Background Community-based mental health interventions hold potential to reach communities who are less likely to engage in traditional clinic-based services. Partnering with community members and organizations to develop a community-informed approach increases the likelihood of successful implementation of these interventions. We will evaluate the effectiveness and implementation of an adapted mindfulness-based stress reduction intervention among Black/African American adults with comorbid depression and hypertension. Methods This trial is a single-arm, type 1 hybrid effectiveness-implementation study. We will recruit Black/African American adults (≥18 years) with elevated depressive symptoms (PHQ-9 scores ≥10) and a self-reported diagnosis of hypertension. All participants will be enrolled in an 8-week mindfulness-based stress reduction program that has been adapted for Black/African American adults, heart health, and community-based delivery. Study participants will complete surveys at baseline and at 4 weeks and 8 weeks post-baseline; blood pressure readings before and after the first and final mindfulness sessions; and a post-intervention focus group. We will also recruit community members to a community advisory board to advise on trial execution, challenges, implementation, and evaluation. Primary effectiveness outcomes include effect sizes of changes in depressive symptoms (Patient Health Questionnaire-9 scores) and systolic blood pressure from baseline to 8 weeks. The primary implementation outcome of implementation acceptability, appropriateness, feasibility will be assessed using mixed qualitative-quantitative methods. Discussion Successful completion of this trial will provide preliminary evidence for the effectiveness of mindfulness for improving depression and blood pressure control as well as the implementation of community-based mindfulness programs. Trial registration ClinicalTrials.gov (NCT06987799)
Posttraumatic stress disorder (PTSD) remains prevalent and disabling, especially among veterans, with a substantial proportion failing to achieve remission following first-line evidence-based trauma-focused psychotherapies. 3,4-Methylenedioxymethamphetamine (MDMA) is hypothesized to enhance psychotherapy outcomes through effects on fear extinction, cognitive flexibility, and emotional engagement, and is being studied as a promising augmentation strategy for PTSD psychotherapy. There is limited research combining MDMA with evidence-based PTSD treatment. MDMA-assisted psychotherapy trials to date have also been limited by lack of an active comparator and functional unmasking. We describe the methodology of an ongoing randomized, double-masked, pilot trial evaluating massed prolonged exposure (PE) therapy enhanced with MDMA for PTSD (aMETEMP), adapted for a U.S. Veterans Affairs outpatient setting. Up to 20 veterans with PTSD in the VA will receive a 6-8hr in-person MDMA dosing session (randomized dose 35 mg - 125 mg) integrated with a 3-week massed exposure protocol. The remaining visits are virtual and include PE sessions and sessions to prepare for and process the MDMA session (28-30hrs total over 11 visits), with the use of telehealth intended to improve access and ease patient burden. After treating the first 4 participants, who were fully informed of the trial design, we switched to using an incomplete disclosure strategy (not disclosing the number of treatment arms or specific possible doses) to further improve masking. Primary outcomes include PTSD severity using the Clinician-Administered PTSD Scale for DSM-5, safety, feasibility, and masking success. Findings are intended to provide preliminary descriptive information regarding feasibility, safety/tolerability, masking integrity, and symptom-change signals for aMETEMP with incomplete disclosure in a large outpatient healthcare system. ClinicalTrials.gov Identifier NCT06117306.
Introduction Hematopoietic cell transplantation (HCT) is a key treatment for patients with hematological malignancies, but often results in adverse effects that impact both physical and psychological well-being. This calls for the development of interventions aiming at reducing psychosocial impact of HCT. Among interventions, nature exposure appears promising and efficient via virtual reality. Combined to techniques increasing attention resources allocated to positive elements such as hypnosis, it could represent an innovative solution to preserve quality of life. Following the ORBIT model for the development of non-pharmacological interventions, this study constitutes a Phase IIc efficacy trial. It aims to evaluate the relative efficacy of an intervention combining virtual exposure to nature and hypnosis in patients with a hematological malignancy treated with HCT compared to observation only. Methods and analysis The intervention will consist of 2 to 3 weekly 30-min sessions over 2 weeks during aplasia following stem cell infusion, with immersive virtual nature exposure to environments (beach, forest) combined with hypnosis. Eligible patients will be randomly assigned to an intervention or control group. Participants in the intervention group will receive sessions between day +7 and day +21 after HCT. Primary outcome will be the change in quality of life from T1 to T2. Perspectives The results of this study will be highly relevant to determine the efficacy of a non-invasive and cost-effective intervention aimed at preserving QoL in patients treated with HCT. Demonstrating its efficacy will pave the way for further development and implementation of a future Phase III randomized controlled trial. Ethics and dissemination The project was approved by the Research Ethics Committee of Hôpital Maisonneuve-Rosemont (Project no 2026-4116). Participants will be asked to provide written consent for their participation. Results from this study will be shared through peer-reviewed publications, as well as oral and poster presentations at scientific events. The protocol for this study was preregistered on ISRCTN and raw anonymized data will be available on Open Science Framework (https://osf.io/n598j). Trial registration number ISRCTN42049015 (date of registration: November 6th, 2025). Protocol version 1 (01/11/2025).
Background Perimenopausal syndrome (PMPS) refers to a series of physiological and psychological symptoms caused by the fluctuation or decline of sex hormone levels during the pre- and postmenopausal periods. With the acceleration of aging society, more and more women suffer from symptoms of PMPS. Jinfeng Pill (JFP) is a classic Chinese patent medicine for gynecological diseases, but it lacks rigorous clinical evidence for the treatment of PMPS. Methods/design This randomized, double-blind, placebo-controlled, multicenter trial will be conducted across three hospitals in China. A total of 100 perimenopausal women will be randomly allocated in a 1:1 ratio to receive JFP or placebo for 12 weeks, followed by a 4-week post-treatment follow-up. The primary outcome is the modified Kupperman Index (KI), assessed at baseline and at weeks 4, 8, 12, and 16. Secondary outcomes include the Hot Flash scale (HFs), the Menopause-Specific Quality of Life (MENQOL) questionnaire, the Hamilton Depression Rating Scale (HAMD), the Hamilton Anxiety Rating Scale (HAMA), the Vaginal Health Index Score (VHIS), and Traditional Chinese Medicine (TCM) symptom score. Mechanistic outcomes encompass serum sex hormones and estrogen metabolites, inflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), gut microbiota composition (16S rRNA sequencing), faecal β-glucuronidase (β-GUS) activity, and short-chain fatty acid (SCFA) concentrations. Conclusion This is the first multicenter, randomized, double-blind, placebo-controlled trial to investigate the molecular mechanism by which JFP ameliorate PMPS by reshaping the gut microbiota structure, modulating β-GUS activity, optimizing SCFAs metabolism, suppressing inflammatory responses, and maintaining estrogen homeostasis. The results of this trial will help us to evaluate the efficacy, safety and possible mechanism of JFP in treating PMPS. Ethics and dissemination The protocol (Version 3.0, dated November 19, 2025) was approved by the Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (approval number: TJ-IRB202512083). Written informed consent will be obtained from all participants prior to enrolment. Findings will be disseminated through peer-reviewed publications and academic conference presentations. Trial registration number NCT07606755 (https://clinicaltrials.gov/study/NCT07606755).
Background/aims Randomized controlled trials (RCTs) with binary endpoints often face limitations in statistical power due to small sample sizes. Two strategies to improve efficiency are covariate adjustment using prognostic scores and borrowing information from historical control data. This simulation study compares the performance of these approaches under varying trial conditions. Methods We conducted simulations calibrated to parameters from three ulcerative colitis trials (QUASAR, UNIFI, VEGA). We assessed eight statistical methods: Cochran-Mantel-Haenszel (CMH); covariate-adjusted logistic regression model (Logit); prognostic score-adjusted linear probability model (PSA-LPM); prognostic score-adjusted G-computation (PSA-Gcomp); Two-Step frequentist dynamic borrowing; and three Bayesian borrowing approaches–normalized power prior (Bayes-NPP), empirical power prior (Bayes-EP), and robust meta-analytic predictive prior (Bayes-MAP). We varied treatment effect size; control response rate; prognostic score strength; and between-trial heterogeneity. The estimand was the marginal risk difference under a treatment-policy strategy. Results Logit, PSA-Gcomp, and PSA-LPM consistently improved power relative to CMH while generally maintaining appropriate type I error. Their performance was broadly comparable across the evaluated scenarios. Bayesian borrowing methods provided substantial power gains under low heterogeneity but showed increased bias and inflated type I error as heterogeneity rose. Bayes-NPP and Two-Step were highly sensitive to discordance between current and historical data, reducing reliability under moderate-to-high heterogeneity. Bayes-MAP demonstrated greater robustness to these changes. Conclusions Prognostic score adjustment provides a reliable and efficient alternative to historical borrowing, particularly when between-trial heterogeneity is present, that performs as well as other covariate adjustment methods. Bayesian borrowing methods can deliver large power gains when historical and current data are well-aligned, but require careful evaluation of prior compatibility and heterogeneity to preserve validity.
