Contemporary clinical trials最新文献

{"title":"Power considerations for the win ratio: A rank-based simulation approach","authors":"Lauren B. Bonner ,&nbsp;Jody D. Ciolino ,&nbsp;Keith S. Kaye ,&nbsp;Richard G. Wunderink ,&nbsp;Denise M. Scholtens","doi":"10.1016/j.cct.2025.107937","DOIUrl":"10.1016/j.cct.2025.107937","url":null,"abstract":"<div><h3>Background</h3><div>The win ratio is an innovative statistical method for evaluating efficacy in clinical trials. The underlying distributions of outcomes, along with potential censoring, ties, and correlations, add complexity to specifying a win ratio for study design purposes. As successful study planning hinges on thorough consideration of sample size and statistical power, we developed a flexible approach to support the use of the win ratio in clinical trials.</div></div><div><h3>Methods</h3><div>We develop a simulation-based approach for study design considerations, relying on the relationship between the win ratio and the rank distribution. We demonstrate that, in the absence of censoring and ties, the strategy samples according to the win ratio specified under the alternative hypothesis. We incorporate administrative censoring, ties, and correlations and conduct a simulation study to evaluate the method in terms of type I error and power. We generate data under specific parametric distributional assumptions and summarize statistical power using sample sizes determined by the rank-based simulation.</div></div><div><h3>Results</h3><div>Results indicate the proposed approach preserves type I error, samples under the assumed win ratio, and provides informative guidance on statistical power for given sample size. The winratiopss R package provides functionality to implement the proposed approach.</div></div><div><h3>Conclusions</h3><div>The simulation strategy offers a novel and flexible approach to inform trial design involving win ratio analysis.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"154 ","pages":"Article 107937"},"PeriodicalIF":2.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929500","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":"Brain-targeted goal-directed therapy in high-risk patients undergoing major elective surgery: Study protocol for the BRAIN-PROMISE randomized trial","authors":"Massimiliano Greco ,&nbsp;Giulio Calgaro ,&nbsp;Mattia Cavallo ,&nbsp;Sara Pugliese ,&nbsp;Marta Mascari ,&nbsp;Fabio Piccirillo ,&nbsp;Andrea Pradella ,&nbsp;Federico Piccioni ,&nbsp;Maurizio Cecconi","doi":"10.1016/j.cct.2025.107940","DOIUrl":"10.1016/j.cct.2025.107940","url":null,"abstract":"<div><h3>Background</h3><div>Perioperative complications can lead to increased morbidity and mortality, diminished patient's quality of life, and substantial economic burden. Elderly and frail patients are particularly vulnerable, facing higher risks of postoperative cognitive dysfunction and delirium.</div><div>Perioperative choices and anaesthesia management, including hemodynamic monitoring, anaesthesia depth, and fluid therapy can significantly impact long-term outcomes. Near-infrared spectroscopy (NIRS) is a technique for measuring regional oxygen saturation of brain tissue (rSO2) during surgery. Monitoring cerebral perfusion through rSO2 could estimate perfusion changes, identify early tissue hypoxia, and mitigate postoperative complications. Nonetheless, there is a lack of studies exploring NIRS-based hemodynamic optimization protocols in high-risk surgical populations.</div></div><div><h3>Object</h3><div>This prospective randomized controlled trial has been designed to evaluate whether NIRS-targeted goal-directed therapy can reduce rSO2 drop episodes and improve outcomes in high-risk elderly patients undergoing major surgery.</div></div><div><h3>Methods</h3><div>This randomized controlled trial will enroll hypertensive elderly patients aged ≥65 or with a clinical frailty score ≥ 5, undergoing moderate to high-risk surgery under general anaesthesia. Participants will be randomized 1:1 to either NIRS-targeted management or standard care, with NIRS monitoring applied to both groups but only guiding intervention in the experimental group, and with anesthesiologist blinded to NIRS value in control group. Primary outcomes include the overall incidence of perioperative complications at 30 days, secondary outcomes assess cognitive dysfunction, delirium, length of stay and mortality at 90 days.</div></div><div><h3>Conclusions</h3><div>This study presents an innovative approach on the effectiveness of NIRS-targeted goal directed for improving perioperative outcomes in high-risk elderly patients undergoing general anaesthesia.</div><div>Trial registration: <span><span>clinicaltrials.gov</span><svg><path></path></svg></span> registration, n. <span><span>NCT04266574</span><svg><path></path></svg></span>,</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"154 ","pages":"Article 107940"},"PeriodicalIF":2.0,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912586","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":"Assessing the role of correlation between efficacy and toxicity endpoints in the performance of Bayesian optimal phase II design","authors":"Xun Xu ,&nbsp;Ying Yuan ,&nbsp;J. Jack Lee","doi":"10.1016/j.cct.2025.107939","DOIUrl":"10.1016/j.cct.2025.107939","url":null,"abstract":"<div><div>Bayesian optimal phase II (BOP2) design serves to screen the efficacy and/or toxicity of a new treatment, determining whether it warrants further development. When employing the BOP2 design to jointly monitor the efficacy-toxicity tradeoff, the correlation between them plays an important role in achieving good performance on the statistical power while controlling Type I error. However, in practice, this correlation is usually unknown, posing challenges in the trial design and data analysis. In this study, the phi coefficient is chosen to measure the correlation. The influence of the efficacy-toxicity tradeoff on the power of BOP2 designs is first evaluated in the design stage and the data analysis stage, separately, then, overall considerations are given. In the design stage, we observe that the power increases as phi increases. Upon performing the sensitivity analysis in the data analysis stage, we find that the power decreases as phi increases given the pre-determined stopping boundaries. Simulations demonstrate instances of overpowering with inflated Type I error when the assumed phi in the design stage exceeds the true phi in the data analysis stage. Conversely, underpowering occurs with controlled Type I error when the assumed phi is lower than the true phi in the data analysis stage. To obtain the power under controlled Type I error in design, we recommend the use of independent correlation when the efficacy and toxicity are likely to be positively correlated. Conversely, for cases of likely negative correlation, taking a phi value close to the lower bound is advisable.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"154 ","pages":"Article 107939"},"PeriodicalIF":2.0,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935760","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":"Promoting mental health treatment initiation of veterans with PTSD using internet-based family training and telephone coaching: Protocol for a randomized controlled trial","authors":"Eric Kuhn ,&nbsp;Steven Sayers ,&nbsp;Lindsey Zimmerman ,&nbsp;Margaret-Anne Mackintosh ,&nbsp;Jason E. Owen ,&nbsp;Craig S. Rosen ,&nbsp;Laura A. Meis ,&nbsp;Hildi J. Hagedorn ,&nbsp;Christopher R. Erbes","doi":"10.1016/j.cct.2025.107929","DOIUrl":"10.1016/j.cct.2025.107929","url":null,"abstract":"<div><h3>Background</h3><div>Many veterans with posttraumatic stress disorder (PTSD) do not seek mental health care. Their significant others, including spouses and intimate partners, could be helpful in encouraging them to enter treatment. Community reinforcement and family training (CRAFT) has been shown to increase uptake in care among treatment-resistant individuals with alcohol and substance use disorders. We have adapted CRAFT for family members of veterans with PTSD and self-guided web-delivery with telephone coaching. A pilot study of this program showed promising results.</div></div><div><h3>Methods</h3><div>This paper describes a randomized controlled trial of the Veterans Affairs-CRAFT (VA-CRAFT) web program coupled with four telephone coaching calls from VA's Coaching Into Care (CIC) program compared to CIC as usual. Assessments will occur at baseline, posttreatment (3-mos.), and follow-up (6-mos.). Spouses and intimate partners of veterans with perceived, untreated PTSD (<em>N</em> = 230) will be randomized (1:1) to study conditions. We hypothesize that compared to CIC as usual, CIC + VA-CRAFT will result in more veterans initiating mental health care (Aim 1) without compromising CIC's existing high client satisfaction (Aim 2). We also will explore if participants show improved benefits in wellbeing in CIC + VA-CRAFT relative to CIC as usual (Exploratory Aim 1). Lastly, we will explore potential mediators and moderators of intervention effects (Exploratory Aim 2).</div></div><div><h3>Conclusion</h3><div>We expect results of this innovative trial will provide efficacy evidence for VA-CRAFT plus telephone coaching. If successful, findings can help support implementation efforts of VA-CRAFT into family services for veterans with PTSD who are reluctant to seek care.</div><div>Clinical Trial Registration Number: <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> <span><span>NCT04501328</span><svg><path></path></svg></span></div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"154 ","pages":"Article 107929"},"PeriodicalIF":2.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955687","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":"Bivalirudin infusion at standard or low regimen during elective percutaneous coronary intervention in high-risk bleeding patients with acute coronary syndrome: Study protocol for a prospective, single-center, randomized controlled trial","authors":"Yue Li ,&nbsp;Junxian Qi ,&nbsp;Yinghui Gong ,&nbsp;Tienan Zhou ,&nbsp;Lei Zhang ,&nbsp;Jing Li ,&nbsp;Xiaozeng Wang","doi":"10.1016/j.cct.2025.107941","DOIUrl":"10.1016/j.cct.2025.107941","url":null,"abstract":"<div><h3>Background</h3><div>Bleeding complications associated with anticoagulant therapy should receive more attention in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI), especially in those considered at high-risk bleeding. The recommended dosage of bivalirudin in clinical guidelines may not be appropriate for East Asian populations. We are performing a trial to investigate the efficacy and safety of a low bivalirudin regimen without prolonging infusion in high-risk bleeding patients with ACS undergoing elective PCI.</div></div><div><h3>Methods</h3><div>The study is a prospective, open-label, randomized controlled, non-inferiority trial. A total of 2510 patients will be enrolled and randomly (1,1) allocated to either receive the low (80 % of the standard dose) or standard bivalirudin regimen without prolonging the infusion after PCI. The primary endpoint is net adverse clinical events (NACE) at 30 days, which is a composite of major adverse cardiovascular and cerebrovascular events (MACCE, including all-cause death, repeat revascularization, stroke, nonfatal myocardial infarction, and stent thrombosis) and any bleeding events defined by the Bleeding Academic Research Consortium (BARC).</div></div><div><h3>Conclusions</h3><div>This proposed study is the first randomized controlled trial to evaluate the efficacy and safety of a low versus standard bivalirudin regimen during elective PCI in high-risk bleeding patients with ACS. The results may help achieve dose optimization for the use of perioperative bivalirudin in high-risk bleeding ACS patients undergoing elective PCI.</div></div><div><h3>Trial registration</h3><div>Chinese Clinical Trial Registry ChiCTR2200064363. Registered on October 4, 2022.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"154 ","pages":"Article 107941"},"PeriodicalIF":2.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912572","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":"Effect of cyclic daytime versus continuous enteral nutrition on circadian rhythms in critical illness (CIRCLES): Study protocol for a randomized controlled trial","authors":"Floor W. Hiemstra ,&nbsp;Marit F. van Gent ,&nbsp;Evert de Jonge ,&nbsp;David J. van Westerloo ,&nbsp;Laura Kervezee","doi":"10.1016/j.cct.2025.107927","DOIUrl":"10.1016/j.cct.2025.107927","url":null,"abstract":"<div><h3>Background</h3><div>Circadian rhythms and sleep are often disrupted in critically ill patients in the intensive care unit (ICU), which has been linked to poor clinical outcomes. Feeding-fasting cycles serve as a synchronizing cue for the circadian timing system, indicating that optimizing these cycles in the ICU could reinforce circadian rhythms. The CIRCLES trial evaluates whether cyclic daytime enteral nutrition improves 24-h rhythms in critically ill patients compared to continuous enteral nutrition.</div></div><div><h3>Objective</h3><div>To describe the study protocol for the CIRCLES study.</div></div><div><h3>Study design</h3><div>The CIRCLES study is an investigator-initiated randomized controlled trial in a tertiary care ICU in the Netherlands. Patients (aged ≥18 years) admitted to the ICU with an expected stay ≥48 h receiving or with intention to start enteral nutrition are eligible for inclusion. Patients (<em>n</em> = 60) are randomized to the <em>continuous</em> enteral nutrition (nutrition around the clock) or <em>cyclic</em> daytime enteral nutrition group (nutrition between 08:00 h to 20:00 h).</div></div><div><h3>Main outcome measures</h3><div>The primary outcome is the amplitude of 24-h rhythms in core body temperature. Secondary outcomes include 24-h rhythms in heart rate, mean blood pressure heart rate variability, melatonin and gene expression, glucose regulation, insulin administration, caloric intake and feeding intolerance.</div></div><div><h3>Conclusion</h3><div>We hypothesize that a cyclic daytime feeding strategy will result in a higher amplitude of 24-h rhythms in vital signs, heart rate variability, and melatonin, compared to continuous feeding, thereby suggesting improved circadian rhythm strength. This study aims to provide insight into strategies to optimize circadian rhythms in ICU patients.</div></div><div><h3>Trial registration</h3><div>Registered at <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (<span><span>NCT05795881</span><svg><path></path></svg></span>), April 2023.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"154 ","pages":"Article 107927"},"PeriodicalIF":2.0,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899630","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":"Workforce and systems change to treat adolescent substance use disorder within integrated pediatric primary care: A cluster-randomized stepped-wedge trial","authors":"Leslie A. Hulvershorn ,&nbsp;Matthew Aalsma ,&nbsp;Trey V. Dellucci ,&nbsp;Ashlyn Burns ,&nbsp;Brigid R. Marriott ,&nbsp;Bernice Pescosolido ,&nbsp;Harold D. Green Jr. ,&nbsp;Lisa Saldana ,&nbsp;Jason Chapman ,&nbsp;Patrick Monahan ,&nbsp;Sarah E. Wiehe ,&nbsp;Edward J. Miech ,&nbsp;Zachary W. Adams","doi":"10.1016/j.cct.2025.107928","DOIUrl":"10.1016/j.cct.2025.107928","url":null,"abstract":"<div><h3>Background</h3><div>While the overdose crisis has impacted all ages, overdose-related deaths among adolescents have been increasing more rapidly than any other age group, doubling between 2019 and 2020. Identifying and treating substance use disorders (SUDs) among adolescents is critical to preventing adolescent overdose deaths. While evidence-based interventions for adolescents with SUDs exist, they remain underutilized. Implementing SUD interventions in primary care settings through integrated behavioral health (IBH) is one approach for increasing access to evidence-based SUD services for adolescents.</div></div><div><h3>Methods</h3><div>This is a Hybrid Type 2, cluster-randomized, stepped-wedge trial comparing SUD IBH to standard primary care treatment. In our open cohort stepped-wedge design, primary care clinics will be randomly designated to one of three cohorts. We will use a mixed-methods approach to evaluate both implementation and effectiveness outcomes, with a focus on assessing the impact of IBH on primary care provider behaviors around SUD interventions. All cohorts will complete baseline surveys during the control condition and then every 6 months. At each time point, we will also collect and analyze patient administrative data to assess patient engagement and outcomes. In addition, we will conduct qualitative interviews at pre-, mid-, and post-implementation during sustainment of the intervention.</div></div><div><h3>Conclusion</h3><div>Addressing the overdose crisis is a national priority. IBH has the potential to reduce overdose rates by enhancing primary care provider willingness to deliver SUD services for adolescents.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"154 ","pages":"Article 107928"},"PeriodicalIF":2.0,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892153","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 data credibility in online recruitment: Signs and strategies for detecting fraudulent participants when using ResearchMatch","authors":"Lauren M. Pageau,&nbsp;Jiying Ling","doi":"10.1016/j.cct.2025.107925","DOIUrl":"10.1016/j.cct.2025.107925","url":null,"abstract":"<div><h3>Introduction</h3><div>Online recruitment platforms are valuable tools that allow researchers to efficiently reach large pools of potential participants for clinical trials and observational studies. However, challenges associated with fraudulent respondents and bots threaten data credibility. This paper discusses signs we identified for recognizing potentially fraudulent respondents when using one online recruitment tool, ResearchMatch, to recruit study participants.</div></div><div><h3>Methods</h3><div>Participants were recruited via ResearchMatch for a study focused on stress and coping among U.S. young, low-income parents. Participants completed an online survey via Qualtrics. To screen for fraudulent respondents, we compared reports generated from Qualtrics with those from ResearchMatch.</div></div><div><h3>Results</h3><div>We identified six signs of fraudulent respondents, including 1) suspicious metadata, 2) fake addresses listed in ResearchMatch profile, 3) a common Western name for both first and last names, 4) inconsistent and duplicate data, 5) extensive list of medications and/or medical conditions, and 6) short survey completion time. We contacted 63,284 accounts through ResearchMatch and received 928 survey responses. About 46 % (<em>n</em> = 425) of responses were deemed fraudulent.</div></div><div><h3>Conclusions</h3><div>Fraudulent respondents and bots undermine the integrity of data, which may result in adverse implications for research, policy, and patient health. Given that nearly half of the survey respondents in our study were deemed fraudulent, it is evident that this is a significant issue for recruiting research participants via online recruitment platforms. To ensure reliability and accuracy of study findings, it is critical for researchers to thoroughly examine their data for signs of fraudulence.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"154 ","pages":"Article 107925"},"PeriodicalIF":2.0,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886426","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":"Rationale and design of a randomized controlled trial evaluating the effects of blueberry consumption versus placebo on brain health in older adults","authors":"Zachary Uttke ,&nbsp;Olivia Gabriel ,&nbsp;Ceilidh Smith ,&nbsp;Eric T. Guardino ,&nbsp;Kenneth Mukamal ,&nbsp;Luc Djousse","doi":"10.1016/j.cct.2025.107926","DOIUrl":"10.1016/j.cct.2025.107926","url":null,"abstract":"<div><h3>Background</h3><div>Age-related cognitive decline results in significant clinical and public health costs. Cognitive decline predisposes individuals to dementia and leads to difficulties with activities of daily living and increased hospitalizations. While a few dietary interventions have shown considerable promise at delaying cognitive decline, studies of the effects of long-term blueberry consumption on brain health among older adults have been limited and equivocal.</div></div><div><h3>Objective</h3><div>To test the hypothesis that a 24-week intervention with blueberry powder versus placebo will improve (i) plasma biomarkers of brain health and (ii) cognitive performance in older adults.</div></div><div><h3>Methods</h3><div>This randomized, double-blind, placebo-controlled trial will be conducted in older Americans aged 65–99 years old. Sixty-seven participants will be randomly assigned to receive either blueberry powder (20 g/d – equivalent of one (1) cup of fresh blueberries) or a placebo powder (20 g/d) for 24 weeks. Participants will undergo four clinic visits (baseline and 8 weeks, 16 weeks, and 24 weeks after randomization) for cognitive assessments, blood pressure measurements, and blood sample collections. Primary outcomes will be plasma levels of neurofilament light chain (NFL) and phosphorylated tau protein (pTau-181). Secondary outcomes will be plasma levels of glial fibrillary acidic protein (GFAP) and non-esterified fatty acids (NEFA); blood pressure during visits; and cognitive function.</div></div><div><h3>Conclusion</h3><div>Findings from this trial will answer the question whether a long-term intervention with blueberry powder can improve (i) plasma biomarkers of brain health and (ii) cognitive function in older adults.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"154 ","pages":"Article 107926"},"PeriodicalIF":2.0,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903962","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 randomized, placebo-controlled, double-masked mechanistic clinical trial of transdermal estrogen replacement in hypoestrogenic eating disorders to explore the role of estrogen on cognitive flexibility and reward processing","authors":"Lauren Breithaupt ,&nbsp;Meghan Slattery ,&nbsp;Meghan Lauze ,&nbsp;Felicia Petterway ,&nbsp;Lauren Lindman ,&nbsp;Mia Cravitz ,&nbsp;Sarah Naticchia ,&nbsp;Siddarth Seenivasa ,&nbsp;Macy Powers ,&nbsp;Kristin N. Javaras ,&nbsp;David J. Alperovitz ,&nbsp;Judith Halperin ,&nbsp;Esther Dechant ,&nbsp;Jennifer J. Thomas ,&nbsp;Elizabeth A. Lawson ,&nbsp;Hang Lee ,&nbsp;Diego A. Pizzagalli ,&nbsp;Adrienne L. Romer ,&nbsp;Poornima Kumar ,&nbsp;Franziska Plessow ,&nbsp;Kamryn T. Eddy","doi":"10.1016/j.cct.2025.107924","DOIUrl":"10.1016/j.cct.2025.107924","url":null,"abstract":"<div><h3>Background</h3><div>Restrictive eating disorders (EDs) are associated with cognitive inflexibility, reduced reward responsiveness, and tendency to favor delayed rewards, which contribute to illness maintenance and poor outcomes. Low estrogen is common in EDs and has been linked to poor cognitive flexibility and reward processing in other conditions. We describe a randomized controlled double-masked trial of short-term (12 weeks) transdermal estrogen (100 μg 17-β) replacement versus placebo to test estrogen-effects on cognitive flexibility, reward responsiveness, delay discounting, and ED pathology in females with EDs and low estrogen (ED-LE).</div></div><div><h3>Methods</h3><div>Participants will include <em>N</em> = 120 females with ED-LE (14–35 years) with clinical, neuropsychological, and neural assessments occurring at baseline, eight weeks, and 12 weeks.</div></div><div><h3>Results</h3><div>Primary outcomes will include between-group differences in 8-week change in cognitive flexibility, reward responsiveness, and delay discounting, and between-group differences in 12-week change in ED pathology. Secondary outcomes will include between-group differences in 8-week change in neural activation during cognitive flexibility and reward-related functional magnetic resonance imaging paradigms and mediation effects of 8-week change in cognitive flexibility, reward responsiveness, and delay discounting on 12-week change in ED pathology.</div></div><div><h3>Conclusion</h3><div>We hypothesize that estrogen replacement will (1) increase cognitive flexibility, reward responsiveness, and delay discounting, and (2) reduce ED pathology; and (3) 8-week changes in cognitive flexibility, reward responsiveness, and delay discounting will mediate 12-week changes in ED pathology. These data will systematically probe the role of estrogen in key neurocognitive features associated with poor ED outcomes to guide development of novel interventions for this population.</div></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":"154 ","pages":"Article 107924"},"PeriodicalIF":2.0,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916394","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}