Contemporary clinical trials最新文献

{"title":"Structural innovation for hypoglycemia prevention in high-risk patients with type 2 diabetes: Design and implementation of a pragmatic, randomized, quality improvement trial","authors":"Minnie W. Chen ,&nbsp;Melissa M. Parker ,&nbsp;Andrew J. Karter ,&nbsp;Richard W. Grant ,&nbsp;Lisa K. Gilliam","doi":"10.1016/j.cct.2025.107885","DOIUrl":"10.1016/j.cct.2025.107885","url":null,"abstract":"<div><div>Severe hypoglycemia is a potentially life-threatening complication of diabetes treatment, associated with increased risks of falls, cardiovascular events, cognitive decline, and mortality. This critical public health concern remains inadequately recognized and addressed in many clinical settings. Here we describe the development of a clinical guideline and associated protocol for a quality improvement randomized trial for hypoglycemia prevention, embedded within an integrated healthcare system. First, we engaged expert clinical stakeholders and experienced guideline developers to create an evidence-based hypoglycemia prevention algorithm, “<strong>Hypoglycemia on a Page” (HOAP</strong>), which was published internally as a healthcare system guideline. After system-wide, passive dissemination of HOAP, a pragmatic, quality improvement, randomized trial was implemented to study the benefit of a proactive, HOAP protocol-driven outreach by a clinical pharmacist targeting hypoglycemia-prone patients with T2D (Intervention Arm) compared to usual care (Usual Care Arm). As the primary outcome, we will assess whether patients in the Intervention Arm are prescribed safer (less hypoglycemia-prone) diabetes regimens compared to the Usual Care Arm. We hypothesize that the proactive, protocol-driven outreach will result in safer diabetes regimens compared to HOAP dissemination alone. Secondary outcomes of interest include prescribing of glucagon (for rapid treatment of severe hypoglycemia episodes), prescribing and dispensing of continuous glucose monitoring (CGM), documenting hypoglycemia on the problem list, glycemic control (HbA1c &lt;8 %), and ED visit or hospital admission for hypoglycemia. This pragmatic clinical trial will evaluate a structural innovation that included care strategies designed to reduce harm, improve patient outcomes and reduce healthcare resource utilization and cost.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"152 ","pages":"Article 107885"},"PeriodicalIF":2.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662922","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}

{"title":"Pirfenidone to prevent fibrosis in acute respiratory distress syndrome: The PIONEER study protocol.","authors":"Giacomo Monti, Matteo Marzaroli, Maria Teresa Tucciariello, Brian Ferrara, Francesco Meroi, Cristina Nakhnoukh, Massimo Zambon, Giovanni Borghi, Fabio Guarracino, Marco Manazza, Valentina Ajello, Alessandro Belletti, Cesare Biuzzi, Valentina Plumari, Matteo Filippini, Raffaele Cuffaro, Gabriele Racanelli, Domenico Pontillo, Simon Rauch, Federico Mattia Oliva, Marco Tescione, Martina Baiardo Redaelli, Gabriele Melegari, Giulia Maj, Paolo Navalesi, Michele Gerardi, Alessio Caccioppola, Andrea Bruni, Andrea Ballotta, Camilla Ferri, Daniele Orso, Vincenzo Di Benedetto, Rubia Baldassarri, Giulia Franceschini, Ans Alamami, Laura Pasin, Alessandro Putzu, Carolina Soledad Romero Garcia, Yih-Sharng Chen, Alberto Noto, Andrey Yavorovskiy, Ludhmila Abrahao Hajjar, Andrea Cortegiani, Valery Likhvantsev, Aidos Konkayev, Gabriele Finco, Gabriele Sales, Luca Brazzi, Gianluca Paternoster, Rinaldo Bellomo, Alberto Zangrillo, Giovanni Landoni, Nora Di Tomasso","doi":"10.1016/j.cct.2025.107883","DOIUrl":"https://doi.org/10.1016/j.cct.2025.107883","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary fibrosis is a major complication of the Acute Respiratory Distress Syndrome (ARDS). Pirfenidone is an approved treatment for idiopathic pulmonary fibrosis. It may attenuate ARDS-related fibrosis and decrease the need for prolonged ventilation. Accordingly, we aimed to evaluate the effect of pirfenidone on ventilator-free days in patients with ARDS.</p><p><strong>Methods: </strong>In a multi-center, randomized, double-blind, placebo-controlled trial, we plan to randomly assign 130 adults invasively ventilated for ARDS to receive pirfenidone or placebo for up to 28 days. The primary outcome is days alive and ventilator free at 28 days. Secondary outcomes include ICU-free days, hospital free days all at 28 day, ICU mortality and hospital mortality. We will also assess fibroproliferative changes on high-resolution CT scans at ICU discharge and quality of life. Data analysis will be on an intention-to-treat basis.</p><p><strong>Discussion: </strong>The trial is ongoing and currently recruiting. It will be the first randomized controlled study to investigate whether, compared to placebo, pirfenidone reduces the number of days alive and ventilator-free in patients with ARDS. Its double-blind multicenter design will provide internal validity, minimal bias, and a degree of external validity. If our hypothesis is confirmed, this treatment would justify larger trials of this intervention.</p><p><strong>Trial registration: </strong>This trial was registered on ClinicalTrials.gov with the trial identification NCT05075161.</p>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":" ","pages":"107883"},"PeriodicalIF":2.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639481","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}

{"title":"Improving maternal postpartum access to care through telemedicine (IMPACT): A multi-center randomized controlled trial of postpartum interventions to improve access and outcomes","authors":"Ran Zhang ,&nbsp;Sheree L. Boulet ,&nbsp;David B. Nelson ,&nbsp;Peggy Goedken ,&nbsp;Jacqueline Catchings ,&nbsp;Donald McIntire ,&nbsp;Marissa Platner ,&nbsp;Robert B. Martin ,&nbsp;Catherine Y. Spong ,&nbsp;Elaine L. Duryea","doi":"10.1016/j.cct.2025.107882","DOIUrl":"10.1016/j.cct.2025.107882","url":null,"abstract":"<div><h3>Background</h3><div>Postpartum care is essential for maternal health and significantly impacts long-term health outcomes, yet it remains inadequately addressed, particularly among Non-Hispanic Black and Hispanic individuals. The primary objective of the Improving Maternal Postpartum Access to Care through Telemedicine (IMPACT) study is to compare the effectiveness of two postpartum care models on early postpartum complication detection, hospital readmission prevention, postpartum health knowledge, quality of life, and chronic medical condition management among medically underserved individuals.</div></div><div><h3>Method</h3><div>The IMPACT study is a multi-center, randomized controlled trial conducted at Parkland Hospital in Dallas, Texas, and Grady Memorial Hospital in Atlanta, Georgia. It aims to compare two postpartum care models (intensive education vs. enhanced virtual care) among 3500 Non-Hispanic Black and Hispanic postpartum individuals of lower socioeconomic status. Phase I (year 1) involves collecting baseline data and refining the study based on patient feedback. Phase II (year 2–4) continues recruiting participants and assigns them to each model randomly. Data collection spans a one-year follow-up period (1 week, 6 weeks, 3 months, 6 months, and 1 year after enrollment), including maternal health outcomes, mental health assessments, laboratory tests, and patient-reported measures.</div></div><div><h3>Conclusion</h3><div>The IMPACT study provides an innovative approach to postpartum care, utilizing telemedicine to enhance access and education for underserved populations. The study findings will have significant implications for healthcare providers and policymakers, offering evidence-based guidance for optimizing postpartum care delivery and informing clinical guidelines that can help reduce maternal health disparities.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"152 ","pages":"Article 107882"},"PeriodicalIF":2.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639477","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}

{"title":"Comprehensive geriatric assessment for frail older people with chronic kidney disease to increase attainment of patient-identified goals: Statistical analysis plan for a cluster-randomised controlled trial","authors":"Gabor Mihala ,&nbsp;Ruth Eleanor Hubbard ,&nbsp;Benignus Logan ,&nbsp;David Wayne Johnson ,&nbsp;Andrea Katharina Viecelli ,&nbsp;Andrew Benjamin Forbes","doi":"10.1016/j.cct.2025.107881","DOIUrl":"10.1016/j.cct.2025.107881","url":null,"abstract":"<div><h3>Background</h3><div>Frailty is highly prevalent in older people with chronic kidney disease (CKD) and associated with more complex healthcare needs. As part of person-centred care, healthcare planning should be tailored to the individual's needs and their desired outcomes. Comprehensive Geriatric Assessment (CGA) is an intervention which can help facilitate this by identifying a person's medical, functional, and psychosocial problems, and then tailoring a coordinated, targeted management plan. The GOAL trial was designed to establish whether, compared to usual care, a CGA would better enable a person to achieve their own set goals, as measured by Goal Attainment Scaling (GAS). This paper presents the statistical analysis plan (SAP) for the GOAL trial.</div></div><div><h3>Methods</h3><div>The GOAL trial is a pragmatic, multi-centre, superiority, open-label, cluster-randomised controlled trial designed to enrol 500 frail, older people (Frailty Index &gt;0.25, aged ≥65 or ≥ 55 years if First Nations people) with moderate to severe CKD (estimated glomerular filtration rate &lt; 59 mL/min/1.73m²) across 16 hospital sites in Australia, and 12 months of follow-up. The primary question (effect of CGA on GAS at 3 months) will be modelled using mixed-effects linear regression. The SAP details the analysis and reporting methods.</div></div><div><h3>Conclusions</h3><div>The SAP described here resulted from an iterative, collaborative effort among statisticians and clinician leads of the GOAL trial. Specification of statistical methods prior to trial completion will contribute to unbiased analyses of the collected data.</div></div><div><h3>Trial registration</h3><div><span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> <span><span>NCT04538157</span><svg><path></path></svg></span></div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"152 ","pages":"Article 107881"},"PeriodicalIF":2.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Championing hypertension remote monitoring for equity and dissemination (CHARMED): A multi-site factorial randomized controlled trial protocol","authors":"Courtney R. Lyles ,&nbsp;Elaine C. Khoong ,&nbsp;Rachel J. Stern ,&nbsp;Nooshin Abtahi ,&nbsp;Anjana E. Sharma ,&nbsp;Mark J. Pletcher ,&nbsp;Fan Xia ,&nbsp;Faviola Garcia ,&nbsp;Nilpa D. Shah ,&nbsp;Lina Tieu ,&nbsp;Urmimala Sarkar ,&nbsp;the CHARMED consortium","doi":"10.1016/j.cct.2025.107879","DOIUrl":"10.1016/j.cct.2025.107879","url":null,"abstract":"<div><h3>Introduction</h3><div>We have evidence-based strategies such as remote patient monitoring and digital health tools to improve hypertension outcomes. Still, we lack large-scale studies focusing on disseminating these practices into routine clinical care. This is especially important to study within safety-net healthcare settings that disproportionately care for marginalized patient populations.</div></div><div><h3>Methods</h3><div>We will conduct a hybrid type 1 implementation trial (2 × 2 factorial design) with 25 safety-net clinics across three of California's public healthcare delivery systems, enrolling 2500 English- and Spanish-speaking patients with uncontrolled hypertension. Clinics will be randomized to receive baseline training on best practices in remote monitoring for hypertension management vs. training plus ongoing practice facilitation to support its implementation. Patients within these clinics will be randomized to receive cellular-enabled blood pressure monitors and automatic text message reminders to check their blood pressure at home vs. receipt of the same monitors as well as additional support via individually tailored text message feedback and support for hypertension management.</div></div><div><h3>Results</h3><div>The primary outcome will be a change in systolic blood pressure collected during routine office visits. Secondary outcomes include changes in home blood pressure and patient-reported assessments of clinical care and medication adherence. Given the hybrid type I trial implementation, the primary implementation outcomes will be the adoption of intervention at the patient and clinic levels.</div></div><div><h3>Discussion</h3><div>The evidence from this trial will advance implementation-focused research on hypertension management, such as the essential combination of both patient- and clinic-facing intervention strategies.</div></div><div><h3>Trial Registration</h3><div>NCT, <span><span>NCT06113458</span><svg><path></path></svg></span>. Registered 23 October 2023, <span><span>https://clinicaltrials.gov/study/NCT06113458</span><svg><path></path></svg></span></div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"152 ","pages":"Article 107879"},"PeriodicalIF":2.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630036","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}

{"title":"Handling non-ignorable missing intimal hyperplasia data – Lessons from the VEST trial","authors":"Jessica R. Overbey ,&nbsp;Samantha Raymond ,&nbsp;Helena Chang ,&nbsp;Emilia Bagiella","doi":"10.1016/j.cct.2025.107878","DOIUrl":"10.1016/j.cct.2025.107878","url":null,"abstract":"<div><div>Non-ignorable missing data arise often in clinical trials. The VEST trial, a randomized, within-patient-controlled study, assessed the effect of an external scaffold for saphenous vein grafts on intimal hyperplasia (IH) one year after coronary artery bypass graft surgery. It was anticipated that approximately 13 % of grafts would be occluded and unsuitable for intravascular ultrasound, resulting in missing IH values at 1-year. Given graft occlusion is a negative outcome and higher IH is associated with occlusion, this missing data is non-ignorable. To address this, we developed a novel two-part method for the MNAR (missing not at random) scenario in the VEST trial. This method combines penalized multiple imputation with a modified Wilcoxon signed-rank test. We evaluated the approach's performance against alternatives in a series of simulation studies. The new method did not show type I error inflation. Under trial assumptions, it provided adequate power. However, if missing data exceeds 20 %, power decreases notably with the double penalization method due to underestimation of the treatment effect. When missing data is balanced between arms, penalized multiple imputation alone is more powerful and unbiased. Conversely, for unbalanced MNAR data, as might occur with a treatment effect on IH, the penalized multiple imputation with a modified Wilcoxon signed-rank test approach is more powerful. The VEST trial showed more occlusions than expected, balanced across arms, resulting in potential underestimation of the true treatment effect. However, given the potential for unbalanced missingness, this approach was suitable and could be applied in other settings with similar challenges.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"152 ","pages":"Article 107878"},"PeriodicalIF":2.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627826","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}

{"title":"Corrigendum to “Reopening schools safely and educating youth (ROSSEY) study: Protocol for a community-based, cluster randomized controlled trial” [Contemporary Clinical Trials, 139 (2024) 107480]","authors":"Magaly Ramirez ,&nbsp;Parth D. Shah ,&nbsp;Helen Y. Chu ,&nbsp;Lorenzo Garza ,&nbsp;Sandra Linde ,&nbsp;Michelle M. Garrison ,&nbsp;Chuan Zhou ,&nbsp;Sonia Bishop ,&nbsp;Genoveva Ibarra ,&nbsp;Linda K. Ko","doi":"10.1016/j.cct.2025.107873","DOIUrl":"10.1016/j.cct.2025.107873","url":null,"abstract":"","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"152 ","pages":"Article 107873"},"PeriodicalIF":2.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623926","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}

{"title":"Study protocol for a duration-randomized clinical trial to determine the optimal length of treatment for multidrug-resistant tuberculosis with a 5-drug regimen: The DRAMATIC trial","authors":"Pawandeep Kaur ,&nbsp;Lelia H. Chaisson ,&nbsp;Zana Wangari Kiragu ,&nbsp;Praewpannarai Buddadhumaruk ,&nbsp;Ariana F. Austin ,&nbsp;Yilan Gao ,&nbsp;Veronika J. Wirtz ,&nbsp;Robert D. Arbeit ,&nbsp;Krystle Bliss Fetalvero ,&nbsp;Hoa Binh Nguyen ,&nbsp;Nhung Viet Nguyen ,&nbsp;Huy Ha ,&nbsp;Kathleen Eisenach ,&nbsp;Nicholas D. Walter ,&nbsp;Carole D. Mitnick ,&nbsp;Maria Tarcela S. Gler ,&nbsp;Ha Phan ,&nbsp;Payam Nahid ,&nbsp;Patrick P.J. Phillips ,&nbsp;C. Robert Horsburgh ,&nbsp;Gustavo E. Velásquez","doi":"10.1016/j.cct.2025.107875","DOIUrl":"10.1016/j.cct.2025.107875","url":null,"abstract":"<div><h3>Background</h3><div>Current guidelines for the treatment of multidrug-resistant/rifampin-resistant tuberculosis (MDR/RR-TB) are based on clinical trials evaluating fixed duration regimens. However, when a regimen succeeds, it remains unknown whether a shorter duration could yield the same results. Similarly, if a regimen fails, it is unclear whether extending the treatment could improve outcomes. Trials are needed to assess the relationship between various treatment durations and outcomes.</div></div><div><h3>Methods/design</h3><div>We designed a duration-randomized trial of treatment for fluoroquinolone-susceptible MDR/RR-TB. The DRAMATIC (<u>D</u>uration <u>R</u>andomized <u>A</u>nti-<u>M</u>DR-TB <u>A</u>nd <u>T</u>ailored <u>I</u>ntervention <u>C</u>linical) Trial is a multicenter, randomized, partially blinded, four-arm, phase 2 trial that examines an all oral, pyrazinamide-free regimen of bedaquiline, clofazimine, delamanid, linezolid, and levofloxacin, with administration of linezolid only in the initial 16 weeks of treatment. The four trial arms are treatment durations of 16, 24, 32 and 40 weeks. Randomization is stratified by “extensive” or “non-extensive” disease based on baseline smear (or Xpert) and cavitary status. The primary endpoint is relapse-free survival at week 76. The target sample size is 220. Participants are being enrolled in sites in the Philippines and Vietnam. The expected output will be an equation describing the relationship between treatment duration and the proportion of participants with relapse-free survival.</div></div><div><h3>Discussion</h3><div>This trial aims to demonstrate that a duration-response relationship can be described for the treatment of MDR/RR-TB by a duration-randomized trial.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"152 ","pages":"Article 107875"},"PeriodicalIF":2.0,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of virtual reality mindfulness on cognition and well-being in ALS: A randomized trial protocol","authors":"Juliette Faure-de Baets ,&nbsp;Jeremy Besnard ,&nbsp;Frédéric Banville ,&nbsp;Julien Cassereau ,&nbsp;Philippe Allain","doi":"10.1016/j.cct.2025.107876","DOIUrl":"10.1016/j.cct.2025.107876","url":null,"abstract":"<div><div>Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease primarily affecting motor neurons but also leading to significant non-motor symptoms, including cognitive impairments, anxiety, depression, and behavioral changes, which severely impact quality of life. While mindfulness-based interventions (MBIs) have shown promise in alleviating psychological distress, their accessibility is often limited due to patients' physical impairments. Virtual reality (VR) could enhance engagement and immersion, offering a novel, more inclusive therapeutic approach. This randomized controlled trial (RCT) aims to evaluate the efficacy of a VR-based MBI compared to traditional mindfulness for ALS patients. Forty-six participants will be randomly assigned to an eight-week mindfulness program delivered either via VR or in a conventional format. The primary outcome is quality of life, assessed using the ALS-Specific Quality of Life Scale (ALSSQOL-R). Secondary outcomes include cognitive function, anxiety, depression, behavioral changes, and mindfulness propensity, evaluated at baseline, post-intervention, and three-month follow-up. The study will also examine VR usability and potential accessibility challenges for ALS patients. By addressing a critical gap in non-pharmacological psychological care, this study will provide key insights into the feasibility and benefits of VR-based MBIs. If effective, VR mindfulness could offer an innovative, scalable solution to improve emotional well-being and quality of life in ALS, making psychological support more accessible for patients with severe physical limitations.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"152 ","pages":"Article 107876"},"PeriodicalIF":2.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563005","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}

{"title":"Development of a pharmacodynamic biomarker of opioid antagonism in adolescents with eating disorders: Study protocol for the naltrexone neuroimaging randomized controlled trial (NN-RCT)","authors":"Stephani L. Stancil ,&nbsp;Mariah E. Brewe ,&nbsp;John Tumberger ,&nbsp;Michael Bartkoski ,&nbsp;Anna Burns ,&nbsp;Hung-Wen Yeh ,&nbsp;Morgan G. Brucks ,&nbsp;James Bartolotti ,&nbsp;Michaela Voss ,&nbsp;Jeffrey R. Strawn ,&nbsp;Susan Abdel-Rahman ,&nbsp;Ann Davis ,&nbsp;William M. Brooks ,&nbsp;Laura E. Martin","doi":"10.1016/j.cct.2025.107874","DOIUrl":"10.1016/j.cct.2025.107874","url":null,"abstract":"<div><div>Eating disorders (ED) affect 5 % of youth, are associated with reward system alterations, and lead to substantial morbidity. Naltrexone, an opioid antagonist, is used to treat ED behaviors such as binge eating and purging. However, not all patients respond, and the optimal dose is unknown. Neuroimaging may serve as a tool to detect drug response in the brain, acting as a pharmacodynamic biomarker to support therapeutic optimization. Currently, no pharmacodynamic biomarkers for psychopharmacology exist. Building on pilot work, we present the protocol for a randomized controlled trial to validate neuroimaging as a pharmacodynamic biomarker of opioid antagonism in adolescents with ED. Youth aged 13–21 years with binge/purge ED are randomized to receive a single dose of oral naltrexone and placebo in a double-blind using a crossover design with an interdose interval ≥ 2 weeks. Task-based functional neuroimaging detects reward pathway modulation 2 h post-dose. Blood and urine are collected over a model-informed time course. Response (primary outcome) is defined as naltrexone-related blood oxygenation-level dependent signal change (Δ%BOLD) in a priori reward regions of interest and secondary exposure outcomes are naltrexone C_max and AUC_0-∞. Cohen's <em>d</em> will determine Δ%BOLD effect size, and an exposure-response model will identify target exposure to guide future dosing. This study addresses a critical knowledge gap by developing a non-invasive pharmacodynamic biomarker for youth with ED, with future applications in quantitative pharmacology, precision dosing, and the development of novel therapeutics.</div><div><span><span>NCT05509257</span><svg><path></path></svg></span></div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"152 ","pages":"Article 107874"},"PeriodicalIF":2.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565959","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}