Pub Date : 2025-11-19DOI: 10.1016/j.cct.2025.108149
Katherine A. Dondanville , Amber Calloway , Elizabeth C. Stade , Thomas D. Hull , Booil Jo , Szu-chi Huang , Brittany N. Hall-Clark , Stefanie T. LoSavio , Bailee Schuhmann , Sohayla Elhusseini , Nicole Fridling-Cook , Cyrus Pattee , Aarthi Padmanabhan , Shannon Wiltsey Stirman
Posttraumatic stress disorder (PTSD) can be a chronic and debilitating condition with significant individual and societal costs. Despite the availability of effective, trauma-focused treatments like Cognitive Processing Therapy (CPT), access and sustained engagement remain limited due to logistical, financial, and stigma-related barriers. The current study utilized a hybrid effectiveness-implementation randomized control trial (N = 300) to evaluate the clinical effectiveness and feasibility of CPT-Text, an asynchronous, therapist-delivered messaging version of CPT, compared to culturally informed treatment-as-usual (CI-TAU) delivered via secure text on the Talkspace platform. Participants were also randomized to receive either standard engagement reminders (RAU) or a novel engagement incentive (RAU + I), which encourages altruism by offering participants the opportunity to “pay forward” credits for free therapy to another PTSD-affected individual through their continued participation. Primary outcomes include PTSD symptom severity (PCL-5) and engagement (e.g., treatment completion and messaging frequency), with secondary outcomes assessing depression, functioning, satisfaction, substance use. We hypothesize that CPT-Text will outperform CI-TAU in symptom reduction, and that RAU + I will enhance engagement and outcomes. Exploratory analyses will examine individual-level moderators and motivation as a mechanism of change. A novel component of this trial includes development of a large language model–based fidelity assessment tool for CPT-Text, allowing scalable evaluation of treatment delivery. Findings will inform scalable, effective, and accessible PTSD interventions that meet the needs of individuals underserved by traditional mental health care, and provide insight into how human-delivered, technology-mediated therapy can be both clinically robust and broadly accessible. Evaluating Asynchronous Messaging Therapy for PTSD.
{"title":"Evaluating effectiveness and engagement strategies for asynchronous, messaging, trauma-focused therapy for posttraumatic stress disorder: Study design and methodology for a hybrid effectiveness-implementation randomized controlled trial","authors":"Katherine A. Dondanville , Amber Calloway , Elizabeth C. Stade , Thomas D. Hull , Booil Jo , Szu-chi Huang , Brittany N. Hall-Clark , Stefanie T. LoSavio , Bailee Schuhmann , Sohayla Elhusseini , Nicole Fridling-Cook , Cyrus Pattee , Aarthi Padmanabhan , Shannon Wiltsey Stirman","doi":"10.1016/j.cct.2025.108149","DOIUrl":"10.1016/j.cct.2025.108149","url":null,"abstract":"<div><div>Posttraumatic stress disorder (PTSD) can be a chronic and debilitating condition with significant individual and societal costs. Despite the availability of effective, trauma-focused treatments like Cognitive Processing Therapy (CPT), access and sustained engagement remain limited due to logistical, financial, and stigma-related barriers. The current study utilized a hybrid effectiveness-implementation randomized control trial (<em>N</em> = 300) to evaluate the clinical effectiveness and feasibility of <em>CPT-Text</em>, an asynchronous, therapist-delivered messaging version of CPT, compared to culturally informed treatment-as-usual (CI-TAU) delivered via secure text on the Talkspace platform. Participants were also randomized to receive either standard engagement reminders (RAU) or a novel engagement incentive (RAU + I), which encourages altruism by offering participants the opportunity to “pay forward” credits for free therapy to another PTSD-affected individual through their continued participation. Primary outcomes include PTSD symptom severity (PCL-5) and engagement (e.g., treatment completion and messaging frequency), with secondary outcomes assessing depression, functioning, satisfaction, substance use. We hypothesize that CPT-Text will outperform CI-TAU in symptom reduction, and that RAU + I will enhance engagement and outcomes. Exploratory analyses will examine individual-level moderators and motivation as a mechanism of change. A novel component of this trial includes development of a large language model–based fidelity assessment tool for CPT-Text, allowing scalable evaluation of treatment delivery. Findings will inform scalable, effective, and accessible PTSD interventions that meet the needs of individuals underserved by traditional mental health care, and provide insight into how human-delivered, technology-mediated therapy can be both clinically robust and broadly accessible. Evaluating Asynchronous Messaging Therapy for PTSD.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"160 ","pages":"Article 108149"},"PeriodicalIF":1.9,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145570300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-18DOI: 10.1016/j.cct.2025.108152
Jenna Hauben , Jacsen Luthy , Toluwaniose Nafiu , Alexis Brengartner , Mohamed Omar , Donya Nemati , Songzhu Zhao , Guy Brock , Kelly Urse , John Paro , Joshua J. Joseph
Background
Less than 15 % of individuals 65+ meet physical activity guidelines for aerobic and muscle-strengthening activities. Thus, in this study we will examine the feasibility and acceptability of utilizing smartwatches among Exercise is Medicine (EIM), a physician referral exercise program, for participants aged 65+ to improve physical activity.
Methods
We will conduct a single-arm trial. Participants will complete an 11-week exercise program combined with a smartwatch, monthly webinars, and two follow-up sessions at 6 and 12 months. Surveys will measure acceptability of the exercise program and the wearable smartwatch. The number of active participants, participant attendance and program completion rates will assess feasibility of the program.
Setting
Ambulatory care clinics affiliated with a medical center and community centers in Central Ohio.
Design
Single-arm pilot study.
Interventions
FASTER will consist of 3 one-on-one and 16 group sessions over 11 weeks in addition to wellness webinars and two follow-up one-on-one sessions 6 and 12 months after program completion. The one-on-one and group sessions will be led by an American College of Sports Medicine (ACSM) certified exercise physiologist with EIM credentials. All participants will receive a Fitbit smartwatch to use throughout the program.
Outcomes
The primary outcome is the feasibility and acceptability of FASTER. Secondary outcomes are change in physical activity, biometric measures, mental health, and quality of life.
Discussion
Incorporating wearable smartwatch technology into a physician referral exercise program may be a novel way to improve physical activity and health in older adults.
{"title":"Rationale for the Feasibility and Acceptability of Smartwatch Technology in an Exercise Regimen (FASTER) study in older individuals","authors":"Jenna Hauben , Jacsen Luthy , Toluwaniose Nafiu , Alexis Brengartner , Mohamed Omar , Donya Nemati , Songzhu Zhao , Guy Brock , Kelly Urse , John Paro , Joshua J. Joseph","doi":"10.1016/j.cct.2025.108152","DOIUrl":"10.1016/j.cct.2025.108152","url":null,"abstract":"<div><h3>Background</h3><div>Less than 15 % of individuals 65+ meet physical activity guidelines for aerobic and muscle-strengthening activities. Thus, in this study we will examine the feasibility and acceptability of utilizing smartwatches among Exercise is Medicine (EIM), a physician referral exercise program, for participants aged 65+ to improve physical activity.</div></div><div><h3>Methods</h3><div>We will conduct a single-arm trial. Participants will complete an 11-week exercise program combined with a smartwatch, monthly webinars, and two follow-up sessions at 6 and 12 months. Surveys will measure acceptability of the exercise program and the wearable smartwatch. The number of active participants, participant attendance and program completion rates will assess feasibility of the program.</div></div><div><h3>Setting</h3><div>Ambulatory care clinics affiliated with a medical center and community centers in Central Ohio.</div></div><div><h3>Design</h3><div>Single-arm pilot study.</div></div><div><h3>Interventions</h3><div>FASTER will consist of 3 one-on-one and 16 group sessions over 11 weeks in addition to wellness webinars and two follow-up one-on-one sessions 6 and 12 months after program completion. The one-on-one and group sessions will be led by an American College of Sports Medicine (ACSM) certified exercise physiologist with EIM credentials. All participants will receive a Fitbit smartwatch to use throughout the program.</div></div><div><h3>Outcomes</h3><div>The primary outcome is the feasibility and acceptability of FASTER. Secondary outcomes are change in physical activity, biometric measures, mental health, and quality of life.</div></div><div><h3>Discussion</h3><div>Incorporating wearable smartwatch technology into a physician referral exercise program may be a novel way to improve physical activity and health in older adults.</div><div>Clinical Trial Registration Number: <span><span>NCT06287255</span><svg><path></path></svg></span></div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"160 ","pages":"Article 108152"},"PeriodicalIF":1.9,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145563109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-18DOI: 10.1016/j.cct.2025.108145
Gelareh Sadigh , Fenghai Duan , Ilana F. Gareen , Judy Hancock , JoRean D. Sicks , Maryanne Thangarajah , Jane L. Meisel , Mylin A. Torres , Scott D. Ramsey , Antonio C. Wolff , Lynne I. Wagner , Ruth C. Carlos , Ilana Graetz
Background
Cyclin-dependent kinase 4/6 inhibitors (CDKIs) improves survival when added to endocrine therapy in hormone receptor-positive (HR+), human epidermal growth factor receptor 2–negative (HER2-) breast cancer. However, their complex schedule, side effects, and cost contribute to non-adherence.
Methods
The EAQ221CD is a two-arm randomized controlled trial that evaluates the effectiveness of the CONnected CUstomized Treatment Platform (CONCURxP), a mobile health intervention, versus enhanced usual care (EUC) on CDKI adherence among 390 patients with breast cancer and a new CDKI prescription. Participants use a smart pouch (Wisebag) to monitor real-time adherence. CONCURxP arm patients: (1) receive text reminders for missed or extra doses; (2) receive text message surveys inquiring reasons for missed or extra doses; and (3) have access to their adherence history on a study web portal. Missed or double doses trigger alerts to the oncology team. Patients citing cost as a barrier are referred to a national non-profit financial navigation program. EUC arm patients receive educational materials on side effect management. Patients complete surveys at baseline, 3, 6, and 12 months after randomization. Our objectives are to: (1) compare 12-month CDKI adherence measured using Wisebag (primary outcome) between the two arms; (2) compare patient-reported outcomes at 12-months between the two arms, including symptom burden, quality of life, patient-provider communication, self-efficacy for managing symptoms, and financial worry; and (3) use mixed methods to describe patients' experience with the CONCURxP intervention. Our multilevel intervention will provide actionable results to improve adherence, health outcomes, and patients' experience.
{"title":"Improving CDK4/6 inhibitors adherence in breast cancer using the CONnected CUstomized Treatment Platform (CONCURxP) mobile health intervention: Study protocol for ECOG-ACRIN EAQ221CD","authors":"Gelareh Sadigh , Fenghai Duan , Ilana F. Gareen , Judy Hancock , JoRean D. Sicks , Maryanne Thangarajah , Jane L. Meisel , Mylin A. Torres , Scott D. Ramsey , Antonio C. Wolff , Lynne I. Wagner , Ruth C. Carlos , Ilana Graetz","doi":"10.1016/j.cct.2025.108145","DOIUrl":"10.1016/j.cct.2025.108145","url":null,"abstract":"<div><h3>Background</h3><div>Cyclin-dependent kinase 4/6 inhibitors (CDKIs) improves survival when added to endocrine therapy in hormone receptor-positive (HR+), human epidermal growth factor receptor 2–negative (HER2-) breast cancer. However, their complex schedule, side effects, and cost contribute to non-adherence.</div></div><div><h3>Methods</h3><div>The EAQ221CD is a two-arm randomized controlled trial that evaluates the effectiveness of the CONnected CUstomized Treatment Platform (CONCURxP), a mobile health intervention, versus enhanced usual care (EUC) on CDKI adherence among 390 patients with breast cancer and a new CDKI prescription. Participants use a smart pouch (Wisebag) to monitor real-time adherence. CONCURxP arm patients: (1) receive text reminders for missed or extra doses; (2) receive text message surveys inquiring reasons for missed or extra doses; and (3) have access to their adherence history on a study web portal. Missed or double doses trigger alerts to the oncology team. Patients citing cost as a barrier are referred to a national non-profit financial navigation program. EUC arm patients receive educational materials on side effect management. Patients complete surveys at baseline, 3, 6, and 12 months after randomization. Our objectives are to: (1) compare 12-month CDKI adherence measured using Wisebag (primary outcome) between the two arms; (2) compare patient-reported outcomes at 12-months between the two arms, including symptom burden, quality of life, patient-provider communication, self-efficacy for managing symptoms, and financial worry; and (3) use mixed methods to describe patients' experience with the CONCURxP intervention. Our multilevel intervention will provide actionable results to improve adherence, health outcomes, and patients' experience.</div><div><strong>Trial registration:</strong> NCT06112613.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"160 ","pages":"Article 108145"},"PeriodicalIF":1.9,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145563155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-17DOI: 10.1016/j.cct.2025.108147
Folasade P. May , Jenna A. McEwan , Jessica J. Tuan , Catherine M. Crespi , Cleo K. Maehara , Jamie O. Yang , Alexandria Uy , Samir Gupta , Yuna Kang , Anthony Myint , Bita V. Naini , Joann G. Elmore , Srikanth Kadiyala , Michael K. Ong , Alex A.T. Bui , Alison B. Hamilton , L. Cindy Chang , Alex Gelvezon , William Hsu , Roshan Bastani
Introduction
Colorectal cancer (CRC) is largely preventable through the removal of precancerous polyps from the colon and rectum. Polyp surveillance guidelines recommend that individuals with polyps categorized as high-risk neoplasia (HRN) undergo surveillance colonoscopy 3 years after HRN diagnosis. However, over half of patients fail to receive their surveillance colonoscopy within this recommended timeframe, highlighting the need for effective interventions to improve 3-year colonoscopy surveillance rates.
Methods
A hybrid type 1 effectiveness-implementation, 2-group cluster-randomized trial is being conducted at 30 primary health care clinics in a large, urban academic health center in Southern California. The study includes two arms: (1) a multilevel intervention arm in which a natural language processing (NLP) algorithm processes electronic health record (EHR) data to facilitate the identification of patients with HRN and providers and patients receive electronic notification when surveillance colonoscopy is due; and (2) a usual care arm, where no intervention is applied.
Results
The primary outcome will be completion of surveillance colonoscopy within 3.5 years of the HRN diagnosis. The secondary outcome will be time from the HRN diagnosis to completion of surveillance colonoscopy.
Conclusions
This study evaluates the effectiveness of a multilevel health system intervention designed to improve adherence to surveillance colonoscopy guidelines for patients with a history of high-risk colorectal polyps. The findings are expected to offer valuable insights into strategies for leveraging EHR-informed algorithms to increase surveillance rates and improve CRC outcomes.
{"title":"Increasing timely colonoscopy surveillance for patients with high-risk colorectal polyps: Protocol for a cluster randomized trial","authors":"Folasade P. May , Jenna A. McEwan , Jessica J. Tuan , Catherine M. Crespi , Cleo K. Maehara , Jamie O. Yang , Alexandria Uy , Samir Gupta , Yuna Kang , Anthony Myint , Bita V. Naini , Joann G. Elmore , Srikanth Kadiyala , Michael K. Ong , Alex A.T. Bui , Alison B. Hamilton , L. Cindy Chang , Alex Gelvezon , William Hsu , Roshan Bastani","doi":"10.1016/j.cct.2025.108147","DOIUrl":"10.1016/j.cct.2025.108147","url":null,"abstract":"<div><h3>Introduction</h3><div>Colorectal cancer (CRC) is largely preventable through the removal of precancerous polyps from the colon and rectum. Polyp surveillance guidelines recommend that individuals with polyps categorized as high-risk neoplasia (HRN) undergo surveillance colonoscopy 3 years after HRN diagnosis. However, over half of patients fail to receive their surveillance colonoscopy within this recommended timeframe, highlighting the need for effective interventions to improve 3-year colonoscopy surveillance rates.</div></div><div><h3>Methods</h3><div>A hybrid type 1 effectiveness-implementation, 2-group cluster-randomized trial is being conducted at 30 primary health care clinics in a large, urban academic health center in Southern California. The study includes two arms: (1) a multilevel intervention arm in which a natural language processing (NLP) algorithm processes electronic health record (EHR) data to facilitate the identification of patients with HRN and providers and patients receive electronic notification when surveillance colonoscopy is due; and (2) a usual care arm, where no intervention is applied.</div></div><div><h3>Results</h3><div>The primary outcome will be completion of surveillance colonoscopy within 3.5 years of the HRN diagnosis. The secondary outcome will be time from the HRN diagnosis to completion of surveillance colonoscopy.</div></div><div><h3>Conclusions</h3><div>This study evaluates the effectiveness of a multilevel health system intervention designed to improve adherence to surveillance colonoscopy guidelines for patients with a history of high-risk colorectal polyps. The findings are expected to offer valuable insights into strategies for leveraging EHR-informed algorithms to increase surveillance rates and improve CRC outcomes.</div><div>Trial Registration: <span><span>NCT06376565</span><svg><path></path></svg></span></div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"160 ","pages":"Article 108147"},"PeriodicalIF":1.9,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145556444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-17DOI: 10.1016/j.cct.2025.108151
Laurie Keefer , Ryan Ungaro , Ayanna Lewis , Josie Lee , Candela de Amorrortu , Taryn Lores , Tina Siganporia , Saurabh Mehandru , Francesca Petralia , Jean-Frederic Colombel
Background
Remission rates in Crohn's disease (CD) with standard therapies have plateaued in recent decades. There is a need to investigate more innovative strategies to raise the “therapeutic ceiling”. Combining orthogonal treatments that target differing pathways of disease pathogenesis may maximize synergistic therapeutic efficacy. In particular, the addition of interventions that target the gut-brain axis warrant investigation. Our overarching goal is to demonstrate the value of a new “combination therapy” that addresses psychological and physical health simultaneously, targeting the gut-brain axis, to improve CD outcomes. We will test the efficacy of combining brain-gut behavior therapy with biologic treatment in a randomized, controlled clinical trial, following behavioral clinical trial guidelines for gastroenterology.
Methods
We will recruit 170 adults with CD aged between 18 and 80 years starting an anti-tumor necrosis factor or anti-interleukin-23 medication. Participants will be randomized in a 1:1 ratio to receive a program of either brain-gut behavioral therapy (intervention group) or emotional support (time and attention control group). Both programs consist of seven sessions within a 12-week period. Patient-reported outcomes including well-being and disease activity will be measured at weeks 0, 12, 24, 36, and 52, with the primary outcomes reflected at week 24. Outcomes will be evaluated for group X time interactions.
Conclusions
This trial will be the first of its kind to rigorously evaluate the efficacy of a treatment approach that combines brain-gut behavioral therapy and biologics for people with CD.
{"title":"Combination Therapy of Resilience Intervention with Biologics in Crohn's Disease (CATHARSIS): Study protocol for a randomized controlled trial","authors":"Laurie Keefer , Ryan Ungaro , Ayanna Lewis , Josie Lee , Candela de Amorrortu , Taryn Lores , Tina Siganporia , Saurabh Mehandru , Francesca Petralia , Jean-Frederic Colombel","doi":"10.1016/j.cct.2025.108151","DOIUrl":"10.1016/j.cct.2025.108151","url":null,"abstract":"<div><h3>Background</h3><div>Remission rates in Crohn's disease (CD) with standard therapies have plateaued in recent decades. There is a need to investigate more innovative strategies to raise the “therapeutic ceiling”. Combining orthogonal treatments that target differing pathways of disease pathogenesis may maximize synergistic therapeutic efficacy. In particular, the addition of interventions that target the gut-brain axis warrant investigation. Our overarching goal is to demonstrate the value of a new “combination therapy” that addresses psychological and physical health simultaneously, targeting the gut-brain axis, to improve CD outcomes. We will test the efficacy of combining brain-gut behavior therapy with biologic treatment in a randomized, controlled clinical trial, following behavioral clinical trial guidelines for gastroenterology.</div></div><div><h3>Methods</h3><div>We will recruit 170 adults with CD aged between 18 and 80 years starting an anti-tumor necrosis factor or anti-interleukin-23 medication. Participants will be randomized in a 1:1 ratio to receive a program of either brain-gut behavioral therapy (intervention group) or emotional support (time and attention control group). Both programs consist of seven sessions within a 12-week period. Patient-reported outcomes including well-being and disease activity will be measured at weeks 0, 12, 24, 36, and 52, with the primary outcomes reflected at week 24. Outcomes will be evaluated for group X time interactions.</div></div><div><h3>Conclusions</h3><div>This trial will be the first of its kind to rigorously evaluate the efficacy of a treatment approach that combines brain-gut behavioral therapy and biologics for people with CD.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"160 ","pages":"Article 108151"},"PeriodicalIF":1.9,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145556472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-17DOI: 10.1016/j.cct.2025.108150
Yingying Luo , Hongwei Jiang , Bimin Shi , Hanqing Cai , Haifang Wang , Shu Li , Wei Qiu , Yunfeng Li , Runze Zhou , Huan Deng , Qun Guo , Li Li , Lijuan Pei , Han Han Zhang , Lei Qian , Linong Ji
Background
Effective weight management and glycemic control are both important in people with type 2 diabetes (T2D) and obesity. Despite the proven benefits of GLP-1 receptor agonists, there is a persistent need for more effective weight management strategies in the treatment of T2D and obesity. Glucagon receptor-based co-agonists, such as mazdutide, represent a promising therapeutic class with the potential for enhanced weight loss compared to current standards of care. However, robust clinical evidence for these agents in populations with T2D and obesity is still lacking. The DREAMS-3 trial is designed to address this gap by directly comparing the efficacy and safety of mazdutide against semaglutide, a widely used GLP-1 receptor agonist, in Chinese adults with T2D and obesity. The results will provide crucial evidence to inform clinical decision-making for this large patient population.
Methods
DREAMS-3 is a randomized, open-label phase 3 trial. Obese Participants (BMI ≥ 28 kg/m2) diagnosed with T2D (≤ 10 years) who had inadequate glycemic control after diet and exercise alone with/without metformin were randomized in a 1:1 ratio to receive mazdutide 6 mg or semaglutide 1 mg once weekly in the 32-week active-controlled treatment period, followed with a 24-week extension period. The primary endpoint is the proportion of participants achieving glycated hemoglobin <7.0 % and weight reduction of ≥10 % at week 32.
Results
A total of 349 participants were enrolled and randomized, the overall mean age was 42.4 years, 44.7 % of participants were male. The mean baseline duration of T2D was 1.8 years, and 39.5 % of participants were on metformin. The mean glycated hemoglobin was 8.0 %, body weight was 90.5 kg, BMI was 33.0 kg/m2. Most participants had at least one comorbidity. The prevalence of some comorbidities (such as metabolic associated fatty liver disease, gout/hyperuricemia) showed strong association of BMI.
Conclusion
DERAMS-3 is the first head-to-head trial to compare the efficacy and safety of mazdutide versus semaglutide in Chinese adults with T2D and obesity, with an expected completion date in early 2026.
{"title":"Mazdutide versus Semaglutide for the treatment of type 2 diabetes and obesity: Rationale, design and baseline data of DREAMS-3 phase 3 trial","authors":"Yingying Luo , Hongwei Jiang , Bimin Shi , Hanqing Cai , Haifang Wang , Shu Li , Wei Qiu , Yunfeng Li , Runze Zhou , Huan Deng , Qun Guo , Li Li , Lijuan Pei , Han Han Zhang , Lei Qian , Linong Ji","doi":"10.1016/j.cct.2025.108150","DOIUrl":"10.1016/j.cct.2025.108150","url":null,"abstract":"<div><h3>Background</h3><div>Effective weight management and glycemic control are both important in people with type 2 diabetes (T2D) and obesity. Despite the proven benefits of GLP-1 receptor agonists, there is a persistent need for more effective weight management strategies in the treatment of T2D and obesity. Glucagon receptor-based co-agonists, such as mazdutide, represent a promising therapeutic class with the potential for enhanced weight loss compared to current standards of care. However, robust clinical evidence for these agents in populations with T2D and obesity is still lacking. The DREAMS-3 trial is designed to address this gap by directly comparing the efficacy and safety of mazdutide against semaglutide, a widely used GLP-1 receptor agonist, in Chinese adults with T2D and obesity. The results will provide crucial evidence to inform clinical decision-making for this large patient population.</div></div><div><h3>Methods</h3><div>DREAMS-3 is a randomized, open-label phase 3 trial. Obese Participants (BMI ≥ 28 kg/m<sup>2</sup>) diagnosed with T2D (≤ 10 years) who had inadequate glycemic control after diet and exercise alone with/without metformin were randomized in a 1:1 ratio to receive mazdutide 6 mg or semaglutide 1 mg once weekly in the 32-week active-controlled treatment period, followed with a 24-week extension period. The primary endpoint is the proportion of participants achieving glycated hemoglobin <7.0 % and weight reduction of ≥10 % at week 32.</div></div><div><h3>Results</h3><div>A total of 349 participants were enrolled and randomized, the overall mean age was 42.4 years, 44.7 % of participants were male. The mean baseline duration of T2D was 1.8 years, and 39.5 % of participants were on metformin. The mean glycated hemoglobin was 8.0 %, body weight was 90.5 kg, BMI was 33.0 kg/m<sup>2</sup>. Most participants had at least one comorbidity. The prevalence of some comorbidities (such as metabolic associated fatty liver disease, gout/hyperuricemia) showed strong association of BMI.</div></div><div><h3>Conclusion</h3><div>DERAMS-3 is the first head-to-head trial to compare the efficacy and safety of mazdutide versus semaglutide in Chinese adults with T2D and obesity, with an expected completion date in early 2026.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"160 ","pages":"Article 108150"},"PeriodicalIF":1.9,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145556413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-11DOI: 10.1016/j.cct.2025.108140
Taylor Kohlmann , Angel Chen , Polly Armsby , C. Ashley Finlen Copeland , Tracy Gentry , Marla Jordan , Maurine Morris , Ana Trampe , Jyoti Angal , Lauren Sims Taylor , Annemarie Stroustrup , Carlos A. Camargo Jr. , N. David Yanez , P. Brian Smith , for the ECHO Cohort Consortium
Background
Institutional review board (IRB) approval is a key step in site activation and study initiation. Single IRBs aim to improve the timeliness of IRB review through centralization and standardization, whereas local IRBs conduct reviews only for specific sites. In Cycle 1 of the Environmental influences on Child Health Outcomes (ECHO) Cohort Consortium, 110 sites chose either single or local IRB review, providing the opportunity to compare the efficiency of single versus local IRBs within one multicenter observational study.
Objectives
Data were collected from the ECHO Coordinating Center at the Duke Clinical Research Institute. Primary outcomes included: 1) time from IRB submission to approval and 2) time from regulatory pack receipt to first participant enrollment. Secondary outcomes included: 1) time from regulatory pack receipt to IRB submission, 2) time from IRB approval to site activation, and 3) time from site activation to first participant enrollment. We compared these outcomes between sites using local versus single IRBs.
Results
No significant differences were identified between the local and single IRB groups for the primary and secondary outcomes. The time from IRB submission to approval was similar for local and single IRBs (median [IQR]: 20 days [10−33]; 19 days [11–27]; p = 0.71, respectively). The time from regulatory pack receipt to first participant enrollment was similar for local and single IRBs (median [IQR]: 243 days [16–309]; 191 days [137–233]; p = 0.50, respectively).
Conclusion
Multiple factors influence review timelines. Single IRBs do not guarantee faster review; additional work is needed to evaluate their impact on study timelines.
{"title":"A comparison of institutional review board models and study efficiency in the Environmental influences on Child Health Outcomes Cohort Consortium","authors":"Taylor Kohlmann , Angel Chen , Polly Armsby , C. Ashley Finlen Copeland , Tracy Gentry , Marla Jordan , Maurine Morris , Ana Trampe , Jyoti Angal , Lauren Sims Taylor , Annemarie Stroustrup , Carlos A. Camargo Jr. , N. David Yanez , P. Brian Smith , for the ECHO Cohort Consortium","doi":"10.1016/j.cct.2025.108140","DOIUrl":"10.1016/j.cct.2025.108140","url":null,"abstract":"<div><h3>Background</h3><div>Institutional review board (IRB) approval is a key step in site activation and study initiation. Single IRBs aim to improve the timeliness of IRB review through centralization and standardization, whereas local IRBs conduct reviews only for specific sites. In Cycle 1 of the Environmental influences on Child Health Outcomes (ECHO) Cohort Consortium, 110 sites chose either single or local IRB review, providing the opportunity to compare the efficiency of single versus local IRBs within one multicenter observational study.</div></div><div><h3>Objectives</h3><div>Data were collected from the ECHO Coordinating Center at the Duke Clinical Research Institute. Primary outcomes included: 1) time from IRB submission to approval and 2) time from regulatory pack receipt to first participant enrollment. Secondary outcomes included: 1) time from regulatory pack receipt to IRB submission, 2) time from IRB approval to site activation, and 3) time from site activation to first participant enrollment. We compared these outcomes between sites using local versus single IRBs.</div></div><div><h3>Results</h3><div>No significant differences were identified between the local and single IRB groups for the primary and secondary outcomes. The time from IRB submission to approval was similar for local and single IRBs (median [IQR]: 20 days [10−33]; 19 days [11–27]; <em>p</em> = 0.71, respectively). The time from regulatory pack receipt to first participant enrollment was similar for local and single IRBs (median [IQR]: 243 days [16–309]; 191 days [137–233]; <em>p</em> = 0.50, respectively).</div></div><div><h3>Conclusion</h3><div>Multiple factors influence review timelines. Single IRBs do not guarantee faster review; additional work is needed to evaluate their impact on study timelines.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"160 ","pages":"Article 108140"},"PeriodicalIF":1.9,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145511913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-11DOI: 10.1016/j.cct.2025.108143
Hannah E. Cabre , Courtney M. Peterson , Gareth R. Dutton , Kimberly L. Drews , Stephanie T. Broyles , Robert Dubin , Laura Q. Rogers , Catherine Champagne , Dennis T. Villareal , Daniel S. Hsia , Leanne M. Redman , Corby K. Martin
Background
Understanding the impact of nutrition on human aging requires long-term trials in young, healthy, unmedicated adults. As part of the Dietary Approaches for Longevity and Health (DiAL Health) pilot project, we evaluated strategies for recruiting this population for aging-related dietary intervention studies.
Methods
We analyzed recruitment costs to enroll 70 participants (ages 25–49, BMI 22.0–29.9 kg/m2) across two DiAL Health sites and used NHANES data (2017–March 2020) to estimate the proportion of U.S. adults meeting partial trial eligibility. Additionally, a formative study surveyed 492 U.S. adults (≥18 years) to assess interest in aging-focused dietary trials.
Results
Of 2049 applicants screened, 70 were enrolled (3.4 %), with recruitment costs of $1572 per participant at site 1 and $625 at site 2. NHANES data revealed only 3.6 % (555/15,560) of adults met partial eligibility criteria, while 2.2 % (11/492) of formative survey respondents met full eligibility. DiAL Health eligible participants were willing to participate in dietary interventions like time-restricted eating or caloric restriction, but willingness declined for longer or more burdensome trials.
Conclusions
Recruiting young, healthy, unmedicated individuals for aging-focused dietary intervention trials is challenging due to low rates of eligibility and enrollment (∼3–4 % of initial applicants enrolled). Longer trials with stricter eligibility are likely to face greater recruitment barriers, highlighting the need for targeted strategies to engage, recruit, and retain this population effectively.
{"title":"Strategies and challenges for the recruitment of young healthy participants in the dietary approaches to longevity and health (DiAL health) pilot trial","authors":"Hannah E. Cabre , Courtney M. Peterson , Gareth R. Dutton , Kimberly L. Drews , Stephanie T. Broyles , Robert Dubin , Laura Q. Rogers , Catherine Champagne , Dennis T. Villareal , Daniel S. Hsia , Leanne M. Redman , Corby K. Martin","doi":"10.1016/j.cct.2025.108143","DOIUrl":"10.1016/j.cct.2025.108143","url":null,"abstract":"<div><h3>Background</h3><div>Understanding the impact of nutrition on human aging requires long-term trials in young, healthy, unmedicated adults. As part of the Dietary Approaches for Longevity and Health (DiAL Health) pilot project, we evaluated strategies for recruiting this population for aging-related dietary intervention studies.</div></div><div><h3>Methods</h3><div>We analyzed recruitment costs to enroll 70 participants (ages 25–49, BMI 22.0–29.9 kg/m<sup>2</sup>) across two DiAL Health sites and used NHANES data (2017–March 2020) to estimate the proportion of U.S. adults meeting partial trial eligibility. Additionally, a formative study surveyed 492 U.S. adults (≥18 years) to assess interest in aging-focused dietary trials.</div></div><div><h3>Results</h3><div>Of 2049 applicants screened, 70 were enrolled (3.4 %), with recruitment costs of $1572 per participant at site 1 and $625 at site 2. NHANES data revealed only 3.6 % (555/15,560) of adults met partial eligibility criteria, while 2.2 % (11/492) of formative survey respondents met full eligibility. DiAL Health eligible participants were willing to participate in dietary interventions like time-restricted eating or caloric restriction, but willingness declined for longer or more burdensome trials.</div></div><div><h3>Conclusions</h3><div>Recruiting young, healthy, unmedicated individuals for aging-focused dietary intervention trials is challenging due to low rates of eligibility and enrollment (∼3–4 % of initial applicants enrolled). Longer trials with stricter eligibility are likely to face greater recruitment barriers, highlighting the need for targeted strategies to engage, recruit, and retain this population effectively.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"160 ","pages":"Article 108143"},"PeriodicalIF":1.9,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145511947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-10DOI: 10.1016/j.cct.2025.108142
Anthony A. Sochet , Ernest K. Amankwah , Vahid Andalib , Julie Jaffray , Christoph Male , E. Vincent Faustino , Neil A. Goldenberg , on behalf of the Pedi-ATLAS Group and the Antithrombotic Trials Working Party of the Pediatric Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis
The efficiency and generalizability of the traditional randomized clinical trial (RCT) design are reduced by the exclusion of otherwise eligible participants who decline randomization or undergo early withdrawal due to missed protocol-specified windows for randomization and/or first dose of the investigational drug. These limitations are particularly challenging for RCTs targeting rare diseases. In this report, we describe a novel adaptation to the previously-described “parallel-cohort RCT design”, in which these up-front losses in an RCT are recaptured into a parallel, non-randomized, contemporaneous control cohort that augments the randomized controls. We also outline various statistical approaches employed to assure congruence of this non-randomized control group to the control arm of the randomized population, prior to analysis. Lastly, we describe the application of the “contemporaneous control recapture” parallel-cohort RCT design in the CRITICAL-Kids-TP trial (www.clinicaltrials.gov; NCT06628778), a proposed phase 3 trial of pharmacological thromboprophylaxis versus usual care (no pharmacological thromboprophylaxis) in critically ill adolescents.
{"title":"Enhanced trial efficiency of the novel “contemporaneous control recapture” parallel-cohort RCT design: Methods and application in the CRITICAL-kids-TP trial","authors":"Anthony A. Sochet , Ernest K. Amankwah , Vahid Andalib , Julie Jaffray , Christoph Male , E. Vincent Faustino , Neil A. Goldenberg , on behalf of the Pedi-ATLAS Group and the Antithrombotic Trials Working Party of the Pediatric Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis","doi":"10.1016/j.cct.2025.108142","DOIUrl":"10.1016/j.cct.2025.108142","url":null,"abstract":"<div><div>The efficiency and generalizability of the traditional randomized clinical trial (RCT) design are reduced by the exclusion of otherwise eligible participants who decline randomization or undergo early withdrawal due to missed protocol-specified windows for randomization and/or first dose of the investigational drug. These limitations are particularly challenging for RCTs targeting rare diseases. In this report, we describe a novel adaptation to the previously-described “parallel-cohort RCT design”, in which these up-front losses in an RCT are recaptured into a parallel, non-randomized, contemporaneous control cohort that augments the randomized controls. We also outline various statistical approaches employed to assure congruence of this non-randomized control group to the control arm of the randomized population, prior to analysis. Lastly, we describe the application of the “contemporaneous control recapture” parallel-cohort RCT design in the CRITICAL-Kids-TP trial (<span><span>www.clinicaltrials.gov</span><svg><path></path></svg></span>; <span><span>NCT06628778</span><svg><path></path></svg></span>), a proposed phase 3 trial of pharmacological thromboprophylaxis versus usual care (no pharmacological thromboprophylaxis) in critically ill adolescents.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"160 ","pages":"Article 108142"},"PeriodicalIF":1.9,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145502483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-09DOI: 10.1016/j.cct.2025.108144
Ana Gabriela Pires dos Santos , Manal Abunimeh , Beatriz Mothe , Jean-Pierre Routy , Jacob P. Lalezari , Gary I. Sinclair , Simiso M. Sokhela , Ricardo Sobhie Diaz , Siegfried Schwarze , Jeff Berry , Sharon R. Lewin , Karine Dubé , Preethi Krishnan , Andrew Topp , Sarah Gill , Daniel Cohen
Background
Immune-mediated interventions have the potential to induce long-term antiretroviral treatment (ART)-free viral suppression in people with HIV. However, in the absence of biomarkers of viral control, studies looking at immune interventions require a planned long-term analytical treatment interruption (ATI) that may bring risks to participants and challenges for data interpretation. Herein, we describe an ongoing, global, proof-of-concept, randomized, placebo-controlled, phase 2 clinical trial with a planned ATI and illustrate how those risks have been mitigated to safely evaluate the long-term durability of ART-free viral control.
Methods
The trial evaluates an immunologic combination of low-dose budigalimab and trosunilimab administered during ATI. Adults aged 18–70 with confirmed HIV-1 on stable ART with viremia below the limit of detection and CD4+ counts >500 cells/mL willing to undergo ATI are randomized to receive budigalimab, trosunilimab, both (at 2 different trosunilimab doses), or neither. The primary efficacy endpoint is the proportion of participants achieving viral control (HIV-1 RNA <1000 copies/mL) without restarting ART at week 24. The planned ATI duration (≤112 weeks) evaluates the durability of off-ART viral control, long-term safety, and biomarkers. Key ATI elements align with published consensus recommendations [1] while incorporating feedback from members of the global HIV community.
Conclusions
By sharing this study design, we hope to inform on the lessons learned from operationalizing a global study evaluating durable ART-free viral control, including the critical role of engaging members of the HIV community during clinical trial design to ensure the success of an ATI-inclusive study.
{"title":"Analytical treatment interruption as a tool in the evaluation of immune-mediated interventions for long-term antiretroviral-free control of HIV-1 among people with HIV","authors":"Ana Gabriela Pires dos Santos , Manal Abunimeh , Beatriz Mothe , Jean-Pierre Routy , Jacob P. Lalezari , Gary I. Sinclair , Simiso M. Sokhela , Ricardo Sobhie Diaz , Siegfried Schwarze , Jeff Berry , Sharon R. Lewin , Karine Dubé , Preethi Krishnan , Andrew Topp , Sarah Gill , Daniel Cohen","doi":"10.1016/j.cct.2025.108144","DOIUrl":"10.1016/j.cct.2025.108144","url":null,"abstract":"<div><h3>Background</h3><div>Immune-mediated interventions have the potential to induce long-term antiretroviral treatment (ART)-free viral suppression in people with HIV. However, in the absence of biomarkers of viral control, studies looking at immune interventions require a planned long-term analytical treatment interruption (ATI) that may bring risks to participants and challenges for data interpretation. Herein, we describe an ongoing, global, proof-of-concept, randomized, placebo-controlled, phase 2 clinical trial with a planned ATI and illustrate how those risks have been mitigated to safely evaluate the long-term durability of ART-free viral control.</div></div><div><h3>Methods</h3><div>The trial evaluates an immunologic combination of low-dose budigalimab and trosunilimab administered during ATI. Adults aged 18–70 with confirmed HIV-1 on stable ART with viremia below the limit of detection and CD4+ counts >500 cells/mL willing to undergo ATI are randomized to receive budigalimab, trosunilimab, both (at 2 different trosunilimab doses), or neither. The primary efficacy endpoint is the proportion of participants achieving viral control (HIV-1 RNA <1000 copies/mL) without restarting ART at week 24. The planned ATI duration (≤112 weeks) evaluates the durability of off-ART viral control, long-term safety, and biomarkers. Key ATI elements align with published consensus recommendations [<span><span>1</span></span>] while incorporating feedback from members of the global HIV community.</div></div><div><h3>Conclusions</h3><div>By sharing this study design, we hope to inform on the lessons learned from operationalizing a global study evaluating durable ART-free viral control, including the critical role of engaging members of the HIV community during clinical trial design to ensure the success of an ATI-inclusive study.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"160 ","pages":"Article 108144"},"PeriodicalIF":1.9,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145494890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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