Pub Date : 2026-02-01Epub Date: 2025-12-15DOI: 10.1016/j.cct.2025.108184
Diane M. Wisnieski , Rebecca C. Rossom , Lauren M. Weinstock , Jennifer Johnson , Kathleen Miley , Brandon A. Gaudiano , Madeline B. Benz , Caitlin Borgert-Spaniol , Hannah R. Graves , Rachael Norwood , Rowyda Kazan , Colleen Starkey , Hanmin Kim , Linda Fletcher , Sheryl Kane , Yong Hu , Zachary Farrell , Sarah Strong , Hsueh-Han Yeh , Ted Miller , Brian K. Ahmedani
Background
Over 20 % of all adult suicide deaths in the U.S. occur within one year following jail release. Individuals may have increased access to lethal means, be faced with numerous financial, legal, and social stressors, and encounter a resurgence of legal problems. Suicide prevention interventions have demonstrated effects. Widespread implementation of these interventions for individuals leaving jail detention could have a significant impact on national suicide rates.
Methods
The 5S Study (Syncing, Screening, and Services for Suicide Prevention among Health & Jail Systems) aims to prevent suicide attempts among adults aged 18+ who are recently released from jail. Data from public jail release reports are synced with electronic health record (EHR) systems to enable proactive health system outreach. Those randomized to the intervention are contacted and consented, undergo a suicide risk screening and create a safety plan. Care Coordinators connect participants to health services. High risk participants, identified by the Patient Health Questionnaire (PHQ-9), are offered the Coping Long Term with Active Suicide Program (CLASP), an evidence-based suicide prevention intervention. Those randomized to control are never contacted and receive usual care. There is a waiver of consent for the control condition and a waiver of written consent for the intervention condition.
Discussion
The 5S Study uses data linkage between EHRs and jails to identify and connect with those recently released from jail, a population historically at high risk. Trial results will highlight best practices for syncing these data and offering support during the transition back to the community.
{"title":"Study protocol for a type I hybrid effectiveness trial of strategies to prevent suicide attempts among adults recently released from jail","authors":"Diane M. Wisnieski , Rebecca C. Rossom , Lauren M. Weinstock , Jennifer Johnson , Kathleen Miley , Brandon A. Gaudiano , Madeline B. Benz , Caitlin Borgert-Spaniol , Hannah R. Graves , Rachael Norwood , Rowyda Kazan , Colleen Starkey , Hanmin Kim , Linda Fletcher , Sheryl Kane , Yong Hu , Zachary Farrell , Sarah Strong , Hsueh-Han Yeh , Ted Miller , Brian K. Ahmedani","doi":"10.1016/j.cct.2025.108184","DOIUrl":"10.1016/j.cct.2025.108184","url":null,"abstract":"<div><h3>Background</h3><div>Over 20 % of all adult suicide deaths in the U.S. occur within one year following jail release. Individuals may have increased access to lethal means, be faced with numerous financial, legal, and social stressors, and encounter a resurgence of legal problems. Suicide prevention interventions have demonstrated effects. Widespread implementation of these interventions for individuals leaving jail detention could have a significant impact on national suicide rates.</div></div><div><h3>Methods</h3><div>The 5S Study (Syncing, Screening, and Services for Suicide Prevention among Health & Jail Systems) aims to prevent suicide attempts among adults aged 18+ who are recently released from jail. Data from public jail release reports are synced with electronic health record (EHR) systems to enable proactive health system outreach. Those randomized to the intervention are contacted and consented, undergo a suicide risk screening and create a safety plan. Care Coordinators connect participants to health services. High risk participants, identified by the Patient Health Questionnaire (PHQ-9), are offered the Coping Long Term with Active Suicide Program (CLASP), an evidence-based suicide prevention intervention. Those randomized to control are never contacted and receive usual care. There is a waiver of consent for the control condition and a waiver of written consent for the intervention condition.</div></div><div><h3>Discussion</h3><div>The 5S Study uses data linkage between EHRs and jails to identify and connect with those recently released from jail, a population historically at high risk. Trial results will highlight best practices for syncing these data and offering support during the transition back to the community.</div><div><strong>Trial Registration</strong>: <span><span>https://clinicaltrials.gov/study/NCT06506344</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"161 ","pages":"Article 108184"},"PeriodicalIF":1.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760862","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 : 2026-02-01Epub 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":"2026-02-01","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 : 2026-02-01Epub Date: 2025-12-24DOI: 10.1016/j.cct.2025.108206
Shannon K. Runge , Elizabeth M. Hudak , Jade A. Sutfin , Victor R. Dobrovolskiy , Jerri D. Edwards
Background/Purpose
Participant engagement such as intervention adherence and study retention are critical to evaluating treatment efficacy and clinical trial success. Investigations of navigators among patients with chronic illness report improved health-related outcomes; however, little is known about the effects of navigators in healthy populations or on participant engagement in clinical trials. The purpose of this study was to explore whether peer navigators – former study participants – enhanced intervention adherence or study retention in a clinical trial among healthy older adults.
Methods
We conducted a study within a randomized clinical trial (SWAT) among community-dwelling older adults (N = 268) by assigning a subsample of participants to peer navigators (n = 36). Six former trial participants served as peer navigators. Statistical analyses explored whether navigator assignment was associated with intervention adherence or study retention.
Results
Participants assigned to a navigator were not different from the overall trial sample and were, on average, 71 years of age (SD = 5) with 16 years of education (SD = 3); 56 % identified as female, 81 % as White, and 3 % as Hispanic. Navigator assignment was associated with better intervention adherence, t(134.2) = −6.0, p < .001; participants with a navigator completed an average of 5 more sessions (M = 20, SD = 3) compared to those without a navigator (M = 15, SD = 8). Retention was higher among navigator-assigned participants (100 % vs. 76 %), X2 (1, N = 261) = 10.0, p = .002.
Conclusions
Peer navigators may improve intervention adherence and study retention among older adults in clinical trials. Results suggest that personalized support by a peer may enhance participant engagement in clinical trials, but replication is needed.
The data are from the registered clinical trial: Interventions to Attenuate Cognitive Decline, https://clinicaltrials.gov/study/NCT03528486
{"title":"The influence of peer navigators on intervention adherence and retention among older adults: A study within a randomized trial - SWAT","authors":"Shannon K. Runge , Elizabeth M. Hudak , Jade A. Sutfin , Victor R. Dobrovolskiy , Jerri D. Edwards","doi":"10.1016/j.cct.2025.108206","DOIUrl":"10.1016/j.cct.2025.108206","url":null,"abstract":"<div><h3>Background/Purpose</h3><div>Participant engagement such as intervention adherence and study retention are critical to evaluating treatment efficacy and clinical trial success. Investigations of navigators among patients with chronic illness report improved health-related outcomes; however, little is known about the effects of navigators in healthy populations or on participant engagement in clinical trials. The purpose of this study was to explore whether peer navigators – former study participants – enhanced intervention adherence or study retention in a clinical trial among healthy older adults.</div></div><div><h3>Methods</h3><div>We conducted a study within a randomized clinical trial (SWAT) among community-dwelling older adults (<em>N</em> = 268) by assigning a subsample of participants to peer navigators (<em>n</em> = 36). Six former trial participants served as peer navigators. Statistical analyses explored whether navigator assignment was associated with intervention adherence or study retention.</div></div><div><h3>Results</h3><div>Participants assigned to a navigator were not different from the overall trial sample and were, on average, 71 years of age (<em>SD</em> = 5) with 16 years of education (<em>SD</em> = 3); 56 % identified as female, 81 % as White, and 3 % as Hispanic. Navigator assignment was associated with better intervention adherence, <em>t</em>(134.2) = −6.0, <em>p</em> < .001; participants with a navigator completed an average of 5 more sessions (<em>M</em> = 20, <em>SD</em> = 3) compared to those without a navigator (<em>M</em> = 15, <em>SD</em> = 8). Retention was higher among navigator-assigned participants (100 % vs. 76 %), <em>X</em><sup>2</sup> (1, <em>N</em> = 261) = 10.0, <em>p</em> = .002.</div></div><div><h3>Conclusions</h3><div>Peer navigators may improve intervention adherence and study retention among older adults in clinical trials. Results suggest that personalized support by a peer may enhance participant engagement in clinical trials, but replication is needed.</div><div>The data are from the registered clinical trial: Interventions to Attenuate Cognitive Decline, <span><span>https://clinicaltrials.gov/study/NCT03528486</span><svg><path></path></svg></span></div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"161 ","pages":"Article 108206"},"PeriodicalIF":1.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843537","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 : 2026-02-01Epub 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":"2026-02-01","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}
Pub Date : 2026-02-01Epub Date: 2025-12-15DOI: 10.1016/j.cct.2025.108187
Danielle M. McCarthy , Lisa B. VanWagner , Miriam R. Rafferty , Kenzie A. Cameron , Jungwha Lee , Siyuan Dong , Anuva Fellner , Amy V. Kontrick
Background
Up to a quarter of emergency department (ED) patients have incidental hepatic steatosis (fatty liver) noted on imaging studies; however, patients are infrequently notified about this new finding. This lack of communication may have consequences including delayed diagnosis of metabolic associated steatotic liver disease (MASLD) and disease progression.
Methods
This type-2 hybrid effectiveness-implementation study uses a Stepped Wedge-Cluster Randomized Trial design across 11 EDs to evaluate an electronic health record (EHR) delivered intervention. The STeatosis Identification, Risk stratification, and Referral pathway in the ED (STIRRED) clinical decision support system leverages the EHR to identify cases of hepatic steatosis and deliver risk-stratified communication to clinicians supporting patient notification about hepatic steatosis in the ED. The primary effectiveness outcome will be receipt of a new steatotic liver disease-related diagnosis among high-risk patients within 120 days post-ED discharge; the primary implementation outcome is fidelity, defined as the degree to which STIRRED was delivered as intended. Over the study period, ∼4700 patients with incidental hepatic steatosis will be analyzed, including 616 high-risk patients, providing 80 % power to detect a risk difference of 5.6 % (odds ratio of 3.5) between STIRRED and usual care in the receipt of a new steatotic liver disease-related diagnosis.
Discussion
This trial uses the electronic health record to deliver an evidence-based risk stratification score and referral recommendation to the bedside clinician in patients with incidentally noted hepatic steatosis. Rigorous implementation science methodology used in both the intervention development and assessment will increase the usability of the intervention and future scalability.
Trial Registration: This trial was prospectively registered on 10/9/2024 with ClinicalTrials.gov (# NCT06944353).
{"title":"Improving diagnostic safety through steatosis identification, risk stratification, and referral pathway in the ED (STIRRED): Protocol for an effectiveness implementation trial","authors":"Danielle M. McCarthy , Lisa B. VanWagner , Miriam R. Rafferty , Kenzie A. Cameron , Jungwha Lee , Siyuan Dong , Anuva Fellner , Amy V. Kontrick","doi":"10.1016/j.cct.2025.108187","DOIUrl":"10.1016/j.cct.2025.108187","url":null,"abstract":"<div><h3>Background</h3><div>Up to a quarter of emergency department (ED) patients have incidental hepatic steatosis (fatty liver) noted on imaging studies; however, patients are infrequently notified about this new finding. This lack of communication may have consequences including delayed diagnosis of metabolic associated steatotic liver disease (MASLD) and disease progression.</div></div><div><h3>Methods</h3><div>This type-2 hybrid effectiveness-implementation study uses a Stepped Wedge-Cluster Randomized Trial design across 11 EDs to evaluate an electronic health record (EHR) delivered intervention. The STeatosis Identification, Risk stratification, and Referral pathway in the ED (STIRRED) clinical decision support system leverages the EHR to identify cases of hepatic steatosis and deliver risk-stratified communication to clinicians supporting patient notification about hepatic steatosis in the ED. The primary effectiveness outcome will be receipt of a new steatotic liver disease-related diagnosis among high-risk patients within 120 days post-ED discharge; the primary implementation outcome is fidelity, defined as the degree to which STIRRED was delivered as intended. Over the study period, ∼4700 patients with incidental hepatic steatosis will be analyzed, including 616 high-risk patients, providing 80 % power to detect a risk difference of 5.6 % (odds ratio of 3.5) between STIRRED and usual care in the receipt of a new steatotic liver disease-related diagnosis.</div></div><div><h3>Discussion</h3><div>This trial uses the electronic health record to deliver an evidence-based risk stratification score and referral recommendation to the bedside clinician in patients with incidentally noted hepatic steatosis. Rigorous implementation science methodology used in both the intervention development and assessment will increase the usability of the intervention and future scalability.</div><div>Trial Registration: This trial was prospectively registered on 10/9/2024 with <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (# <span><span>NCT06944353</span><svg><path></path></svg></span>).</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"161 ","pages":"Article 108187"},"PeriodicalIF":1.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773884","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 : 2026-02-01Epub Date: 2025-12-19DOI: 10.1016/j.cct.2025.108189
Paola Palombo , Nicole Akana , Abigail Bowen , Alex Schmidt , Rachel Ryan , Sean Hovland , B. Connor Stark , Nicole Rodin , Naomi Chaytor , Michael G. McDonell , Ekaterina Burduli , Matthew Layton , John M. Roll , Crystal L. Smith , André Q. Miguel , Sterling M. McPherson
Background
Alcohol and tobacco are often used together, and their co-use is directly associated with a high incidence of morbidity and mortality. While there are currently no guidelines for treating co-addiction to alcohol and tobacco, studies suggest that integrated approaches may effectively reduce the use of both substances. Grounded in the Addiction Neuroclinical Assessment (ANA) framework, this study aims to evaluate the effectiveness of combining Contingency Management (CM) for Alcohol Use Disorder (AUD) with Varenicline for smoking cessation to significantly reduce alcohol and tobacco use among individuals with an AUD who smoke and are seeking treatment. In addition, the study will evaluate the mediator effect of the ANA domains, systematically measured and evaluated to determine their role in treatment outcomes.
Methods
Study will take place in Spokane-WA. After a two-week induction period, a total of 205 eligible participants will be randomized into one of two 12-week treatment conditions in equal proportions: CM + varenicline (experimental condition) and Non-Contingent (NC) + varenicline (control condition). Participants in the CM + varenicline group will receive rewards contingent on the submission of negative alcohol samples, while the NC + varenicline group will receive rewards for submitting urine samples, independent of alcohol positivity. Primary outcomes include objective verification of abstinence during the 12-week intervention phase (measured thrice-weekly). Follow-up evaluations will be conducted during the first, third, and sixth months.
Conclusions
If demonstrated to be efficacious, this treatment approach has the potential to produce important health benefits for a highly prevalent population in desperate need for an integrated treatment. It may also assist in identifying how different ANA-based responses impact treatment outcomes.
{"title":"The pharmaceutically enhanced reinforcement for reduced alcohol and smoking (PERRAS) study: Protocol for a randomized clinical trial","authors":"Paola Palombo , Nicole Akana , Abigail Bowen , Alex Schmidt , Rachel Ryan , Sean Hovland , B. Connor Stark , Nicole Rodin , Naomi Chaytor , Michael G. McDonell , Ekaterina Burduli , Matthew Layton , John M. Roll , Crystal L. Smith , André Q. Miguel , Sterling M. McPherson","doi":"10.1016/j.cct.2025.108189","DOIUrl":"10.1016/j.cct.2025.108189","url":null,"abstract":"<div><h3>Background</h3><div>Alcohol and tobacco are often used together, and their co-use is directly associated with a high incidence of morbidity and mortality. While there are currently no guidelines for treating co-addiction to alcohol and tobacco, studies suggest that integrated approaches may effectively reduce the use of both substances. Grounded in the Addiction Neuroclinical Assessment (ANA) framework, this study aims to evaluate the effectiveness of combining Contingency Management (CM) for Alcohol Use Disorder (AUD) with Varenicline for smoking cessation to significantly reduce alcohol and tobacco use among individuals with an AUD who smoke and are seeking treatment. In addition, the study will evaluate the mediator effect of the ANA domains, systematically measured and evaluated to determine their role in treatment outcomes.</div></div><div><h3>Methods</h3><div>Study will take place in Spokane-WA. After a two-week induction period, a total of 205 eligible participants will be randomized into one of two 12-week treatment conditions in equal proportions: CM + varenicline (experimental condition) and Non-Contingent (NC) + varenicline (control condition). Participants in the CM + varenicline group will receive rewards contingent on the submission of negative alcohol samples, while the NC + varenicline group will receive rewards for submitting urine samples, independent of alcohol positivity. Primary outcomes include objective verification of abstinence during the 12-week intervention phase (measured thrice-weekly). Follow-up evaluations will be conducted during the first, third, and sixth months.</div></div><div><h3>Conclusions</h3><div>If demonstrated to be efficacious, this treatment approach has the potential to produce important health benefits for a highly prevalent population in desperate need for an integrated treatment. It may also assist in identifying how different ANA-based responses impact treatment outcomes.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"161 ","pages":"Article 108189"},"PeriodicalIF":1.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145803361","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 : 2026-02-01Epub 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":"2026-02-01","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 : 2026-02-01Epub Date: 2025-12-05DOI: 10.1016/j.cct.2025.108173
Aseel El Zein , Vishnu Garla , Michael E. Hall , Tanjila Nawshin , Druss Hays , Tejossy John , Erin Delaney , Eric Wallace , Larry Hearld , Andrea L. Cherrington , Tapan Mehta
Background
In the U.S. Deep South, Black adults experience disproportionate rates of type 2 diabetes (T2D) and associated complications, driven in part by adverse social determinants of health (SDoH). Addressing these disparities requires multilevel interventions that can be optimized for both effectiveness and cost. The Food Delivery, Remote Monitoring, & Coaching-Enhanced Education for Optimized Diabetes Management (FREEDOM) trial aims to identify an optimized, scalable intervention package that improves glycemic control among Black adults with T2D.
Methods
FREEDOM is a multicenter, hybrid type 1 optimization-implementation trial uses a 2 × 2 × 2 factorial design to test three intervention components—digital health coaching, food box delivery, and remote patient monitoring (RPM)—among 304 adults recruited from three health systems in Alabama and Mississippi. Interventions are delivered over six months with follow-up assessments through 12 months. The primary clinical outcome is change in HbA1c at 12 months. Secondary outcomes include within-trial cost-utility using net monetary benefit, RE-AIM outcomes, and CFIR-guided qualitative assessment of contextual determinants. Mixed methods will evaluate fidelity and context. Optimization will be determined using the net monetary benefit framework based on quality-adjusted life years (QALYs).
Discussion
This protocol describes the design and methods of the FREEDOM trial, which seeks to address key gaps in optimizing multilevel interventions for adults with T2D in underserved regions of the Deep South. Findings will guide the selection of scalable, cost-effective intervention strategies to improve glycemic control among adults with T2D.
Registration
ClinicalTrials.gov identifier: NCT05288452; first posted December 29, 2022.
{"title":"Rationale and design of the FREEDOM study: A hybrid type 1 optimization-implementation trial to improve type 2 diabetes management in primary care","authors":"Aseel El Zein , Vishnu Garla , Michael E. Hall , Tanjila Nawshin , Druss Hays , Tejossy John , Erin Delaney , Eric Wallace , Larry Hearld , Andrea L. Cherrington , Tapan Mehta","doi":"10.1016/j.cct.2025.108173","DOIUrl":"10.1016/j.cct.2025.108173","url":null,"abstract":"<div><h3>Background</h3><div>In the U.S. Deep South, Black adults experience disproportionate rates of type 2 diabetes (T2D) and associated complications, driven in part by adverse social determinants of health (SDoH). Addressing these disparities requires multilevel interventions that can be optimized for both effectiveness and cost. The Food Delivery, Remote Monitoring, & Coaching-Enhanced Education for Optimized Diabetes Management (FREEDOM) trial aims to identify an optimized, scalable intervention package that improves glycemic control among Black adults with T2D.</div></div><div><h3>Methods</h3><div>FREEDOM is a multicenter, hybrid type 1 optimization-implementation trial uses a 2 × 2 × 2 factorial design to test three intervention components—digital health coaching, food box delivery, and remote patient monitoring (RPM)—among 304 adults recruited from three health systems in Alabama and Mississippi. Interventions are delivered over six months with follow-up assessments through 12 months. The primary clinical outcome is change in HbA1c at 12 months. Secondary outcomes include within-trial cost-utility using net monetary benefit, RE-AIM outcomes, and CFIR-guided qualitative assessment of contextual determinants. Mixed methods will evaluate fidelity and context. Optimization will be determined using the net monetary benefit framework based on quality-adjusted life years (QALYs).</div></div><div><h3>Discussion</h3><div>This protocol describes the design and methods of the FREEDOM trial, which seeks to address key gaps in optimizing multilevel interventions for adults with T2D in underserved regions of the Deep South. Findings will guide the selection of scalable, cost-effective intervention strategies to improve glycemic control among adults with T2D.</div></div><div><h3>Registration</h3><div><span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> identifier: <span><span>NCT05288452</span><svg><path></path></svg></span>; first posted December 29, 2022.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"161 ","pages":"Article 108173"},"PeriodicalIF":1.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145700010","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 : 2026-02-01Epub Date: 2025-12-24DOI: 10.1016/j.cct.2025.108210
Emma L. Tucher , Allison L. Steele , Connie S. Uratsu , Leah K. Hamilton , Meagan C. Brown , Joshua R. Nugent , Danielle Hessler Jones , Laura M. Gottlieb , Richard W. Grant
Background: Adults with multiple chronic conditions (MCC, defined as two plus chronic conditions) account for one-third of the United States population but 71 % of healthcare expenditures. Many adults with MCC also manage social needs like food insecurity or housing instability, which are associated with worse disease outcomes and decreased life expectancy. Research on social needs interventions demonstrated that targeted interventions can significantly improve care utilization and patient well-being. However, many published trials evaluating social needs navigation or resource referrals have focused on a single social need, specific health conditions, or a single intervention strategy.
Methods: This trial (“Addressing Social Needs to Improve Health in Adults with Multiple Chronic Conditions”) is a comparative-effectiveness randomized control trial (CE-RCT) comparing the clinical impact of two commonly implemented social needs interventions (“higher intensity” social needs phone navigation versus “lower intensity” automated electronic resource outreach). It will enroll 12,000 adults with MCC, one or more evidence-based clinical care gaps, and one or more social needs within Kaiser Permanente, an integrated delivery system serving over 12.5 million members. Participants can be randomized to a higher or lower intensity intervention. The primary outcomes are 12-month clinical care gap closures measured via electronic health records, and 6-month receipt of social services and reductions in social needs, measured via patient surveys. Secondary outcomes include survey and interview assessments of stress and experiences of social care.
Conclusion: Results from this CE-RCT provide policy and practice-relevant evidence comparing the impacts of different approaches to addressing social needs in patients with MCC.
{"title":"Addressing social needs to improve health in adults with multiple chronic conditions: A comparative effectiveness trial of two real-world social needs interventions","authors":"Emma L. Tucher , Allison L. Steele , Connie S. Uratsu , Leah K. Hamilton , Meagan C. Brown , Joshua R. Nugent , Danielle Hessler Jones , Laura M. Gottlieb , Richard W. Grant","doi":"10.1016/j.cct.2025.108210","DOIUrl":"10.1016/j.cct.2025.108210","url":null,"abstract":"<div><div>Background: Adults with multiple chronic conditions (MCC, defined as two plus chronic conditions) account for one-third of the United States population but 71 % of healthcare expenditures. Many adults with MCC also manage social needs like food insecurity or housing instability, which are associated with worse disease outcomes and decreased life expectancy. Research on social needs interventions demonstrated that targeted interventions can significantly improve care utilization and patient well-being. However, many published trials evaluating social needs navigation or resource referrals have focused on a single social need, specific health conditions, or a single intervention strategy.</div><div>Methods: This trial (“Addressing Social Needs to Improve Health in Adults with Multiple Chronic Conditions”) is a comparative-effectiveness randomized control trial (CE-RCT) comparing the clinical impact of two commonly implemented social needs interventions (“higher intensity” social needs phone navigation versus “lower intensity” automated electronic resource outreach). It will enroll 12,000 adults with MCC, one or more evidence-based clinical care gaps, and one or more social needs within Kaiser Permanente, an integrated delivery system serving over 12.5 million members. Participants can be randomized to a higher or lower intensity intervention. The primary outcomes are 12-month clinical care gap closures measured via electronic health records, and 6-month receipt of social services and reductions in social needs, measured via patient surveys. Secondary outcomes include survey and interview assessments of stress and experiences of social care.</div><div>Conclusion: Results from this CE-RCT provide policy and practice-relevant evidence comparing the impacts of different approaches to addressing social needs in patients with MCC.</div><div>Trial registration: <span><span>clinicaltrials.gov/study/NCT06941519</span><svg><path></path></svg></span></div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"161 ","pages":"Article 108210"},"PeriodicalIF":1.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843569","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 : 2026-02-01Epub Date: 2025-12-18DOI: 10.1016/j.cct.2025.108192
Andrea B. Goldschmidt , Adrian Ortega , Isabel R. Rooper , Katrina T. Obleada , Danielle A.N. Chapa , Basia Silverberg , Erin Stalvey , Macarena Kruger Camino , Michele D. Levine , Lan Yu , Dawn M. Eichen , Andrea K. Graham
Background
Pediatric overweight and obesity continue to be major public health issues. Loss of control (LOC) eating and overeating are two obesity-related phenotypes affecting approximately 30 % of adolescents with overweight/obesity that may undermine weight control treatment outcome. Cognitive-behavioral therapy (CBT) has promising effects on dysregulated eating, but effects on weight are modest, access is limited, and developmental changes in self-regulation (which may limit implementation of treatment skills) are often ignored. Methods: In the current proposal, we will apply human-centered design methods to design and test a novel CBT-based digital intervention, augmented with content and features to improve self-regulation, for weight gain prevention and dysregulated eating in adolescents. The first phase will involve design activities with adolescents (n = 25–30) who have body mass index (BMI; kg/m2) ≥ 75th percentile for age and sex and report dysregulated eating, to understand desired presentation, features, and barriers/facilitators to engagement. Research activities will include a needs assessment and iterative prototyping, usability testing, and refinement of the digital intervention. The second phase will be a multisite single arm open trial involving 50 adolescents who have or are at risk for overweight/obesity and report LOC and/or overeating to investigate intervention feasibility and preliminary efficacy, as well as putative treatment mechanisms and targets. Conclusions: Results of the study will inform the design of an adequately powered randomized controlled trial. The project has clear potential to significantly impact public health via development of a relevant, accessible, and scalable intervention for adolescents at risk for adverse physical and mental health outcomes.
{"title":"Virtual Intervention for Binge Eating (VIBE): Study protocol for a user-informed mobile intervention for dysregulated eating and weight gain prevention in adolescents","authors":"Andrea B. Goldschmidt , Adrian Ortega , Isabel R. Rooper , Katrina T. Obleada , Danielle A.N. Chapa , Basia Silverberg , Erin Stalvey , Macarena Kruger Camino , Michele D. Levine , Lan Yu , Dawn M. Eichen , Andrea K. Graham","doi":"10.1016/j.cct.2025.108192","DOIUrl":"10.1016/j.cct.2025.108192","url":null,"abstract":"<div><h3>Background</h3><div>Pediatric overweight and obesity continue to be major public health issues. Loss of control (LOC) eating and overeating are two obesity-related phenotypes affecting approximately 30 % of adolescents with overweight/obesity that may undermine weight control treatment outcome. Cognitive-behavioral therapy (CBT) has promising effects on dysregulated eating, but effects on weight are modest, access is limited, and developmental changes in self-regulation (which may limit implementation of treatment skills) are often ignored. <u>Methods</u>: In the current proposal, we will apply human-centered design methods to design and test a novel CBT-based digital intervention, augmented with content and features to improve self-regulation, for weight gain prevention and dysregulated eating in adolescents. The first phase will involve design activities with adolescents (<em>n</em> = 25–30) who have body mass index (BMI; kg/m<sup>2</sup>) ≥ 75th percentile for age and sex and report dysregulated eating, to understand desired presentation, features, and barriers/facilitators to engagement. Research activities will include a needs assessment and iterative prototyping, usability testing, and refinement of the digital intervention. The second phase will be a multisite single arm open trial involving 50 adolescents who have or are at risk for overweight/obesity and report LOC and/or overeating to investigate intervention feasibility and preliminary efficacy, as well as putative treatment mechanisms and targets. <u>Conclusions</u>: Results of the study will inform the design of an adequately powered randomized controlled trial. The project has clear potential to significantly impact public health via development of a relevant, accessible, and scalable intervention for adolescents at risk for adverse physical and mental health outcomes.</div><div><strong>Clinical trial registration number</strong>: <span><span>NCT06819813</span><svg><path></path></svg></span></div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"161 ","pages":"Article 108192"},"PeriodicalIF":1.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145789069","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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