Pub Date : 2026-01-13DOI: 10.1016/j.cct.2026.108220
Peijin Wang , Hwanhee Hong , Kyungeun Jeon , Laine Elliott Thomas
As the availability of real-world data has expanded in recent years, studies leveraging external controls (ECs) have emerged as potential alternatives to conventional randomized controlled trials (RCTs). While RCTs remain the gold standard for estimating treatment effects, in some contexts, such as rare diseases, it is infeasible or unethical to enroll and randomize a sufficient number of patients. In such cases, it may be justified to conduct a hybrid or single-arm trial that incorporates EC data. This integration first depends on the harmonization of inclusion criteria, covariates, and outcomes, and then requires appropriate statistical methods that account for differences between the trial and EC patients. The propensity score (PS) has emerged as a valuable tool to summarize such differences in patient characteristics. The PS may contribute to a range of estimation methods, including balancing weights, augmented estimators, and Bayesian methods for dynamic borrowing. However, in the context of trials with ECs, the interpretation of the PS and associated causal estimands is often unclear. Motivated by the LIMIT-JIA trial of juvenile idiopathic arthritis, we elucidate potential estimands and evaluate the performance of PS-weighted estimators. We show that some estimands are easier to estimate than others, with potentially greater feasibility for small studies like LIMIT-JIA.
{"title":"Trials augmented by external control data using balancing weights: A comparison of estimands and estimators","authors":"Peijin Wang , Hwanhee Hong , Kyungeun Jeon , Laine Elliott Thomas","doi":"10.1016/j.cct.2026.108220","DOIUrl":"10.1016/j.cct.2026.108220","url":null,"abstract":"<div><div>As the availability of real-world data has expanded in recent years, studies leveraging external controls (ECs) have emerged as potential alternatives to conventional randomized controlled trials (RCTs). While RCTs remain the gold standard for estimating treatment effects, in some contexts, such as rare diseases, it is infeasible or unethical to enroll and randomize a sufficient number of patients. In such cases, it may be justified to conduct a hybrid or single-arm trial that incorporates EC data. This integration first depends on the harmonization of inclusion criteria, covariates, and outcomes, and then requires appropriate statistical methods that account for differences between the trial and EC patients. The propensity score (PS) has emerged as a valuable tool to summarize such differences in patient characteristics. The PS may contribute to a range of estimation methods, including balancing weights, augmented estimators, and Bayesian methods for dynamic borrowing. However, in the context of trials with ECs, the interpretation of the PS and associated causal estimands is often unclear. Motivated by the LIMIT-JIA trial of juvenile idiopathic arthritis, we elucidate potential estimands and evaluate the performance of PS-weighted estimators. We show that some estimands are easier to estimate than others, with potentially greater feasibility for small studies like LIMIT-JIA.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"162 ","pages":"Article 108220"},"PeriodicalIF":1.9,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145963091","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 : 2026-01-13DOI: 10.1016/j.cct.2026.108222
D. Brad Rindal, Stephen Asche, Elyse Kharbanda, Bryan Michalowicz, Don Worley, Meghan Jaka, Kay Kromrey, Linda Fletcher, Amanda Gillesby, Sarah Basile, Patricia L. Mabry
Background
Human papillomavirus is a prevalent DNA virus and the leading cause of both oropharyngeal and cervical cancer. Despite the availability of an effective vaccine (HPV-V), uptake is below national targets. A behavioral intervention, Increasing HPV Vaccine Uptake – Delivered in Dental Settings (HPV-V Uptake-DDS), was developed to support dental providers in promoting HPV-V to their patients to help close this gap.
Objectives
This protocol for an efficacy trial of HPV-V Uptake-DDS is designed to increase HPV-V promotion by dental practitioners, and subsequent vaccine uptake among adolescent and young adult patients.
Methods
The trial will be conducted in dental clinics in a single midwestern health system utilizing a prospective, two-arm, parallel, cluster-randomized controlled design. Eighteen clinics will be randomly assigned to either the intervention or usual care. The intervention includes didactic training, clinical decision support tool embedded in the electronic dental record, tip sheet, patient education handout, and practitioner performance reports. The primary outcome is change in HPV-V promotion by practitioners. Secondary outcomes include change in HPV-V uptake by patients and changes in three behavioral mechanisms: practitioner knowledge, self-efficacy, and fear of negative consequences related to HPV-V promotion. Outcomes will be captured from the electronic health record, practitioner surveys, patient or guardian surveys, and state vaccination registries.
Conclusions
The protocol for a clinical trial will test the efficacy of the intervention and the measurement of behavioral mechanisms of action will inform which components of the intervention of needed to address barriers in different practice settings.
{"title":"Increasing HPV vaccine promotion by dental providers: A clinical trial protocol","authors":"D. Brad Rindal, Stephen Asche, Elyse Kharbanda, Bryan Michalowicz, Don Worley, Meghan Jaka, Kay Kromrey, Linda Fletcher, Amanda Gillesby, Sarah Basile, Patricia L. Mabry","doi":"10.1016/j.cct.2026.108222","DOIUrl":"10.1016/j.cct.2026.108222","url":null,"abstract":"<div><h3>Background</h3><div>Human papillomavirus is a prevalent DNA virus and the leading cause of both oropharyngeal and cervical cancer. Despite the availability of an effective vaccine (HPV-V), uptake is below national targets. A behavioral intervention, Increasing HPV Vaccine Uptake – Delivered in Dental Settings (HPV-V Uptake-DDS), was developed to support dental providers in promoting HPV-V to their patients to help close this gap.</div></div><div><h3>Objectives</h3><div>This protocol for an efficacy trial of HPV-V Uptake-DDS is designed to increase HPV-V promotion by dental practitioners, and subsequent vaccine uptake among adolescent and young adult patients.</div></div><div><h3>Methods</h3><div>The trial will be conducted in dental clinics in a single midwestern health system utilizing a prospective, two-arm, parallel, cluster-randomized controlled design. Eighteen clinics will be randomly assigned to either the intervention or usual care. The intervention includes didactic training, clinical decision support tool embedded in the electronic dental record, tip sheet, patient education handout, and practitioner performance reports. The primary outcome is change in HPV-V promotion by practitioners. Secondary outcomes include change in HPV-V uptake by patients and changes in three behavioral mechanisms: practitioner knowledge, self-efficacy, and fear of negative consequences related to HPV-V promotion. Outcomes will be captured from the electronic health record, practitioner surveys, patient or guardian surveys, and state vaccination registries.</div></div><div><h3>Conclusions</h3><div>The protocol for a clinical trial will test the efficacy of the intervention and the measurement of behavioral mechanisms of action will inform which components of the intervention of needed to address barriers in different practice settings.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"162 ","pages":"Article 108222"},"PeriodicalIF":1.9,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976431","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 : 2026-01-13DOI: 10.1016/j.cct.2026.108224
Hannah E Reese, W Alan Brown, Yaerin H Wallenberger, Kesley A Ramsey, Lauren E Browning, Joshua Rooks, Neda F Gould, Jeannie-Marie Leoutsakos, Tamar Mendelson, Alexandria H Chang, Joseph F McGuire
Tourette Syndrome and persistent tic disorders (collectively, TS) are characterized by involuntary motor and/or vocal tics that onset in childhood. Existing evidence-based treatments-including behavior therapy and pharmacotherapy-are often only partially effective, associated with burdensome side effects, and/or inaccessible. The current paper describes a randomized controlled trial designed to compare a novel, remotely delivered mindfulness-based group intervention for tics (MBIT) to psychoeducation with relaxation and supportive therapy (PRST) in 150 adults with TS. All interventions and assessments will be delivered remotely using secure telehealth platforms and online electronic data capture systems. An independent evaluator masked to treatment condition will administer all tic assessments. The primary aims of the study are to: 1) examine the efficacy of MBIT relative to PRST for tic severity and 2) investigate the mechanism by which MBIT reduces tic severity. Additional aims include: 1) examination of secondary outcomes (e.g., comorbid conditions, quality of life), and 2) exploration of the durability of any observed improvements over a 6-month follow-up. Findings have the potential to meaningfully expand the range of evidence-based treatment options available to adults with TS.
{"title":"Remote delivery of a mindfulness-based intervention for adults with tics: Protocol of a randomized controlled trial.","authors":"Hannah E Reese, W Alan Brown, Yaerin H Wallenberger, Kesley A Ramsey, Lauren E Browning, Joshua Rooks, Neda F Gould, Jeannie-Marie Leoutsakos, Tamar Mendelson, Alexandria H Chang, Joseph F McGuire","doi":"10.1016/j.cct.2026.108224","DOIUrl":"https://doi.org/10.1016/j.cct.2026.108224","url":null,"abstract":"<p><p>Tourette Syndrome and persistent tic disorders (collectively, TS) are characterized by involuntary motor and/or vocal tics that onset in childhood. Existing evidence-based treatments-including behavior therapy and pharmacotherapy-are often only partially effective, associated with burdensome side effects, and/or inaccessible. The current paper describes a randomized controlled trial designed to compare a novel, remotely delivered mindfulness-based group intervention for tics (MBIT) to psychoeducation with relaxation and supportive therapy (PRST) in 150 adults with TS. All interventions and assessments will be delivered remotely using secure telehealth platforms and online electronic data capture systems. An independent evaluator masked to treatment condition will administer all tic assessments. The primary aims of the study are to: 1) examine the efficacy of MBIT relative to PRST for tic severity and 2) investigate the mechanism by which MBIT reduces tic severity. Additional aims include: 1) examination of secondary outcomes (e.g., comorbid conditions, quality of life), and 2) exploration of the durability of any observed improvements over a 6-month follow-up. Findings have the potential to meaningfully expand the range of evidence-based treatment options available to adults with TS.</p>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":" ","pages":"108224"},"PeriodicalIF":1.9,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988542","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 : 2026-01-09DOI: 10.1016/j.cct.2026.108218
Arianna Morel , Emerson Delacroix , John D. Rice , Sarah Austin , Erika Koeppe , Erika N. Hanson , Jennifer J. Griggs , Elena Martinez Stoffel , Ken Resnicow
Background
Participant recruitment remains a significant challenge in clinical trials, often resulting in delays, increased resource expenditures, and missed opportunities for advancing care. While previous research has largely focused on participants' perspectives regarding recruitment barriers, less is known about the influence of different outreach strategies (methods and frequency) from the viewpoint of research staff. This study evaluates the likelihood of reaching a definitive enrollment outcome to inform more effective and resource-efficient recruitment strategies.
Methods
Data were obtained from recruitment efforts for a two-phase clinical trial aimed at increasing hereditary cancer genetic testing uptake among eligible individuals. Participant recruitment utilized email invitations for patients in participating practices and multimedia campaigns for the public. Eligible participants received up to two email reminders and 5–8 recruitment calls, with a standardized call survey ensuring consistency.
Results
Of the invited, 2485 (82.8%) accessed the email link and completed the eligibility screening survey, of these 80.4% of invitees reached a definitive recruitment status outcome: ineligible (37.2%), refused (15.6%), consented (27.6%), while 19.5% were lost to enrollment. Analysis of call attempts revealed that call attempt one had the highest participant answer rate (∼45%), which declined with each additional attempt, reaching 13% at six or more attempts. Email outreach alone produced probability spikes in definitive outcomes following email reminders. Additional calls demonstrated sharply diminishing returns beyond the fourth to sixth attempts.
Conclusion
This study demonstrates that tracking and optimizing outreach frequency, timing, and mode can enhance clinical trial recruitment efficiency. Specifically, at least one email and one phone call significantly improve the likelihood of reaching a definitive recruitment outcome, while exceeding 4–6 call attempts yields minimal additional benefit. These findings provide a framework for recruitment strategies, enabling more effective allocation of resources and increasing the chances of meeting recruitment goals in future clinical trials.
{"title":"Quantifying the role of communication in recruitment status outcomes for a clinical trial on genetic testing uptake","authors":"Arianna Morel , Emerson Delacroix , John D. Rice , Sarah Austin , Erika Koeppe , Erika N. Hanson , Jennifer J. Griggs , Elena Martinez Stoffel , Ken Resnicow","doi":"10.1016/j.cct.2026.108218","DOIUrl":"10.1016/j.cct.2026.108218","url":null,"abstract":"<div><h3>Background</h3><div>Participant recruitment remains a significant challenge in clinical trials, often resulting in delays, increased resource expenditures, and missed opportunities for advancing care. While previous research has largely focused on participants' perspectives regarding recruitment barriers, less is known about the influence of different outreach strategies (methods and frequency) from the viewpoint of research staff. This study evaluates the likelihood of reaching a definitive enrollment outcome to inform more effective and resource-efficient recruitment strategies.</div></div><div><h3>Methods</h3><div>Data were obtained from recruitment efforts for a two-phase clinical trial aimed at increasing hereditary cancer genetic testing uptake among eligible individuals. Participant recruitment utilized email invitations for patients in participating practices and multimedia campaigns for the public. Eligible participants received up to two email reminders and 5–8 recruitment calls, with a standardized call survey ensuring consistency.</div></div><div><h3>Results</h3><div>Of the invited, 2485 (82.8%) accessed the email link and completed the eligibility screening survey, of these 80.4% of invitees reached a definitive recruitment status outcome: ineligible (37.2%), refused (15.6%), consented (27.6%), while 19.5% were lost to enrollment. Analysis of call attempts revealed that call attempt one had the highest participant answer rate (∼45%), which declined with each additional attempt, reaching 13% at six or more attempts. Email outreach alone produced probability spikes in definitive outcomes following email reminders. Additional calls demonstrated sharply diminishing returns beyond the fourth to sixth attempts.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that tracking and optimizing outreach frequency, timing, and mode can enhance clinical trial recruitment efficiency. Specifically, at least one email and one phone call significantly improve the likelihood of reaching a definitive recruitment outcome, while exceeding 4–6 call attempts yields minimal additional benefit. These findings provide a framework for recruitment strategies, enabling more effective allocation of resources and increasing the chances of meeting recruitment goals in future clinical trials.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"161 ","pages":"Article 108218"},"PeriodicalIF":1.9,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145951532","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 : 2026-01-08DOI: 10.1016/j.cct.2026.108219
Caroline Blackwell Young , Emily Rives , Kimberly A. Gudzune , Byron C. Jaeger , Courtney G. Simmons , Brian N. White , Stephanie A. Hooker , Deborah B. Horn , Deborah R. Young , Jennifer Vesely , Amanda Velazquez , Catherine Price , Shelly D. Cook , Katy Martin-Fernandez , Galina Inzhakova , Nicholas M. Pajewski , Jamy D. Ard , Kristina H. Lewis
Background
Current clinical practice guidelines support the long-term use of pharmacotherapy for obesity treatment. Historically, phentermine has been one of the most prescribed obesity medications (OMs), however, its long-term efficacy and safety have never been evaluated in a randomized trial as its market approval predates such requirements. Here we describe the design, rationale, and baseline characteristics for a 24-month, double-blind, randomized controlled trial evaluating the efficacy, cardiovascular risk, and safety of phentermine in adults with overweight or obesity.
Methods
This multicenter trial will compare outcomes among participants randomized to phentermine 24 mg daily versus placebo for 24 months. All participants also receive an online lifestyle intervention. A total of 870 participants with body mass index of 27–44.9 kg/m2 were randomized across six sites in North Carolina (2), Minnesota, Texas, and California (2). Primary outcomes are 24-month mean percent weight loss (efficacy), 24-month mean change in systolic blood pressure (cardiometabolic risk), and overall rates of adverse events and serious adverse events (safety). Secondary outcomes include changes in resting energy expenditure/resting metabolic rate, cardiac autonomic function measured using heart rate variability with electrocardiogram, and a self-reported measure of phentermine dependence.
Conclusions
The safety and efficacy of long-term phentermine remains a pressing, unanswered question, particularly given its low cost and high availability when compared to newer OMs that are highly effective but often associated with significant costs. This study will impact clinical practice regardless of result – either providing evidence to support use of an available low-cost option or prioritizing the use of other OMs.
{"title":"The long-term effectiveness of the anti-obesity medication phentermine (LEAP) trial: Rationale, design, and baseline characteristics","authors":"Caroline Blackwell Young , Emily Rives , Kimberly A. Gudzune , Byron C. Jaeger , Courtney G. Simmons , Brian N. White , Stephanie A. Hooker , Deborah B. Horn , Deborah R. Young , Jennifer Vesely , Amanda Velazquez , Catherine Price , Shelly D. Cook , Katy Martin-Fernandez , Galina Inzhakova , Nicholas M. Pajewski , Jamy D. Ard , Kristina H. Lewis","doi":"10.1016/j.cct.2026.108219","DOIUrl":"10.1016/j.cct.2026.108219","url":null,"abstract":"<div><h3>Background</h3><div>Current clinical practice guidelines support the long-term use of pharmacotherapy for obesity treatment. Historically, phentermine has been one of the most prescribed obesity medications (OMs), however, its long-term efficacy and safety have never been evaluated in a randomized trial as its market approval predates such requirements. Here we describe the design, rationale, and baseline characteristics for a 24-month, double-blind, randomized controlled trial evaluating the efficacy, cardiovascular risk, and safety of phentermine in adults with overweight or obesity.</div></div><div><h3>Methods</h3><div>This multicenter trial will compare outcomes among participants randomized to phentermine 24 mg daily versus placebo for 24 months. All participants also receive an online lifestyle intervention. A total of 870 participants with body mass index of 27–44.9 kg/m<sup>2</sup> were randomized across six sites in North Carolina (2), Minnesota, Texas, and California (2). Primary outcomes are 24-month mean percent weight loss (efficacy), 24-month mean change in systolic blood pressure (cardiometabolic risk), and overall rates of adverse events and serious adverse events (safety). Secondary outcomes include changes in resting energy expenditure/resting metabolic rate, cardiac autonomic function measured using heart rate variability with electrocardiogram, and a self-reported measure of phentermine dependence.</div></div><div><h3>Conclusions</h3><div>The safety and efficacy of long-term phentermine remains a pressing, unanswered question, particularly given its low cost and high availability when compared to newer OMs that are highly effective but often associated with significant costs. This study will impact clinical practice regardless of result – either providing evidence to support use of an available low-cost option or prioritizing the use of other OMs.</div><div><strong>Trial Registration:</strong> Clinicaltrials.gov, NCT05176626.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"161 ","pages":"Article 108219"},"PeriodicalIF":1.9,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948659","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 : 2026-01-07DOI: 10.1016/j.cct.2025.108213
Diana Anena, Elizabeth Chappell, Rashidah Nazzinda, Cecilia Kiilu, Moses Chitsamatanga, Tiyara Arumugam, Alexandra Green, Cissy Kityo Mutuluuza, Mutsa Bwakura-Dangarembizi, Abraham Siika, Moherndran Archary, Lungile Jafta, Stella Namukwaya, Janet Seeley, George Akabwai, Henry Mugerwa, Lisanne Bevers, David Burger, Simon Walker, Alasdair Bamford, Annabelle South, Naomi Apoto, Molly Bush, Margaret J Thomason, Ben Spittle, Deborah Ford, Adeodata R Kekitiinwa, Sarah L Pett
Background: Alternatives to daily oral antiretroviral therapy (ART) are important for adolescents with HIV (AHIV) to improve adherence and outcomes. Long-Acting-injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) has demonstrated excellent efficacy and safety and strong patient preference in adults.
Methods: LATA is an ongoing randomised, open-label, 96-week, non-inferiority trial evaluating the efficacy, safety and acceptability of LAI CAB/RPV vs. daily oral therapy with tenofovir (disoproxil fumarate or alafenamide)/lamivudine/dolutegravir (TLD). Participants are virologically suppressed AHIV aged 12- < 20 years in Kenya/South Africa/Uganda/Zimbabwe. Randomisation was 1:1 to LAI CAB/RPV given once every 8 weeks (after optional oral lead-in) or daily oral TLD. The primary outcome is viral rebound (two consecutive viral loads ≥50 copies/mL by 96-weeks). Viral loads are measured every 24 weeks. The trial employs the Smooth Away From the Expected (SAFE) non-inferiority frontier, where the non-inferiority margin depends on the observed event rate in the control arm. Secondary outcomes include confirmed viral load ≥200 copies/mL by 96-weeks, HIV resistance, safety, patient-reported outcomes and cost-effectiveness. LAI participants return to oral ART at confirmed viral load ≥200 copies/mL; LAI participants who become pregnant are given the choice to continue on LAI or to switch back to daily oral ART, with optional pharmacokinetic sampling during pregnancy and post-partum in both groups. Enrolment of 476 AHIV completed in April 2024. Results will be reported in 2026.
Conclusion: LATA is the first trial comparing the efficacy, safety and acceptability of LAI CAB/RPV to oral ART in AHIV, enrolled in Sub-Saharan Africa, using a programmatic approach to viral load testing.
Trial registration: This trial has been registered with ClinicalTrials.gov (NCT05154747).
{"title":"Trial design and enrolment characteristics of LATA (long-acting treatment in adolescents): A randomised, open-label, non-inferiority, 96-week trial evaluating the virological efficacy, safety, acceptability and quality-of-life of the dual long-acting injectable regimen cabotegravir/ rilpivirine compared to daily oral therapy in virologically suppressed adolescents with HIV-1 infection, aged 12 to <20 years, in Sub-Saharan Africa.","authors":"Diana Anena, Elizabeth Chappell, Rashidah Nazzinda, Cecilia Kiilu, Moses Chitsamatanga, Tiyara Arumugam, Alexandra Green, Cissy Kityo Mutuluuza, Mutsa Bwakura-Dangarembizi, Abraham Siika, Moherndran Archary, Lungile Jafta, Stella Namukwaya, Janet Seeley, George Akabwai, Henry Mugerwa, Lisanne Bevers, David Burger, Simon Walker, Alasdair Bamford, Annabelle South, Naomi Apoto, Molly Bush, Margaret J Thomason, Ben Spittle, Deborah Ford, Adeodata R Kekitiinwa, Sarah L Pett","doi":"10.1016/j.cct.2025.108213","DOIUrl":"https://doi.org/10.1016/j.cct.2025.108213","url":null,"abstract":"<p><strong>Background: </strong>Alternatives to daily oral antiretroviral therapy (ART) are important for adolescents with HIV (AHIV) to improve adherence and outcomes. Long-Acting-injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) has demonstrated excellent efficacy and safety and strong patient preference in adults.</p><p><strong>Methods: </strong>LATA is an ongoing randomised, open-label, 96-week, non-inferiority trial evaluating the efficacy, safety and acceptability of LAI CAB/RPV vs. daily oral therapy with tenofovir (disoproxil fumarate or alafenamide)/lamivudine/dolutegravir (TLD). Participants are virologically suppressed AHIV aged 12- < 20 years in Kenya/South Africa/Uganda/Zimbabwe. Randomisation was 1:1 to LAI CAB/RPV given once every 8 weeks (after optional oral lead-in) or daily oral TLD. The primary outcome is viral rebound (two consecutive viral loads ≥50 copies/mL by 96-weeks). Viral loads are measured every 24 weeks. The trial employs the Smooth Away From the Expected (SAFE) non-inferiority frontier, where the non-inferiority margin depends on the observed event rate in the control arm. Secondary outcomes include confirmed viral load ≥200 copies/mL by 96-weeks, HIV resistance, safety, patient-reported outcomes and cost-effectiveness. LAI participants return to oral ART at confirmed viral load ≥200 copies/mL; LAI participants who become pregnant are given the choice to continue on LAI or to switch back to daily oral ART, with optional pharmacokinetic sampling during pregnancy and post-partum in both groups. Enrolment of 476 AHIV completed in April 2024. Results will be reported in 2026.</p><p><strong>Conclusion: </strong>LATA is the first trial comparing the efficacy, safety and acceptability of LAI CAB/RPV to oral ART in AHIV, enrolled in Sub-Saharan Africa, using a programmatic approach to viral load testing.</p><p><strong>Trial registration: </strong>This trial has been registered with ClinicalTrials.gov (NCT05154747).</p>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":" ","pages":"108213"},"PeriodicalIF":1.9,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145942790","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 : 2026-01-06DOI: 10.1016/j.cct.2026.108216
Muhammad Hammad , Sindhu Shankar , Yan Gao , Jacquelyn Kulinski
Background
Sedentary behavior is an independent risk factor for cardiometabolic disease. With the rise of desk-based occupations and work-from-home culture, the workplace offers a promising setting to employ interventions to reduce sedentary time.
Objective
The goal of this randomized controlled trial is to determine if reducing sedentary time with sit-stand desks improves cardiometabolic health outcomes in overweight and obese individuals with sedentary jobs who are at risk of developing diabetes.
Methods
Approximately 198 eligible participants (includes estimated 25% drop-out) with pre-diabetes or at-risk for type 2 diabetes will be randomized in a 1:1:1 ratio into three groups: a control group (no intervention), a 2-h group (instructed to stand at their sit-stand desks for at least 2 h daily), and a 3-h group (instructed to stand for at least 3 h daily). Each participant will complete three study visits over a 6-month period. The primary outcome is insulin resistance.
Discussion
The potential impact of this study is significant, given that over 70% of the U.S. population is overweight or obese, and more than 80% of jobs are sedentary. Affirmative findings from our study would advance the field by demonstrating that an easily adoptable intervention can reduce cardiometabolic risk, providing justification for widespread implementation of standing desks in the workplace.
Conclusion
This randomized, control study will determine if reducing sedentary behavior at work, with an adjustable sit-stand desk, improves insulin resistance in individuals at risk for diabetes. This study may help inform public health guidelines benefitting a large population of sedentary workers.
{"title":"Stand up for your health: Rationale and design for a randomized controlled trial","authors":"Muhammad Hammad , Sindhu Shankar , Yan Gao , Jacquelyn Kulinski","doi":"10.1016/j.cct.2026.108216","DOIUrl":"10.1016/j.cct.2026.108216","url":null,"abstract":"<div><h3>Background</h3><div>Sedentary behavior is an independent risk factor for cardiometabolic disease. With the rise of desk-based occupations and work-from-home culture, the workplace offers a promising setting to employ interventions to reduce sedentary time.</div></div><div><h3>Objective</h3><div>The goal of this randomized controlled trial is to determine if reducing sedentary time with sit-stand desks improves cardiometabolic health outcomes in overweight and obese individuals with sedentary jobs who are at risk of developing diabetes.</div></div><div><h3>Methods</h3><div>Approximately 198 eligible participants (includes estimated 25% drop-out) with pre-diabetes or at-risk for type 2 diabetes will be randomized in a 1:1:1 ratio into three groups: a control group (no intervention), a 2-h group (instructed to stand at their sit-stand desks for at least 2 h daily), and a 3-h group (instructed to stand for at least 3 h daily). Each participant will complete three study visits over a 6-month period. The primary outcome is insulin resistance.</div></div><div><h3>Discussion</h3><div>The potential impact of this study is significant, given that over 70% of the U.S. population is overweight or obese, and more than 80% of jobs are sedentary. Affirmative findings from our study would advance the field by demonstrating that an easily adoptable intervention can reduce cardiometabolic risk, providing justification for widespread implementation of standing desks in the workplace.</div></div><div><h3>Conclusion</h3><div>This randomized, control study will determine if reducing sedentary behavior at work, with an adjustable sit-stand desk, improves insulin resistance in individuals at risk for diabetes. This study may help inform public health guidelines benefitting a large population of sedentary workers.</div><div>Clinical trial registration identifier: <span><span>NCT05585190</span><svg><path></path></svg></span></div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"161 ","pages":"Article 108216"},"PeriodicalIF":1.9,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922245","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 : 2026-01-05DOI: 10.1016/j.cct.2026.108215
Gabrielle A Brown, William C McCamy, Danielle I King, Anna C Ferriera, Amy E Wahlquist, John Kaczmar, Karen L Cropsey, Matthew J Carpenter, Tracy T Smith
Background: Most attempts to quit smoking cigarettes end in failure, even when FDA-approved pharmacotherapies are used. Despite the frequency of treatment non-response, few trials have investigated the best path forward after treatment failure. This trial will assess two primary aims: 1) determine whether switching pharmacotherapies following initial failure promotes abstinence more effectively than repeated attempts with the same pharmacotherapy, and 2) determine whether switching to e-cigarettes following successive failures with pharmacotherapy promotes abstinence from combustible cigarettes better than continuing with pharmacotherapy.
Methods: Adults in South Carolina and Alabama who smoke daily and are willing to set a quit date will be assigned in a counterbalanced fashion to receive a 4-week supply of FDA approved smoking-cessation medication (either combination nicotine replacement therapy or varenicline) and asked to set a quit date. After four weeks of treatment, treatment non-responders will be assigned in a 2:1 fashion to either switch medications or continue with the same medication (Aim 1). After a second four weeks of treatment, non-responders will be assigned in a 2:1 fashion to either switch to e-cigarettes or continue with the same pharmacotherapy (Aim 2), with outcomes assessed through 6 months (Aim 3). The primary outcome is biochemically confirmed 7-day abstinence from smoking, assessed repeatedly across separate study aims. Secondary outcomes include smoking reduction, nicotine dependence, and duration of abstinence.
Conclusion: This trial is positioned to provide strong, data-driven guidance on treatment decision-making following treatment failure. The trial results will provide a significant opportunity to optimize cessation outcomes for smokers who continue to struggle with quitting.
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Pub Date : 2026-01-03DOI: 10.1016/j.cct.2025.108212
Iris Dalhuisen , Marloes Wurkum , Chris Bervoets , Eric Constant , Eric van Exel , Mickaël Hiligsmann , Alexander Sack , Teresa Schuhmann , Indira Tendolkar , Thierry Verplancke , Ben Wijnen , Chris Baeken , Philip van Eijndhoven
Introduction
Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder (MDD), yet some patients only show partial or no response. Recent efforts to enhance rTMS efficacy have focused on combining rTMS with adjunctive interventions, such as psychotherapy, which may yield synergistic effects rather than merely additive effects. Cognitive control training (CCT) activates similar underlying neural circuits as rTMS and has demonstrated antidepressant potential. Given the time-intensive nature of rTMS, augmenting it with CCT may offer a pragmatic, time-efficient and potentially cost-effective solution to increase the therapeutic response of rTMS. This study aims to investigate whether rTMS augmented with CCT is more (cost-) effective in reducing depressive symptoms as opposed to rTMS alone.
Methods
In this international multicenter clinical trial, 132 adult patients with depression will be randomized to receive rTMS either augmented with CCT or placebo task. The trial consists 30 rTMS sessions over eight weeks, followed by a follow-up period up to one year. The primary outcome is the change in depressive severity, assessed with the 17-item Hamilton Depression Rating Scale (HDRS-17) after eight weeks of treatment. Secondary outcomes include an economic evaluation and response and remission after 8 weeks of treatment as well as during follow-up.
Discussion
The present study aims to improve the (cost-)effectiveness of rTMS by concurrently combining rTMS with CCT. Findings may support the development of more cost-effective, personalized interventions for the treatment of depression.
Trial registration
This trial is registered within the Overview of medical research in the Netherlands, OMON (code: NL-OMON57187, date: 18 December 2024).
{"title":"Enhancing effect of cognitive control training on rTMS treatment in depression: A study protocol for a multicenter randomized controlled trial","authors":"Iris Dalhuisen , Marloes Wurkum , Chris Bervoets , Eric Constant , Eric van Exel , Mickaël Hiligsmann , Alexander Sack , Teresa Schuhmann , Indira Tendolkar , Thierry Verplancke , Ben Wijnen , Chris Baeken , Philip van Eijndhoven","doi":"10.1016/j.cct.2025.108212","DOIUrl":"10.1016/j.cct.2025.108212","url":null,"abstract":"<div><h3>Introduction</h3><div>Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder (MDD), yet some patients only show partial or no response. Recent efforts to enhance rTMS efficacy have focused on combining rTMS with adjunctive interventions, such as psychotherapy, which may yield synergistic effects rather than merely additive effects. Cognitive control training (CCT) activates similar underlying neural circuits as rTMS and has demonstrated antidepressant potential. Given the time-intensive nature of rTMS, augmenting it with CCT may offer a pragmatic, time-efficient and potentially cost-effective solution to increase the therapeutic response of rTMS. This study aims to investigate whether rTMS augmented with CCT is more (cost-) effective in reducing depressive symptoms as opposed to rTMS alone.</div></div><div><h3>Methods</h3><div>In this international multicenter clinical trial, 132 adult patients with depression will be randomized to receive rTMS either augmented with CCT or placebo task. The trial consists 30 rTMS sessions over eight weeks, followed by a follow-up period up to one year. The primary outcome is the change in depressive severity, assessed with the 17-item Hamilton Depression Rating Scale (HDRS-17) after eight weeks of treatment. Secondary outcomes include an economic evaluation and response and remission after 8 weeks of treatment as well as during follow-up.</div></div><div><h3>Discussion</h3><div>The present study aims to improve the (cost-)effectiveness of rTMS by concurrently combining rTMS with CCT. Findings may support the development of more cost-effective, personalized interventions for the treatment of depression.</div></div><div><h3>Trial registration</h3><div>This trial is registered within the Overview of medical research in the Netherlands, OMON (code: NL-OMON57187, date: 18 December 2024).</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"161 ","pages":"Article 108212"},"PeriodicalIF":1.9,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145905728","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 : 2026-01-02DOI: 10.1016/j.cct.2025.108214
Jaime Perales-Puchalt , Mariana Ramírez-Mantilla , Henry P. Moore , Idaly Velez-Uribe , Vanessa Sepulveda-Rivera , Rachel Ruiz , Mónica Fracachán-Cabrera , Yesenia Herrera , Christina Baker , Antonio Miras-Neira , Becky Bothwell , Heidi Anderson , Tina Lewandowski , Francisco J. Diaz , K. Allen Greiner , Kristine Williams , Eric D. Vidoni , Edward Ellerbeck , Jeffrey M. Burns
Background
Latino caregivers have poor mental health and access to caregiver support services. Here, we describe the protocol for a randomized controlled trial (RCT) to evaluate the effect of a text message intervention on depression and distress among informal Latino dementia caregivers. We will also assess mechanisms of action.
Methods
We are enrolling 288 Latino dementia informal caregivers 18 or older into a parallel group RCT. Participants randomized to the intervention group receive a remote, asynchronous, bilingual, bi-directional, 6-month texting program focused on dementia education, skill-building and community resources. The control group enters a 7-month waitlist after which they are offered the same intervention as the intervention group. Randomization is stratified by each of the four recruitment sites at a 1:1 ratio. Outcomes (e.g., caregiver depressive symptomatology, distress) are measured via surveys at baseline, 3, 6 and 7 months.
Conclusions
This RCT addresses two priority areas: eliminating dementia disparities and optimizing caregiver support. Findings have the potential to make clinical and policy-relevant contributions by providing appropriate caregiver support to Latinos in a highly scalable way.
{"title":"Testing the effects of a text message intervention on depression and distress among Latino dementia caregivers: A randomized controlled trial protocol","authors":"Jaime Perales-Puchalt , Mariana Ramírez-Mantilla , Henry P. Moore , Idaly Velez-Uribe , Vanessa Sepulveda-Rivera , Rachel Ruiz , Mónica Fracachán-Cabrera , Yesenia Herrera , Christina Baker , Antonio Miras-Neira , Becky Bothwell , Heidi Anderson , Tina Lewandowski , Francisco J. Diaz , K. Allen Greiner , Kristine Williams , Eric D. Vidoni , Edward Ellerbeck , Jeffrey M. Burns","doi":"10.1016/j.cct.2025.108214","DOIUrl":"10.1016/j.cct.2025.108214","url":null,"abstract":"<div><h3>Background</h3><div>Latino caregivers have poor mental health and access to caregiver support services. Here, we describe the protocol for a randomized controlled trial (RCT) to evaluate the effect of a text message intervention on depression and distress among informal Latino dementia caregivers. We will also assess mechanisms of action.</div></div><div><h3>Methods</h3><div>We are enrolling 288 Latino dementia informal caregivers 18 or older into a parallel group RCT. Participants randomized to the intervention group receive a remote, asynchronous, bilingual, bi-directional, 6-month texting program focused on dementia education, skill-building and community resources. The control group enters a 7-month waitlist after which they are offered the same intervention as the intervention group. Randomization is stratified by each of the four recruitment sites at a 1:1 ratio. Outcomes (e.g., caregiver depressive symptomatology, distress) are measured via surveys at baseline, 3, 6 and 7 months.</div></div><div><h3>Conclusions</h3><div>This RCT addresses two priority areas: eliminating dementia disparities and optimizing caregiver support. Findings have the potential to make clinical and policy-relevant contributions by providing appropriate caregiver support to Latinos in a highly scalable way.</div><div>Protocol version/date: 1/14/2025.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"161 ","pages":"Article 108214"},"PeriodicalIF":1.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145899342","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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