Contemporary clinical trials最新文献

{"title":"The combination of donepezil and cognitive training for improving treatment outcomes for alcohol use disorder: Design of a randomized controlled trial","authors":"","doi":"10.1016/j.cct.2024.107657","DOIUrl":"10.1016/j.cct.2024.107657","url":null,"abstract":"<div><h3>Background</h3><p>The development of alcohol use disorder (AUD) is a major concern in public health, and cognitive impairments caused by alcohol are involved in this process. Emerging neurobiological evidence suggests that donepezil, an anticholinesterase agent, may improve AUD treatment outcomes by enhancing neurocognitive functioning. Previous research has also suggested that cognitive remediation therapy (CRT) could potentially improve cognitive function and AUD treatment outcomes. We present the rationale and design of a trial to evaluate the combination of donepezil and cognitive remediation therapy (donepezil + CRT) as an intervention for AUD.</p></div><div><h3>Methods</h3><p>We propose a 13-week, randomized, double-blind, placebo-controlled, between-subjects trial comparing 4 groups (donepezil + CRT vs. donepezil alone vs. CRT alone vs. placebos) as an intervention for AUD. The main goal of the study is to evaluate if donepezil + CRT is superior to placebo in reducing heavy drinking days and improving neurocognitive functioning. A total of 160 patients (4 groups, 40 per each group) with AUD between the ages of 18–80 years will be recruited at Yale University and the VA Connecticut Healthcare System. Primary outcome measures include 1) heavy drinking by Timeline Follow Back (TLFB) over 13 weeks and 2) global neurocognitive functioning by a global index of neurocognitive function score at 7 and 13 weeks.</p></div><div><h3>Discussion</h3><p>This protocol paper describes the rationale and proposed methods for the randomized controlled trial for improving AUD treatment outcomes. This project has significant clinical potential to help patients suffering from AUD by improving their cognition and reducing alcohol consumption.</p><p><em>Trial Registration:</em> <span><span>NCT05042102</span><svg><path></path></svg></span></p></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901173","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":"Protocol of a multisite randomized controlled trial of Bright IDEAS-Young Adults: Problem-solving skills training to reduce distress among young adults with Cancer","authors":"","doi":"10.1016/j.cct.2024.107656","DOIUrl":"10.1016/j.cct.2024.107656","url":null,"abstract":"<div><h3>Background</h3><p>Young adults with cancer diagnosed between the ages of 18 to 39 are recognized as a vulnerable group with unique emotional, social, and practical needs that put them at risk of poor psychosocial outcomes and impaired health-related quality of life (HRQOL). This study describes the protocol of a randomized controlled trial to evaluate the efficacy of Bright IDEAS-Young Adults (Bright IDEAS-YA), a problem-solving skills training intervention, on psychosocial outcomes of young adults newly diagnosed with cancer.</p></div><div><h3>Methods</h3><p>Bright IDEAS-YA is a two-arm, parallel, randomized controlled trial. Young adults are eligible if they are 18–39 years of age, within four months of a first cancer diagnosis, and receiving systemic therapy with life expectancy of at least six months. Participants are randomized 1:1 to Bright IDEAS-YA or enhanced usual care. Survey measures are completed at enrollment and 3, 6, 12, and 24 months. The primary endpoint will be the estimated change from baseline to 6 months in symptoms of depression, anxiety, and psychosocial HRQOL. The other time points are secondary endpoints. Mediators and moderators will be examined.</p></div><div><h3>Conclusions</h3><p>This randomized trial will determine the efficacy of Bright IDEAS-YA on psychosocial outcomes for young adults newly diagnosed with cancer. Analyses will also examine mechanisms of action and potentially identify subgroups for whom the intervention is particularly useful.</p></div><div><h3>Trial registration</h3><p><span><span>clinicaltrials.gov</span><svg><path></path></svg></span> #<span><span>NCT04585269</span><svg><path></path></svg></span>.</p></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901172","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":"A clinical trial inclusion criteria to enrich for patients presenting with canonical symptom structure in bipolar depression","authors":"","doi":"10.1016/j.cct.2024.107644","DOIUrl":"10.1016/j.cct.2024.107644","url":null,"abstract":"<div><p>Clinical drug development in psychiatry is challenging due to heterogeneous patient populations and the uncertainty of measuring neuropsychiatric constructs with symptom rating scales. Here we describe the development and implementation of an enrichment algorithm that identifies canonical versus anomalous symptom presentations, at the individual subject level, based on MADRS ratings obtained at screening and baseline. Data from 5 randomized, placebo-controlled, phase 3 trials in bipolar I disorder was used (<em>N</em> = 2026 subjects and 15,239 MADRS assessments). A variance-covariance difference (VCD) vector was developed to encode individual symptom structure using the 10 items of MADRS from the two sequential assessments. An anomaly score, calculated from each subject's VCD vector was derived by isolation forest to quantify the degree of disparity from the hypothesized canonical item structure. A retrospective application of the algorithm reliably identified a threshold anomaly score above which the psychometric properties of MADRS deteriorate. Consistent with increasing the certainty of MADRS ratings, subjects with a canonical symptom structure at baseline demonstrated greater effect sizes post-baseline in a phase 2 placebo-controlled trial of non-racemic amisulpride (SEP-4199) for bipolar depression, analyzed retrospectively. Our analyses show that the developed algorithm can reduce the symptom structure heterogeneity at baseline and thus improve the measurement certainty of psychiatric symptoms in clinical trials. This novel enrichment method has been prospectively implemented in a Phase 3 clinical study of SEP-4199 and is consistent with regulatory guidelines aimed at increasing the statistical power and lowering patient-burden in clinical trials.</p><p>Clinical Trials Registry: <span><span>NCT00868452</span><svg><path></path></svg></span>, <span><span>NCT00868699</span><svg><path></path></svg></span>, <span><span>NCT01284517</span><svg><path></path></svg></span>, <span><span>NCT01986101</span><svg><path></path></svg></span>, <span><span>NCT03543410</span><svg><path></path></svg></span>, <span><span>NCT05169710</span><svg><path></path></svg></span></p></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888704","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":"Exercise effects on brain health and learning from minutes to months: The brain EXTEND trial","authors":"","doi":"10.1016/j.cct.2024.107647","DOIUrl":"10.1016/j.cct.2024.107647","url":null,"abstract":"<div><p>Despite evidence that aerobic exercise benefits the aging brain, in particular the hippocampus and memory, controlled clinical trials have not comprehensively evaluated effects of aerobic exercise training on human memory in older adults. The central goal of this study was to determine chronic effects of moderate-to-vigorous intensity aerobic exercise on the hippocampus and memory in non-demented, inactive adults ages 55–80 years. We determine effects of aerobic exercise training with a 6-month randomized controlled trial (RCT) comparing 150 min/week of home-based, light intensity exercise with progressive moderate-to-vigorous intensity aerobic exercise. For the first time in a large trial, we examined temporal mechanisms by determining if individual differences in the rapid, immediate effects of moderate intensity exercise on hippocampal-cortical connectivity predict chronic training-related changes over months in connectivity and memory. We examined physiological mechanisms by testing the extent to which chronic training-related changes in cardiorespiratory fitness are a critical factor to memory benefits. The <em>Exercise Effects on Brain Connectivity and Learning from Minutes to Months</em> (Brain-EXTEND) trial is conceptually innovative with advanced measures of hippocampal-dependent learning and memory processes combined with novel capture of the physiological changes, genetic components, and molecular changes induced by aerobic exercise that change hippocampal-cortical connectivity. Given that hippocampal connectivity deteriorates with Alzheimer's and aerobic exercise may contribute to reduced risk of Alzheimer's, our results could lead to an understanding of the physiological mechanisms and moderators by which aerobic exercise reduces risk of this devastating and costly disease.</p></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878506","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":"Methods for assessing inverse publication bias of adverse events","authors":"","doi":"10.1016/j.cct.2024.107646","DOIUrl":"10.1016/j.cct.2024.107646","url":null,"abstract":"<div><p>In medical research, publication bias (PB) poses great challenges to the conclusions from systematic reviews and meta-analyses. The majority of efforts in methodological research related to classic PB have focused on examining the potential suppression of studies reporting effects close to the null or statistically non-significant results. Such suppression is common, particularly when the study outcome concerns the effectiveness of a new intervention. On the other hand, attention has recently been drawn to the so-called inverse publication bias (IPB) within the evidence synthesis community. It can occur when assessing adverse events because researchers may favor evidence showing a similar safety profile regarding an adverse event between a new intervention and a control group. In comparison to the classic PB, IPB is much less recognized in the current literature; methods designed for classic PB may be inaccurately applied to address IPB, potentially leading to entirely incorrect conclusions. This article aims to provide a collection of accessible methods to assess IPB for adverse events. Specifically, we discuss the relevance and differences between classic PB and IPB. We also demonstrate visual assessment through contour-enhanced funnel plots tailored to adverse events and popular quantitative methods, including Egger's regression test, Peters' regression test, and the trim-and-fill method for such cases. Three real-world examples are presented to illustrate the bias in various scenarios, and the implementations are illustrated with statistical code. We hope this article offers valuable insights for evaluating IPB in future systematic reviews of adverse events.</p></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859247","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":"Design and methods of the StepByStep randomized trial of a mobile health and social media physical activity intervention among adolescent and young adult survivors of childhood cancer: A report from the Children's Oncology Group","authors":"","doi":"10.1016/j.cct.2024.107645","DOIUrl":"10.1016/j.cct.2024.107645","url":null,"abstract":"<div><h3>Background</h3><p>Interventions to increase physical activity are needed in adolescent and young adult survivors of childhood cancer who are largely inactive but at lifelong elevated risk of multiple chronic conditions improved by physical activity. The goals of the StepByStep study are to evaluate the effects of a 48-week distance-based, multi-component mobile health and social media behavioral intervention on physical activity, biomarkers of cardiometabolic health, and health-related quality of life.</p></div><div><h3>Methods</h3><p>This ongoing study is a two-arm, prospective, multi-site randomized controlled trial. 384 childhood cancer survivors age ≥ 15 years and &lt; 21 years who were 3–36 months off therapy and not meeting physical activity guidelines were enrolled. The trial will test the efficacy of a 24-week intensive multi-component physical activity intervention combining a wearable physical activity tracker, social media peer support group, and individualized goal setting followed by a 24-week maintenance phase of the intervention to improve outcomes. The control group receives the wearable physical activity tracker only.</p></div><div><h3>Conclusion</h3><p>There is a growing need for novel, developmentally appropriate interventions to increase physical activity and improve the health trajectory of adolescent and young adult survivors of childhood cancer. If efficacious, this portable and scalable intervention would be a much-needed tool to reduce the morbidity from cancer treatment and improve quality of life among survivors after treatment ends.</p></div><div><h3>Clinical trial registration</h3><p><span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> Identifier: <span><span>NCT04089358</span><svg><path></path></svg></span>; COG Identifier: ALTE2031.</p></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141845383","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":"Design of the FRESH-teen study: A randomized controlled trial evaluating an adapted emotion regulation weight loss program for adolescents with overweight or obesity and their parent","authors":"","doi":"10.1016/j.cct.2024.107640","DOIUrl":"10.1016/j.cct.2024.107640","url":null,"abstract":"<div><p>Overweight and obesity affect &gt;40% of adolescents. Family-based behavioral treatment (FBT) is the most efficacious behavioral treatment for weight management among youth and consists of nutrition and physical activity education, behavior change skills, and parent skills training. However, the efficacy of FBT decreases for youth as they get older. Increased emotional lability and limited emotion regulation skills may contribute to the reduced efficacy of FBT for adolescents. To date, there are no treatments for overweight or obesity specifically adapted for the needs of adolescents.</p><p>We developed a treatment that integrates components from Dialectical Behavior Therapy and Emotion Focused Therapy with FBT (FBT+ER or FBT-ER) to address the specific needs of adolescents. The current study randomized 166 adolescents (BMI = 32.8; 14.3 years; 57% female; 32% Hispanic, 50% Non-Hispanic White, 18% Non-Hispanic and Non-White) and one of their parents (BMI = 32.9; 45.3 years; 85% female; 27% Hispanic, 57% Non-Hispanic White, 16% Non-Hispanic and Non-White) to 6 months of either standard FBT or FBT+ at 2 sites. Assessments were conducted at baseline, mid-treatment (month 3), post-treatment (month 6), 6-month follow-up (month 12) and 12-month follow-up (month 18). Primary outcomes are adolescent weight (BMIz/%BMIp95), emotion regulation skills, and emotional eating behaviors. Given the public health concern of adolescent obesity, FBT+ could prove extremely useful to provide more targeted and effective intervention for adolescents with overweight or obesity.</p></div><div><h3>Clinical trials</h3><p># NCT03674944</p></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141846965","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":"eMPower: An online Mind-body wellness Program for adults living with chronic health conditions: A three-armed randomized controlled trial protocol","authors":"","doi":"10.1016/j.cct.2024.107642","DOIUrl":"10.1016/j.cct.2024.107642","url":null,"abstract":"<div><h3>Background</h3><p>Symptoms of depression and anxiety are prevalent among adults with chronic health conditions, contributing to reduced quality of life, morbidity, and mortality. Mind-body wellness interventions (i.e. psychology programming, mindful movement, breathwork, meditation) may impact mental health symptoms, with online delivery offering access and scalability. Whether online mind-body wellness interventions are effective in improving patient outcomes across a broad range of chronic conditions remains uncertain.</p></div><div><h3>Methods</h3><p>This three-armed, pragmatic, randomized controlled trial will use a nested mixed methods approach to assess the effectiveness of an online mind-body wellness intervention (eMPower), offered at two levels of personnel support, on symptoms of anxiety and depression in adults with chronic health conditions. Inclusion criteria require a self-reported chronic condition and access to an internet-connected device. Eligible participants will be randomized 1:1:1 to [1] waitlist control; [2] eMPower; [3] eMPower + weekly 1-to-1 check-in. The primary analysis will compare the Hospital and Anxiety Depression Scale (HADS) total score between eMPower + weekly 1-to-1 check-in versus controls, with secondary and exploratory outcomes including HADS subscales, health-related quality of life, fatigue, program engagement, and frailty.</p></div><div><h3>Conclusion</h3><p>With online intervention delivery, a range of outcomes, mixed method evaluation, and automated intervention tracking, findings are anticipated to enhance our understanding of how individuals living with chronic health conditions engage with and are impacted by online mind-body wellness programming. Six hundred and fifty-six participants have been enrolled as of April 5, 2024, and 598 patients have completed 12-week follow-up.</p></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141839680","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":"Preventable sources of bias in subgroup analyses and secondary outcomes of randomized trials","authors":"","doi":"10.1016/j.cct.2024.107641","DOIUrl":"10.1016/j.cct.2024.107641","url":null,"abstract":"<div><h3>Background</h3><p>Randomized controlled trials are the gold standard for determining treatment efficacy in medicine. To deter harmful practices such as p-hacking and hypothesizing after the results are known, any analysis of subgroups and secondary outcomes must be documented and pre-specified. However, they can still introduce bias (and routinely do) if they are not treated with the same consideration as the primary analysis.</p></div><div><h3>Methods</h3><p>We describe several sources of bias that affect subgroup and secondary outcome analyses using published randomized trials and causal directed acyclic graphs (DAGs).</p></div><div><h3>Results</h3><p>We use the RECOVERY and START trials to elucidate sources of bias in analyses of subgroups and secondary outcomes. Chance imbalance can occur if the distribution of prognostic variables is not sought for any given subgroup analysis as for the main analysis. This differential distribution of prognostic variables can also occur in analyses of secondary outcomes. Selection bias can occur if the subgroup variable is causally related to staying in the trial. Given loss to follow up is not normally addressed in subgroups, attrition bias can pass unnoticed in these cases. In every case, the solution is to take the same considerations for these analyses as we do for primary analyses.</p></div><div><h3>Conclusions</h3><p>Approval of treatments and clinical decisions can occur based on results from subgroup or secondary outcome analyses. Thus, it is important to give them the same treatment as primary analyses to avoid preventable biases.</p></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792129","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":"Increasing goals of care conversations in primary care: Study protocol for a cluster randomized, pragmatic, sequential multiple assignment randomized trial","authors":"","doi":"10.1016/j.cct.2024.107643","DOIUrl":"10.1016/j.cct.2024.107643","url":null,"abstract":"<div><h3>Background</h3><p>Goals of care conversations explore seriously ill patients' values to guide medical decision making and often inform decisions about life sustaining treatments. Ideally, conversations occur before a health crisis between patients and clinicians in the outpatient setting. In the United States Veterans Affairs (VA) healthcare system, most conversations still occur in the inpatient setting. Strategies are needed to improve implementation of outpatient, primary care goals of care conversations.</p></div><div><h3>Methods</h3><p>We plan a cluster randomized (clinician-level) sequential, multiple assignment randomized trial to evaluate the effectiveness of patient implementation strategies on the outcome of goals of care conversation documentation when delivered in combination with clinician implementation strategies. Across three VA healthcare system sites, we will enroll primary care clinicians with low rates of goals of care conversations and their patients with serious medical illness in the top 10th percentile of risk of hospitalization or death. We will compare the effectiveness of sequences of implementation strategies and explore how patient and site factors modify implementation strategy effects. Finally, we will conduct a mixed-methods evaluation to understand implementation strategy success or failure. The design includes two key innovations: (1) strategies that target both clinicians and patients and (2) sequential strategies with increased intensity for non-responders.</p></div><div><h3>Conclusion</h3><p>This study aims to determine the effect of different sequences and combinations of implementation strategies on primary care documentation of goals of care conversations. Study partners, including the VA National Center for Ethics in Health Care and Office of Primary Care, can consider policies based on study findings.</p></div>","PeriodicalId":10636,"journal":{"name":"Contemporary clinical trials","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792128","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}