lymphatic Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000086382 - Term: COVID-19 - ID: D000072281 - Term: Lymphadenopathy ### Intervention Browse Module - Ancestors - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M17360 - Name: Vaccines - Relevance: HIGH - As Found: Other - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000014612 - Term: Vaccines ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06429007 **Brief Title:** A Safety and Feasibility Trial Protocol of Metformin in Infants After Perinatal Brain Injury **Official Title:** A Safety and Feasibility Trial Protocol of Metformin in Infants After Perinatal Brain Injury #### Organization Study ID Info **ID:** IRB-P00048370 #### Organization **Class:** OTHER **Full Name:** Boston Children's Hospital ### Status Module #### Completion Date **Date:** 2027-10-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2026-10-01 **Type:** ESTIMATED #### Start Date **Date:** 2024-10-01 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Study First Submit Date:** 2024-05-07 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Boston Children's Hospital #### Responsible Party **Investigator Affiliation:** Boston Children's Hospital **Investigator Full Name:** Martha Sola-Visner **Investigator Title:** Research Director, Department of Newborn Medicine **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Is US Export:** True **Oversight Has DMC:** True ### Description Module **Brief Summary:** Infants with hypoxic-ischemic encephalopathy (HIE) are at high risk for neurodevelopmental impairment, despite current standards of care. Adjunctive treatments to promote brain repair are needed. The antidiabetic drug metformin has recently been recognized as a neurorestorative agent, but, to date, has not been used in infants. Herein, the investigator describes a clinical trial with the aim of demonstrating the safety and feasibility of metformin use to improve neurodevelopmental outcomes in infants with HIE. ### Conditions Module **Conditions:** - Hypoxic-Ischemic Encephalopathy - HIE - Neurodevelopment - Infant Development **Keywords:** - HIE - metformin - Hypoxic-Ischemic Encephalopathy - Pharmacokinetic modeling - Neonates - Brain Injury ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 30 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants will complete a pre-study visit with baseline bloodwork including a complete blood count (CBC), liver and renal function, basic chemistry, glucose, and lactate. At this visit, parents will be taught how to administer metformin and given a 6-week supply of metformin at 50% of the target dose to minimize potential gastrointestinal upset. Parents will be educated on adverse effects and receive a diary to log dose administration and noted side effects. After six weeks, participants will return for a study visit with repeat labs. Bloodwork at this visit will include plasma metformin levels for measurement of pharmacokinetics. Study staff will also review diary completion for adverse effects and to ensure there have been no missed doses. Parents will then receive a 6-week supply of metformin 25mg/kg for 6 weeks. A final study visit will then occur following 12-weeks of metformin therapy, with repeat labs including plasma metformin levels. **Intervention Names:** - Drug: Metformin **Label:** Metformin Intervention **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Metformin Intervention **Description:** Infants in the study will receive 50% of the target dose (12.5mg/kg) for the first 6 weeks of participation. At the 6 week visit, the patient will be assessed and if found still eligible, will receive the full dose (25mg/kg) for the remaining 6 weeks of participation. **Name:** Metformin **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** A renal function panel (chem 10 with renal function) will be performed prior to the initiation of therapy and at all subsequent study visits. **Measure:** Safety profile of kidney function **Time Frame:** 12 weeks **Description:** A liver function test (LFT) will be performed prior to the initiation of therapy and at all subsequent study visits. **Measure:** Safety profile of liver function **Time Frame:** 12 weeks **Description:** To assess feasibility, the number of eligible patients will be compared to the number of patients who consent to participate in the study. **Measure:** Recruitment feasibility **Time Frame:** 12 weeks #### Secondary Outcomes **Description:** Plasma metformin levels will be analyzed by investigators with whole blood obtained at study visits. **Measure:** Validity of neonatal model of metformin pharmacokinetics **Time Frame:** 12 weeks **Description:** Parents/caregivers will be sent a survey that utilizes a 5 point Likert scale to assess key factors that prevented or encouraged participation. **Measure:** Stakeholder Satisfaction **Time Frame:** 12 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Infants born \> 35 weeks' gestational age AND * Received therapeutic hypothermia for clinically diagnosed HIE Exclusion Criteria: * Infants with known genetic or chromosomal disorders * Infants with a liver or kidney disease that may affect drug metabolism * Maternal metformin use while actively breastfeeding * Infant weight is below the 10th percentile (as defined by World Health Organization) at time of study drug initiation. **Maximum Age:** 6 Months **Minimum Age:** 3 Months **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Vanessa Young, MS, RN **Phone:** 617-355-8330 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Kate Eident, BS **Phone:** 617-355-2184 **Role:** CONTACT #### Overall Officials **Official 1:** **Affiliation:** Boston Children's Hospital **Name:** Martha Sola-Visner, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000006259 - Term: Craniocerebral Trauma - ID: D000020196 - Term: Trauma, Nervous System - ID: D000014947 - Term: Wounds and Injuries - ID: D000000860 - Term: Hypoxia - ID: D000012818 - Term: Signs and Symptoms, Respiratory - ID: D000002561 - Term: Cerebrovascular Disorders - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000002534 - Term: Hypoxia, Brain ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC26 - Name: Wounds and Injuries ### Condition Browse Module - Browse Leaves - ID: M5794 - Name: Brain Ischemia - Relevance: HIGH - As Found: Ischemic Encephalopathy - ID: M10543 - Name: Ischemia - Relevance: LOW - As Found: Unknown - ID: M4185 - Name: Hypoxia - Relevance: LOW - As Found: Unknown - ID: M5207 - Name: Brain Injuries - Relevance: HIGH - As Found: Brain Injury - ID: M5204 - Name: Brain Diseases - Relevance: HIGH - As Found: Encephalopathy - ID: M22660 - Name: Hypoxia-Ischemia, Brain - Relevance: HIGH - As Found: Hypoxic Ischemic Encephalopathy - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown - ID: M9349 - Name: Craniocerebral Trauma - Relevance: LOW - As Found: Unknown - ID: M22023 - Name: Trauma, Nervous System - Relevance: LOW - As Found: Unknown - ID: M15623 - Name: Signs and Symptoms, Respiratory - Relevance: LOW - As Found: Unknown - ID: M5810 - Name: Cerebrovascular Disorders - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: M5783 - Name: Hypoxia, Brain - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001930 - Term: Brain Injuries - ID: D000001927 - Term: Brain Diseases - ID: D000002545 - Term: Brain Ischemia - ID: D000020925 - Term: Hypoxia-Ischemia, Brain ### Intervention Browse Module - Ancestors - ID: D000007004 - Term: Hypoglycemic Agents - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: Hypo - Name: Hypoglycemic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Hemat - Name: Hematinics ### Intervention Browse Module - Browse Leaves - ID: M11667 - Name: Metformin - Relevance: HIGH - As Found: Assessment - ID: M11110 - Name: Liver Extracts - Relevance: LOW - As Found: Unknown - ID: M10054 - Name: Hypoglycemic Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000008687 - Term: Metformin ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06428994 **Brief Title:** Risk for Subsequent Osteoradionecrosis in A Transferred Fibula Flap in Head and Neck Cancer Patients Undergoing Segmental Mandibulectomy: a Cohort Study **Official Title:** Risk for Subsequent Osteoradionecrosis in A Transferred Fibula Flap in Head and Neck Cancer Patients Undergoing Segmental Mandibulectomy: a Cohort Study #### Organization Study ID Info **ID:** No. 201800172B0 #### Organization **Class:** OTHER **Full Name:** Chang Gung Memorial Hospital ### Status Module #### Completion Date **Date:** 2022-02-28 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2022-02-28 **Type:** ACTUAL #### Start Date **Date:** 2019-03-01 **Type:** ACTUAL **Status Verified Date:** 2018-02 #### Study First Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Study First Submit Date:** 2024-05-12 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Chang Gung Memorial Hospital #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** A retrospective analysis of 329 patients at one single institution between January 2014 and December 2019 who underwent free fibula flap reconstruction was conducted. A variety of clinicopathological postoperative parameters were identified and assessed. **Detailed Description:** The study was conducted as a monocentric, retrospective study. Patients who underwent a mandibular reconstruction with a free fibula flap due to head and neck cancer through January 2014 to December 2019 at one single institution in Taiwan were identified. All charts including surgical records, progress notes, nursing records, clinic notes, imaging study after surgery were reviewed. Data extraction was performed for the following variables: Patient demographics, primary diagnosis, cancer location and staging, treatment prior to index surgery, postoperative hemoglobin and albumin, operating time, flap type, mandibular defect length, type of the defect according to Jewer's classification, ischemia time, number of fibula segments, plate type, re-exploration, time of hospitalization, postoperative radiotherapy and/or chemotherapy, ORN cases, identification time of ORN and management for ORN. The patients were then organized into two groups: ORN and non-ORN. This research was approved by the Institutional Review Board of our hospital (No. 201800172B0), which was available until 2022/02/28. The investigators completed data analysis before 2022/02/28 and then initiated manuscript preparing. ### Conditions Module **Conditions:** - Head and Neck Cancer - Fibula Flap - Osteoradionecrosis - Mandibulectomy ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** RETROSPECTIVE #### Enrollment Info **Count:** 580 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** ORN in this study is defined as exposed irradiated bone tissue that fails to heal over a period of three months without residual or recurrent tumors. **Intervention Names:** - Radiation: Radiotherapy **Label:** ORN #### Arm Group 2 **Description:** Patients without ORN. **Label:** non-ORN ### Interventions #### Intervention 1 **Arm Group Labels:** - ORN **Description:** Post-operative radiotherapy for head and neck cancer **Name:** Radiotherapy **Type:** RADIATION ### Outcomes Module #### Primary Outcomes **Description:** The incidence of osteoradionecrosis in patients who received free fibula flap reconstruction **Measure:** The incidence on development osteoradionecrosis(ORN) in free fibula flaps **Time Frame:** Up to 7 years postoperatively ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients who underwent a mandibular reconstruction with a free fibula flap due to head and neck cancer through January 2014 to December 2019. Exclusion Criteria: * Cases with incomplete medical records. * Patients who did not attend at least 6 months of follow ups. **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Between January 2014 and December 2019, 580 patients received free fibula flap mandibular reconstruction, with 374 of them attributed to head and neck cancer reconstruction. Cases with incomplete medical records were excluded (n = 9). Additionally, patients who did not attend at least 6 months of follow-up were also excluded (n = 36). Finally, 329 patients including 309 males and 20 females met the inclusion criteria of this study. ### Contacts Locations Module #### Locations **Location 1:** **City:** Taoyuan **Country:** Taiwan **Facility:** Angela Chien-Yu Chen **Zip:** 333 ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000011832 - Term: Radiation Injuries - ID: D000014947 - Term: Wounds and Injuries ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions - Abbrev: BC26 - Name: Wounds and Injuries ### Condition Browse Module - Browse Leaves - ID: M9348 - Name: Head and Neck Neoplasms - Relevance: HIGH - As Found: Head and Neck Cancer - ID: M12948 - Name: Osteoradionecrosis - Relevance: HIGH - As Found: Osteoradionecrosis - ID: M14679 - Name: Radiation Injuries - Relevance: LOW - As Found: Unknown - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006258 - Term: Head and Neck Neoplasms - ID: D000010025 - Term: Osteoradionecrosis ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06428981 **Brief Title:** Surgical Intervention on the Body-mind-spirit of Patients With Cervical Spine Surgery **Official Title:** (Holistic Health Care) Influence of Surgical Intervention on the Body-mind-spirit of Patients Undergoing Cervical Spine Surgery #### Organization Study ID Info **ID:** 202200381B0 #### Organization **Class:** OTHER **Full Name:** Chang Gung Memorial Hospital ### Status Module #### Completion Date **Date:** 2024-02-26 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2023-12-30 **Type:** ACTUAL #### Start Date **Date:** 2022-08-02 **Type:** ACTUAL **Status Verified Date:** 2022-04 #### Study First Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Study First Submit Date:** 2024-05-15 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Chang Gung Memorial Hospital #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** The study aimed to evaluate if surgical intervention in patients with degenerative cervical diseases improves quality of life (QOL), lowers pain-induced mental impairment, improves psychologic health, and promotes spiritual well-being. **Detailed Description:** Degenerative cervical disease induces cervical radiculopathy and myelopathy, which have a significant impact on the patients' health. The study aimed to evaluate if surgical intervention in patients with degenerative cervical diseases improves quality of life (QOL), lowers pain-induced mental impairment, improves psychologic health, and promotes spiritual well-being. ### Conditions Module **Conditions:** - Cervical Spine Degeneration ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** HEALTH_SERVICES_RESEARCH #### Enrollment Info **Count:** 35 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The inclusion criteria consisted of patients over the age of 20 who were diagnosed with degenerative cervical diseases, including herniation of the intervertebral disc, ossification of the posterior longitudinal ligament, and spinal stenosis, resulting in cervical radiculopathy, or degenerative cervical myelopathy, and were scheduled to undergo anterior discectomy with fusion surgery. **Intervention Names:** - Other: degenerative cervical diseases **Label:** spine surgery **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - spine surgery **Description:** Including herniation of the intervertebral disc, ossification of the posterior longitudinal ligament, and spinal stenosis, resulting in cervical radiculopathy, or degenerative cervical myelopathy, and were scheduled to undergo anterior discectomy with fusion surgery. **Name:** degenerative cervical diseases **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** The outcomes were assessed using the 36-item Short Form Health Survey Quality of Life Scale (SF-36) before surgery. **Measure:** Quality of life, mental health, pain relief, and spiritual health before surgery **Time Frame:** Before surgery **Description:** The outcomes were assessed using the Patient Health Questionnaire-9 (PHQ9) scale before surgery. **Measure:** Quality of life, mental health, pain relief, and spiritual health before surgery **Time Frame:** Before surgery **Description:** The outcomes were assessed using the Pain Disability Questionnaire (PDQ) scale before surgery. **Measure:** Quality of life, mental health, pain relief, and spiritual health before surgery **Time Frame:** Before surgery **Description:** The outcomes were assessed using the Holistic Well-being Scale (HWS) scale before surgery. **Measure:** Quality of life, mental health, pain relief, and spiritual health before surgery **Time Frame:** Before surgery **Description:** The outcomes were assessed using the 36-item Short Form Health Survey Quality of Life Scale (SF-36) six months after surgery. **Measure:** Quality of life, mental health, pain relief, and spiritual health after surgery **Time Frame:** six months after surgery **Description:** The outcomes were assessed using the Patient Health Questionnaire-9 (PHQ9) scale six months after surgery. **Measure:** Quality of life, mental health, pain relief, and spiritual health after surgery **Time Frame:** six months after surgery **Description:** The outcomes were assessed using the Pain Disability Questionnaire (PDQ) scale six months after surgery. **Measure:** Quality of life, mental health, pain relief, and spiritual health after surgery **Time Frame:** six months after surgery **Description:** The outcomes were assessed using the Holistic Well-being Scale (HWS) scale six months after surgery. **Measure:** Quality of life, mental health, pain relief, and spiritual health after surgery **Time Frame:** six months after surgery ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients over the age of 20 who were diagnosed with degenerative cervical diseases, including herniation of the intervertebral disc, ossification of the posterior longitudinal ligament, and spinal stenosis, resulting in cervical radiculopathy, or degenerative cervical myelopathy, and were scheduled to undergo anterior discectomy with fusion surgery. Exclusion Criteria: * Patients who were unable to attend follow-up visits or complete the questionnaires, and those patients who expressed doubts or were unable to provide satisfactory responses regarding the trial. **Maximum Age:** 100 Years **Minimum Age:** 20 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Kaohsiung **Country:** Taiwan **Facility:** Kaohsiung Chang Gung Memorial Hospital **Zip:** 83301 ## Derived Section ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06428968 **Brief Title:** Investigating the Insulin Resistance in Individuals With Type 2 Diabetes **Official Title:** Investigating the Central and Peripheral Insulin Resistance in Individuals With Type 2 Diabetes #### Organization Study ID Info **ID:** T2DM2024 #### Organization **Class:** OTHER **Full Name:** Central South University ### Status Module #### Completion Date **Date:** 2025-06-30 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2024-12-31 **Type:** ESTIMATED #### Start Date **Date:** 2024-05-15 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Study First Submit Date:** 2024-05-07 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Central South University #### Responsible Party **Investigator Affiliation:** Central South University **Investigator Full Name:** Renrong Wu **Investigator Title:** Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Numerous studies have provided evidence of a correlation between Type 2 Diabetes Mellitus (T2DM) and cognitive dysfunction, specifically in the realms of complex attention, information processing, and executive function. These impairments have been observed in middle-aged and elderly individuals with T2DM, with longer diabetes duration, suboptimal glycemic control, and the presence of diabetic complications being contributing factors. Recent research in young adults and adolescents diagnosed with T2DM has revealed cognitive and brain structural alterations in this growing demographic, suggesting that early disease mechanisms, rather than solely vascular and age-related neurodegeneration, contribute to pathogenesis. However, there remains uncertainty regarding the interplay between central and peripheral insulin resistance and its impact on cognitive dysfunction in individuals with T2DM. This study aims to investigate central insulin resistance in T2DM, elucidating its association with peripheral insulin resistance and the effects on cognitive impairments. **Detailed Description:** Participants screened through inclusion and exclusion criteria will accept cross-sectional evaluation. The information of demographic data, medical history, previous and current medication regimen, details of complications, and family history regarding metabolic diseases will be collected. The assessments includes physical examination, anthropometry, blood test(blood routine, liver function, renal function, blood lipids, fasting blood glucose, serum insulin，thyroid function and glycosylated hemoglobin A 1c), MRI scan( High-resolution T1-weighted Anatomical Images, Diffusion Tensor Imaging, Resting-state functional MRI and Arterial Spin Labeling) and psychiatry scales(Hamilton Depression Scale, Young Mania Rating Scale and Self-reporting Inventory-90); cognitive function will be assessed by the Measurement and Treatment Research to Improve Cognition in Schizophrenia(MATRICS) Consensus Cognitive Battery; biological samples also will be collected and stored to explore related mechanisms. ### Conditions Module **Conditions:** - Type 2 Diabetes **Keywords:** - Insulin resistance - Cognitive impairments ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** SCREENING #### Enrollment Info **Count:** 30 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Individual with type 2 diabetes **Intervention Names:** - Drug: 160 units nasal insulin spray **Label:** Individual with type 2 diabetes **Type:** EXPERIMENTAL #### Arm Group 2 **Intervention Names:** - Drug: 160 units nasal insulin spray **Label:** Healthy volunteers **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Healthy volunteers - Individual with type 2 diabetes **Description:** Initially, a series of MRI scans, including high-resolution T1-weighted anatomical images, diffusion tensor imaging, resting-state functional MRI, and arterial spin labeling, will be conducted. Subsequently, 160 units of nasal insulin spray will be administered, followed by a second round of MRI scans after a 30-minute interval, encompassing high-resolution T1-weighted anatomical images, resting-state functional MRI, and arterial spin labeling. **Name:** 160 units nasal insulin spray **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Whole brain cerebral blood flow (CBF) will be recorded by arterial spin labeling (ASL). the changes in CBF (c-CBF) before and after the application of 160 units nasal insulin spray of interventional participants will be calculated. The c-CBF is an index of central insulin response. **Measure:** The difference of changes of brain cerebral blood flow by arterial spin labeling between type 2 diabetes and healthy volunteers. **Time Frame:** Baseline **Description:** Phosphorylated insulin receptor substrate 1 and its downstream mediators represent the state of neuronal insulin resistance, whose improvement means better insulin signaling. For individuals with type 2 diabetes mellitus and healthy volunteers, blood samples will be collected and stored at -80℃ at baseline. The NEVs isolation and biomarker measurements will be processed uniformly, and the difference of the level of insulin signaling between two groups will be used for exploring underlying mechanism of disease. **Measure:** The difference of the level of insulin signaling in Extracellular Vesicles of neuronal origin isolated from blood between type 2 diabetes and healthy volunteers. **Time Frame:** Baseline **Description:** The cognitive function of interventional participants will be assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery. Evaluator convert raw scores to scale scores, then to normalized T scores. T scores of seven domains and composite score are further calculated. The difference of T scores between two groups will be used for evaluating cognitive function. (higher score means better function). **Measure:** The difference of the score of the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery between type 2 diabetes and healthy volunteers. **Time Frame:** Baseline **Description:** The resting-state functional MRI(fMRI) will be conducted at fasting state and after the application of 160 units nasal insulin spray. For every participants, the changes in fMRI (c-fMRI) under the application of nasal insulin spray will be analysed. The c-fMRI between type 2 diabetes and healthy volunteers may reflect the underlying mechanism of disease. **Measure:** The difference of c-fMRI between type 2 diabetes and healthy volunteers. **Time Frame:** Baseline #### Secondary Outcomes **Description:** Diffusion Tensor Imaging (DTI) will be performed using diffusion-weighted echo planar imaging sequences. The analysis of DTI will be conducted to investigate the difference of brain structure and morphology between type 2 diabetes and healthy volunteers. **Measure:** The difference of Diffusion Tensor Imaging scanned by MRI between type 2 diabetes and healthy volunteers **Time Frame:** Baseline ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Meeting the diagnostic criteria for Type 2 diabetes: typical symptoms of diabetes plus random blood glucose level of ≥11.1 mmol/l, or fasting blood glucose level of ≥7.0 mmol/l, or 2-hour post-OGTT (Oral Glucose Tolerance Test) blood glucose level of ≥11.1 mmol/l, or HbA1c level of ≥6.5%; for those without typical symptoms of diabetes, re-examination on a different day is required for confirmation. Exclusion Criteria: * Having history of substance dependence or abuse or whose symptoms are caused by diagnosable mental disorders; * Having history of traumatic brain injury, seizures or other known neurological or organic diseases of the central nervous system; * Having current suicidal or homicidal thoughts or any safety concern by research staff that cannot be manage in an inpatient setting; * Taking drugs that could affect cognitive function. * The routine blood tests showing significant abnormal renal, liver function or other somatic disease. * Pregnant or lactating women. **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Jing Huang, MD **Phone:** 15874290980 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Jingmei Xiao, MD **Phone:** 17673129702 **Role:** CONTACT #### Locations **Location 1:** **City:** Changsha **Country:** China **Facility:** Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University **State:** Hunan **Zip:** 410011 #### Overall Officials **Official 1:** **Affiliation:** Department of Psychiatry, The Second Xiangya Hospital of Central South University **Name:** Renrong Wu, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000044882 - Term: Glucose Metabolism Disorders - ID: D000008659 - Term: Metabolic Diseases - ID: D000004700 - Term: Endocrine System Diseases - ID: D000006946 - Term: Hyperinsulinism ### Condition Browse Module - Browse Branches - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: All - Name: All Conditions - Abbrev: BXM - Name: Behaviors and Mental Disorders ### Condition Browse Module - Browse Leaves - ID: M7115 - Name: Diabetes Mellitus - Relevance: HIGH - As Found: Diabetes - ID: M7119 - Name: Diabetes Mellitus, Type 2 - Relevance: HIGH - As Found: Type 2 Diabetes - ID: M29705 - Name: Cognitive Dysfunction - Relevance: LOW - As Found: Unknown - ID: M10370 - Name: Insulin Resistance - Relevance: HIGH - As Found: Insulin Resistance - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown - ID: M25403 - Name: Glucose Metabolism Disorders - Relevance: LOW - As Found: Unknown - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown - ID: M9997 - Name: Hyperinsulinism - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003920 - Term: Diabetes Mellitus - ID: D000003924 - Term: Diabetes Mellitus, Type 2 - ID: D000007333 - Term: Insulin Resistance ### Intervention Browse Module - Ancestors - ID: D000007004 - Term: Hypoglycemic Agents - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: Hypo - Name: Hypoglycemic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M10365 - Name: Insulin - Relevance: HIGH - As Found: Day 1 - ID: M173166 - Name: Insulin, Globin Zinc - Relevance: LOW - As Found: Unknown - ID: M10054 - Name: Hypoglycemic Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000007328 - Term: Insulin ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False

## Protocol Section ### Identification Module **NCT ID:** NCT06428955 **Acronym:** PRECISE **Brief Title:** Evaluation of a Monofocal Intraocular Lens **Official Title:** Prospective Multicenter Evaluation of the Visual Performance of a Non-constant Aberration Correcting Aspheric Monofocal Intraocular Lens (Precise Study)) #### Organization Study ID Info **ID:** GPAS-SAS-023-01 #### Organization **Class:** INDUSTRY **Full Name:** Carl Zeiss Meditec AG ### Status Module #### Completion Date **Date:** 2024-12 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-20 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2024-12 **Type:** ESTIMATED #### Start Date **Date:** 2024-05 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-05-24 **Type:** ACTUAL **Study First Submit Date:** 2024-05-15 **Study First Submit QC Date:** 2024-05-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Carl Zeiss Meditec AG #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** True **Is FDA Regulated Drug:** False **Is US Export:** True **Oversight Has DMC:** False ### Description Module **Brief Summary:** The aim of this study is to investigate the 3-month visual performance of the CT LUCIA 621P IOL, a hydrophobic aspheric monofocal IOL with a non-constant aspheric optic profile in adult patients 50 years of age or older who are undergoing cataract surgery. ### Conditions Module **Conditions:** - Cataract ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 44 **Type:** ESTIMATED **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Monofocal IOL **Intervention Names:** - Device: CT LUCIA 621P **Label:** Bilateral implantation of investigational device **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Bilateral implantation of investigational device **Description:** The device under investigation, CT LUCIA 621P IOL (Carl Zeiss Meditec, Jena, Germany) is a posterior chamber intraocular lens which is indicated for aphakia after surgical extraction of the cataractous natural lens. It is a monofocal aspheric IOL made of hydrophobic material and coated with heparin. The modified C-loop haptic is step-vaulted. **Name:** CT LUCIA 621P **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** The primary efficacy endpoint is the proportion of patients with monocular CDVA of 20/40 or better at three months **Measure:** Monocular best corrected distance visual acuity (CDVA) **Time Frame:** Three (3) Months #### Secondary Outcomes **Measure:** Binocular Corrected Distance Visual Acuity **Time Frame:** Three (3) Months **Measure:** Binocular Uncorrected Corrected Distance Visual Acuity **Time Frame:** Three (3) Months **Measure:** Monocular Uncorrected Visual Acuity **Time Frame:** Three (3) Months **Measure:** Monocular Distance Corrected Intermediate Visual Acuity **Time Frame:** Three (3) Months **Measure:** Monocular Uncorrected Intermediate Visual Acuity **Time Frame:** Three (3) Months **Measure:** Manifest Refraction Spherical Equivalent **Time Frame:** Three (3) Months **Description:** Manifest refraction will be evaluated at 1 and 3 months to determine refractive predictability. The predicted refraction is the goal or target refraction from the IOLMaster IOL calculation and the observed refraction is the 3 Month postoperative Manifest Refraction Spherical Equivalent measurement. **Measure:** Refractive Predictability **Time Frame:** Three (3) Months **Description:** Manifest refraction will be obtained at 1 and 3 months to evaluate whether refractive stability is achieved by 3 months. Refractive stability will be evaluated at the 1 to 3 months interval as a parameter of interest to determine the proportion of eyes that achieve stability of manifest refraction. **Measure:** Refractive Stability **Time Frame:** Three (3) Months **Measure:** Contrast Sensitivity - mesopic and photopic with and without glare **Time Frame:** Three (3) Months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Be at least 50 years of age or older, male or female, of any race or ethnicity. 2. Presenting for uncomplicated bilateral cataract surgery for age-related cataract. 3. Planned bilateral cataract extraction with posterior chamber IOL implantation, via phacoemulsification with or without femtosecond laser assisted cataract surgery (FLACS). 4. Bilateral implantation of a CT LUCIA 621P IOL with a dioptric power between +10.00 D and +30.00 D and a target postoperative refraction of emmetropia (0.00 ±0.50 D). 5. Clear intraocular media other than cataract (i.e. no hyphema, vitreous hemorrhage) 6. No visual acuity limiting pathologies other than cataract. Best corrected postoperative visual acuity potential of 20/25 or better in both eyes as estimated by potential acuity meter or surgeon estimation. 7. Provide written informed consent and a signed HIPPA form. 8. Availability, willingness, ability, and sufficient cognitive awareness to comply with study examination procedures and the schedule for study visits and evaluations. Exclusion Criteria: 1. Corneal Astigmatism of \>1.0 D. 2. Planned monocular cataract extraction. 3. Visual field loss which has an impact on visual acuity. 4. Subjects with intraoperative surgical complications in whom a CT LUCIA 621P IOL cannot be implanted. 5. History of acute or chronic disease, pathology, illness, or ocular trauma that would, in the surgeon's opinion, confound results (e.g., corneal pathology, keratoconus, strabismus, uncontrolled glaucoma) 6. History of Glaucoma, macular degeneration, cystoid macular edema, proliferative diabetic retinopathy, amblyopia, etc. 7. Previous intraocular or corneal surgery, including all forms of refractive surgery that might confound the outcome of the investigation or increase the risk to the subject 8. Previous anterior or posterior chamber surgery other than peripheral retinal barrier laser, SLT/ALT (e.g., vitrectomy, laser iridotomy) 9. Pupil abnormalities (non-reactive, tonic pupils, abnormally shaped pupils or pupils that do not dilate under mesopic/scotopic conditions). 10. Capsular or zonular abnormalities or other conditions that increase the risk of zonular rupture during cataract extraction procedure and/or may affect the postoperative centration or tilt of the lens 11. Use of a systemic or ocular medication that might affect vision and confound the outcome or increase the risk to the subject in the opinion of the investigator such as tamsulosin hydrochloride (Flomax) or other medications with similar side effects (floppy iris syndrome) 12. Cycloplegic pupil diameter \<6.0 mm or the presence of ocular implants that limit pupil diameter (malyugin rings; iris prosthesis). 13. Usage of contact lenses during study participation 14. Pregnant, lactating during the course of the investigation, or has another condition with associated fluctuation of hormones that could lead to refractive changes 15. Presence or history or any other condition or finding that, in the investigator's opinion, makes the subject unsuitable as a candidate for study participation, may increase the operative risk or may confound the outcome of the study. **Healthy Volunteers:** True **Minimum Age:** 50 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Grant Sharpe **Phone:** +447918937014 **Role:** CONTACT ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007905 - Term: Lens Diseases - ID: D000005128 - Term: Eye Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC11 - Name: Eye Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M5638 - Name: Cataract - Relevance: HIGH - As Found: Cataract - ID: M10917 - Name: Lens Diseases - Relevance: LOW - As Found: Unknown - ID: M8271 - Name: Eye Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002386 - Term: Cataract ### Intervention Browse Module - Browse Branches - Abbrev: FiAg - Name: Fibrinolytic Agents - Abbrev: AnCoag - Name: Anticoagulants - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M9579 - Name: Heparin - Relevance: LOW - As Found: Unknown - ID: M46053 - Name: Calcium heparin - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-06-06 **Has Results:** False