Clinical Research Directory

A Study of a Deuterated Psilocin Analog (CYB003) in Humans With Major Depressive Disorder

The purpose of this study is to determine the efficacy, safety and tolerability of CYB003 compared to matching placebo as adjunctive treatment in patients with MDD. For more information about the EMBRACE study, including participating study locations, and to register your interest in learning more about participation, please visit the study website: https://embrace-mdd-trial.com/

Organizational Strategies and Psychosocial Skills for Maintaining Physical Activity After a Depressive Episode: a 3-month Post-rehabilitation Study.

With nearly 280 million people affected worldwide (2022), the management of depression represents a major public health issue. The study titled "Organizational Strategies and Psychosocial Skills to Maintain Physical Activity after a Depressive Episode: A 3-Month Post-Rehabilitation Study" (AP\&Depression) fits within this context. Physical activity (PA) is now recognized as an effective complementary therapy to pharmacological and psychotherapeutic treatments, helping to regulate mood and reduce depressive symptoms. However, despite these proven benefits, individuals who have experienced a depressive episode often struggle to maintain regular physical activity once they leave the hospital setting. This study aims to identify the mechanisms that influence the continuation of PA after hospitalization by exploring organizational strategies, psychosocial skills, and individual determinants involved in this process. Depression is a debilitating illness characterized by persistent sadness, loss of interest, chronic fatigue, and impaired cognitive and physical abilities (DSM-5, 2013). Among the aggravating factors, sedentary behavior plays a key role, whereas PA is associated with a significant reduction in the risk of relapse. Yet, 67.8% of individuals with depression do not meet the recommended 150 minutes of weekly PA, and this figure rises to 85.7% when activity is measured objectively. This situation is explained by several barriers: lack of motivation, low self-efficacy, fluctuating mood disorders, social isolation, and limited access to exercise facilities. Conversely, certain factors facilitate the resumption of PA after a depressive episode, including structured support, the establishment of routines, social support, and therapeutic education. The study relies on a qualitative methodology using semi-structured interviews conducted with 15 patients who stayed at the Rehabilitation Center of the Clinique des Portes de l'Eure. Participants are selected according to the following criteria: aged over 18, medically diagnosed with a depressive episode, underwent rehabilitation, and completed an initial assessment at the Maison Sport Santé. They will be interviewed three months after discharge to explore their PA practices. Data will be analyzed using NVivo software, following the COREQ (Consolidated Criteria for Reporting Qualitative Research) guidelines. The analysis of transcripts will help identify the organizational strategies implemented, the psychosocial skills involved, and the individual determinants influencing the maintenance of regular PA. The expected results should highlight that patients adopt various strategies to maintain PA after hospitalization. Session planning, the gradual integration of PA into daily life, and the anticipation of obstacles are major levers for establishing a sustainable routine. In addition, psychosocial skills, such as stress management and interaction with a support network, emerge as essential elements for maintaining regular physical activity. However, several obstacles may be identified, including persistent fatigue, mood fluctuations, lack of organization, and social isolation. These findings underscore the importance of personalized support after rehabilitation, particularly through mechanisms such as Patient Therapeutic Education (PTE) or individualized follow-up in Maisons Sport Santé. The aim of this study is to shed light on the mechanisms that enable individuals who have experienced a depressive episode to autonomously maintain physical activity after hospitalization. This research seeks to provide concrete recommendations for improving support during and after hospitalization to enhance adherence to PA. The study's conclusions could contribute to the development of new therapeutic approaches aimed at improving patients' quality of life.

The Lucida Project

The purpose of this clinical trial is to learn about the impact of the Healthy Minds Program (HMP) on measurements of well-being. The main question it aims to answer is: * Does use of HMP reduce symptoms of depression? Participants will complete a 4-week well-being program.

Inflammatory Pathways Modulated by Prenatal Mindfulness: A Route to Improve Maternal Child Emotional Well Being and Whole Person Health

The goal of this study is to investigate inflammation as the biological mechanism by which mindfulness based cognitive therapy for perinatal depression (MBCT-PD) administered during pregnancy improves women's emotional well-being and whole person health index during pregnancy and the early postpartum period. Secondarily the investigative team will determine if MBCT-PD administered during pregnancy improves the physical health and emotional well-being of the developing child.

Mindfulness-Integrated Neuropsychotherapy for Traumatic Brain Injury: A Mixed-Methods Evaluation of Cognitive and Psychosocial Recovery

The goal of this clinical trial is to test the effectiveness of Integrative Mindfulness Enhanced Neuropsychotherapy (IMENP) in improving neurocognitive functioning and wellbeing among adults aged 18 to 44 years with mild to moderate Traumatic Brain Injury (TBI). The main questions it aims to answer are: * Does IMENP improve neurocognitive functioning in individuals with mild to moderate TBI? * Does IMENP improve quality of life, and reduce depression and fatigue in individuals with mild to moderate TBI? Researchers will compare participants who receive the 16 session IMENP programme to participants on a waitlist control condition to see if IMENP improves cognitive functioning and overall wellbeing. Participants in the experimental group will: Attend 16 sessions of IMENP delivered twice weekly over three months Complete mindfulness practices, cognitive rehabilitation exercises, and emotional regulation techniques during sessions Complete between session homework tasks including expressive writing, mindful activities, and reflective exercises Be assessed on neurocognitive functioning, quality of life, depression, and fatigue at baseline, post intervention, and one month follow up Participants in the waitlist control group will: Receive treatment as usual during the three month intervention period Be assessed at the same time points as the experimental group Receive three introductory IMENP sessions following study completion

Targeted ACT Compared to Supportive Therapy for Depression RCT

Acceptance and Commitment Therapy (ACT) has demonstrated efficacy in reducing depressive symptoms, primarily compared to no treatment or minimal treatment controls. This study compared the efficacy of ACT targeting cognitive defusion (CD, 3 sessions) and values-based activity scheduling (VBAS, 3 sessions) to supportive therapy (ST). Both treatments offered six sessions, a rationale for the approach, related techniques, and homework assignments. A parallel group randomized controlled efficacy trial design was used. Participants were stratified by gender identification and depression severity and then randomly allocated, according to a predetermined sequence, 2:1 to ACT or ST. Dependent measures were collected during acute treatment (pre, mid, and post-treatment) and follow-up at one-month.

Psychological Prehabilitation for Complex Gastrointestinal Surgery

The goal of this clinical trial is to learn if a psychological program before surgery can help adults who have lasting stress from past medical experiences. The program is called PREPARE-GI. It is for adults having planned, complex surgery on the digestive system, also called gastrointestinal (GI) surgery. Many people who need complex GI surgery have been through a lot. They may have had many surgeries, hospital stays, or emergency visits. These experiences can leave lasting stress, worry, and low mood. These feelings can make recovery from surgery harder. The main questions this study aims to answer are: * Can researchers sign up enough participants, and will participants attend the program sessions and finish the surveys? * Does the program lower stress, worry (anxiety), and low mood (depression)? * Does the program lower pain and improve quality of life after surgery? * Does the program shorten hospital stays or lower return visits to the hospital or emergency room? Researchers will compare two groups. One group will take part in the PREPARE-GI program. The other group will get usual surgical care. Participants will be placed in a group by chance, like flipping a coin. Adults may be able to join if they: Are 18 or older Have complex GI surgery planned at Northwestern Memorial Hospital at least 8 weeks away Score high on a short survey about stress from past experiences Can complete the study in English All participants will: Answer survey questions about stress, worry, mood, body symptoms, pain, and quality of life. They will do this before surgery, then 1 month and 3 months after surgery. The surveys will take about 20 to 30 minutes to complete. Rate their pain on a scale from 0 to 10 after surgery. Allow researchers to review their medical records for information about their surgery and recovery. Participants in the program group will also meet one-on-one with a licensed psychologist for 8 sessions. Each session lasts about 1 hour and will take place either in person or by secure video from home. In the sessions, participants will learn skills to manage stress, handle difficult feelings, and prepare for surgery and recovery. Participants will be in the study for about 5 months. Participants in the program group will spend about 9 to 10 hours on the study. Participants in the usual care group will spend about 1 to 1.5 hours. This is a small study with 20 participants. The results will help researchers plan a larger study in the future.

GynMDD Add-On to Supportive Psychotherapy in Mild to Moderate Depression

The goal of this clinical trial is to learn whether the dietary supplement GynMDD, when taken as an add-on to supportive psychotherapy, can improve symptoms of mild to moderate depression in adults aged 18 to 65. The main questions it aims to answer are: Does adding GynMDD to supportive psychotherapy lead to a greater reduction in depressive symptoms (measured by the MADRS scale) compared with supportive psychotherapy plus placebo? Does the supplement also improve digestive well-being and influence gut microbiota profiles over the course of treatment? Researchers will compare patients receiving supportive psychotherapy + GynMDD to those receiving supportive psychotherapy + placebo to see if GynMDD provides additional benefits beyond standard care. Participants will: * Attend regular appointments with their general practitioner * Complete one supportive psychotherapy session per week for 8 weeks * Take a daily dose of GynMDD or placebo * Complete weekly self-assessment questionnaires on mood, digestive symptoms, and any side effects via a mobile app * Provide two stool samples (at the start and end of the study) for microbiota analysis

Effects of Mindfulness and Self-regulation Training on Anxiety, Depression, PTSD, and Leadership

The goal of this study is to measure the effects of Mindfulness-based Mind Fitness Training (MMFT) on anxiety, depression, post-traumatic stress disorder, sleep quality, and leadership.

A Non-Interventional Pilot Study to Explore the Role of Gut Flora in Disease

This study seeks to correlate microbiome sequencing data with information provided by patients and their medical records.

Screening and Monitoring of Mental Health in Educational Settings: Programme for Detection, Psychoeducation and Self-help

Adolescence is a critical developmental stage during which many mental health problems first emerge. However, a large proportion of these issues go undetected and untreated. Globally, approximately one in seven adolescents experiences mental health difficulties, with increasing trends observed in recent years. Schools offer an important setting for early detection and intervention, yet existing programmes often lack structure or scalability. The MENTOR programme (MENtal Health Tracking, Outreach and Referral) was designed to identify adolescents under psychological distress in educational settings and offer tiered support including psychoeducation, self-help tools, and referral to mental health services when needed. This is a prospective, longitudinal, multicentre study that will be implemented in eight educational centres in Spain, including secondary schools, sixth-form colleges, and vocational training centres. Adolescents and young adults will be invited to participate voluntarily. At baseline and at each trimester, participants will complete validated mental health screening tools assessing common conditions such as anxiety, depression, and emotional dysregulation. Based on results, participants will be assigned to one of several support pathways: access to digital self-help materials, small-group interventions, or referral to school-based or external mental health professionals. Follow-up assessments will measure changes in symptomatology, engagement with self-care tools, and help-seeking behaviour. Quantitative data will be analysed to assess feasibility, adherence, and effectiveness of the intervention over time, and conduct a cost-effectiveness analysis This protocol aims to improve adolescent mental health through a school-based, digitally delivered screening and intervention programme. By evaluating feasibility and acceptance across eight educational centres, the study seeks to generate real-time data on prevalent mental health issues, promote awareness and self-care, and facilitate early professional intervention. If effective, the programme could support scalable, tiered prevention strategies in educational settings, contributing to reduced rates of anxiety, depression, suicidal ideation, eating disorders, and addictions. Its implementation may also improve resource allocation, reduce wait times, and inform future health policies for longitudinal mental health monitoring from childhood. Findings will contribute to the development of accessible, evidence-based models for adolescent mental health promotion and early intervention.

Transcranial Electrical Stimulation for Comorbid Depression and Chronic Pain

The goal of this clinical trial is to learn if active transcranial alternating current stimulation (tACS) and transcranial direct current stimulation (tDCS) can improve pain symptoms in patients with major depressive disorder (MDD) and chronic pain symptoms. It will also explore the neural mechanisms underlying these potential effects. The main questions it aims to answer are: 1. Are there any differences in the overall efficacy among the three intervention groups (tACS, tDCS, and sham)? 2. Is active tACS superior to sham stimulation in reducing pain symptoms in patients with MDD and chronic pain over the 2-week treatment period and at the 6-week follow-up? 3. Is active tACS superior to active tDCS in reducing pain symptoms? 4. Does active tACS, compared to tDCS, demonstrate a more persistent improvement in pain symptoms, as measured at the 6-week follow-up? 5. As an exploratory objective, what neural oscillation entrainment mechanisms underlie the potential analgesic effects of tACS? Researchers will compare three parallel groups: active tACS, active tDCS, and sham stimulation, to evaluate their efficacy. All three groups are randomized and double-blinded. In addition, a separate exploratory open-label cohort of 10 participants will receive the same active tACS intervention while performing a cognitive task. This exploratory arm is designed to investigate the neural oscillation entrainment effects of tACS. Data from this arm will be analyzed separately and are not included in the primary confirmatory analyses. Participants in the main randomized trial will: 1. Receive 40 minutes of stimulation (tACS, tDCS, or sham) once daily, 5 days per week, for 2 weeks (10 sessions total). 2. Complete clinical assessments and cognitive tests at baseline, mid-intervention (week 1), post-intervention (week 2), and at a 6-week follow-up. 3. Undergo resting-state functional MRI (rs-fMRI) and blood sample collection at baseline and post-intervention for exploratory biomarker analyses. Participants in the exploratory open-label arm will: 1. Receive active tACS (1 mA, 10 Hz, 40 minutes) once daily, 5 days per week, for 2 weeks (10 sessions total), while performing a cognitive task during stimulation. 2. Complete resting-state and task-state EEG recordings at the following time points: (1) At baseline (pre-intervention) (2) Immediately before and after the 1st tACS session (3) Immediately before and after the 10th tACS session (4) On the day after completion of all 10 sessions These EEG recordings are designed to assess: (1) the immediate entrainment effects of a single tACS session, (2) the cumulative effects after repeated tACS sessions, and (3) the persistent neural plasticity changes following the full intervention course.

Maintenance Individualized Neuromodulation and Depression-detection Via Sensors for Early Treatment

This proposal seeks to carry out a prospective, single-arm open label study aimed at sustaining treatment-resistant depression (TRD) response in patients with TRD who had responded to prior individualized resting-state functional connectivity (rs-FC)-guided intermittent theta burst stimulation (iTBS). It also seeks to detect and predict relapse risk by integrating rs-FC iTBS with a TMS-adapted needs-based symptom-titrated algorithm based longitudinal ECT (STABLE) maintenance scheduling algorithm, and passive digital biomarkers.

Mapping the Neural Circuits of Depression and Anxiety Using Personalized, Accelerated TMS and Deep Phenotyping

This proposal seeks to carry out a double-blinded, randomized, comparative study that investigates neurobehavioral changes induced by personalized, anxiosomatic and dysphoric network guided accelerated intermittent-theta burst (iTBS) using dense functional Magnetic Resonance Imaging (fMRI) sampling in participants with treatment-resistant depression (TRD) and moderate/high levels of anxiety.

Mpata Yathu Trial for Young Women in Zambia

This randomized controlled trial evaluates Mpata Yathu ("Our Space"), a trauma-informed, church-based counseling intervention for adolescent girls and young women in Lusaka, Zambia who have experienced gender-based violence and are living with or at risk for HIV. The intervention is delivered by lay counselors who provide individual problem-solving therapy and referrals for mental health, HIV, and GBV-related services. Participants are assigned to receive counseling immediately or after a three-month waitlist period. The study examines mental health, HIV-related outcomes, and the feasibility, acceptability, and fidelity of delivering this community-based intervention.

Modulatory Effects of Personalized Transcranial Magnetic Stimulation (TMS) on Heart-Brain Coupling in Individuals With Depressive Tendencies

This study focuses on individuals with depressive tendencies and investigates the regulatory effects of Transcranial Magnetic Stimulation (TMS)-guided by personalized functional connectivity mapping-on heart-brain coupling in this population, while also exploring the underlying mechanisms.Participants will undergo 3T functional magnetic resonance imaging (fMRI) scans, followed by four different types of neurostimulation: stimulation targeting individualized Dorsolateral Prefrontal Cortex (DLPFC) -Subgenual Anterior Cingulate Cortex (sgACC) functional connectivity, stimulation targeting individualized DLPFC-insula functional connectivity, standard F3 targeting, and sham stimulation. The order of these stimulation sessions will be randomized. Researchers will simultaneously record the participants' electroencephalogram (EEG) and electrocardiography (ECG) signals before and after stimulation, and will record ECG in real-time during the stimulation. The primary objective of this study is to investigate the effects of DLPFC targeting specificity on metrics such as heart-brain coupling in individuals with depressive tendencies, thereby providing a basis for future research on objective assessment and personalized interventions for depression.

Exercise Adherence in Afghan Women With Depression

The goal of this clinical trial is to learn whether a structured, culturally adapted home-based exercise program helps Afghan women with depression stay more active than routine exercise advice. The study will also examine whether taking part in the exercise program improves depression symptoms, daily functioning, and participant satisfaction, and whether the program is safe. The main questions the study aims to answer are: * Does a structured home-based exercise program help participants exercise more regularly over 8 weeks? * Does the program improve depression symptoms and daily functioning? * Is the program acceptable to participants, and are there any safety concerns? Researchers will compare a structured home-based exercise program with routine exercise advice to see which approach leads to better exercise adherence. About 60 women aged 18 to 50 years with mild to moderate depression will take part. Participants will be randomly assigned (by chance) to one of two groups. Participants in the structured exercise group will: * Receive an illustrated exercise booklet with simple home-based exercises, such as breathing, stretching, walking, and light aerobic activities. * Choose exercises that suit their preferences, abilities, and daily schedules. * Record each exercise session in a logbook, including the date, type of exercise, and how long they exercised. Participants in the routine exercise advice group will: * Receive their usual psychiatric care and general advice about the benefits of physical activity. * Receive a logbook to record any physical activity or exercise they complete during the study. All participants will take part in the study for 8 weeks. At the beginning and end of the study, they will complete questionnaires about their depression symptoms and their ability to carry out everyday activities. At the end of the study, participants will also complete a questionnaire about their satisfaction with the program, and researchers will ask about any medical problems or injuries that occurred during the study. The information from this study may help researchers understand whether a culturally adapted home-based structured exercise program is a practical and effective way to support Afghan women with depression and encourage regular physical activity.

Estimation of Control Before and After Treatment of a Depressive Episode With Serotonin Reuptake Inhibitors

The goal of this observational study is to better understand cognitive and affective processes involved in depression, in particular how individuals estimate their perception of control over events in their environment, as well as related processes such as memory and decision-making. The study also aims to investigate how these processes are affected by antidepressant treatment and how depressive symptoms evolve over time, as well as whether specific peripheral markers (including hormones) are associated with treatment effects.

The COMET Study: a Prospective COhort of MEdical residenTs to Assess Professional, Personal and Psychological Trajectories of Residents in General Internal Medicine

Introduction. Switzerland, like most Western countries, faces a paradox: an ageing, multimorbid population needs general internal medicine (GIM) physicians more than ever, yet fewer young doctors choose - and stay in - the specialty. Career decisions during residency are intertwined with well-being, mental and physical health, and work-life balance, and distress in training has been associated with depression, burnout, attrition and poorer patient care. Longitudinal data following GIM residents across these domains, and linking them to actual career trajectories, are lacking. The COMET study establishes a multicentre prospective cohort of GIM residents to fill this gap. Methods and analysis. COMET is a prospective, open, multicentre cohort conducted in the departments of (general) internal medicine of Fribourg Hospital (HFR, four sites), Bern University Hospital (Inselspital) and Lausanne University Hospital (CHUV). All GIM residents providing direct patient care are eligible (≈334 residents; expected enrolment ≥267, assuming 80% participation). Participants complete an annual online survey (REDCap; French or German) at baseline and for at least four years, covering sociodemographics; job characteristics; career intentions and 24 factors for or against a GIM career; well-being (Physician Well-Being Index, Professional Fulfillment Index, quality of life, work-life balance); mental health (CES-D, Perceived Stress Scale, Maslach Burnout Inventory, Questionnaire of Cognitive and Affective Empathy); and physical health (step counts, physical activity, fatigue, sleep, healthcare utilisation). Primary endpoints are the longitudinal course of well-being and distress (PWBI, PFI, CES-D) and residents' career trajectory. Analyses combine descriptive statistics, mixed-effects and regression models, and comparisons with the population-based CoLaus\|PsyCoLaus cohort.

Comparing the Efficacy of Heated Yoga and Sauna as a Treatment for Depression

This project explores whether heated yoga, sauna, and a mindfulness app reduce depressive symptoms

Lonely in Depression

The goal of this prospective study is to better understand the link between loneliness and depression in the inpatient psychiatric treatment of depression. It aims to answer: Do lonely and not lonely persons benefit the same way from inpatient depression treatment? Is loneliness a clinical relevant factor in inpatient treatment of depression? What are the underlying biopsychosocial mechanisms? Participants will be asked to do some * self-report questionnaires * clinical interview * biosampling (blood, saliva, stool) at three main measurement timepoints (1. begin of inpatient treatment, 2. day of discharge, 3. three months after discharge).

VOCALE LBD: Online Peer Support for Caregivers of People With Lewy Body Dementia

This study tests whether a tailored, fully asynchronous online group intervention (VOCALE LBD) reduces depression in family caregivers of people with Lewy Body Dementia (LBD), compared to standard educational materials. LBD is the second most common form of degenerative dementia and causes distinct challenges, including visual hallucinations, REM sleep disorder, and severe motor symptoms, that are not addressed by generic caregiver interventions. Depression rates in LBD caregivers reach 40-50%, double the rate seen in Alzheimer's disease caregivers, yet no rigorous digital interventions exist specifically for this population. VOCALE LBD is a text-based, low-bandwidth platform (Discourse) that brings groups of 10-15 caregivers together in an 8-week moderated online community. Weekly topics address LBD-specific challenges (sleep problems, hallucinations, self-care) and problem-solving skills using the ADAPT method. A pilot study (n=54) showed strong effects on depressive symptoms (Cohen's d=0.54 at 1-month follow-up), near-perfect engagement, and high participant satisfaction. This RCT (N=220) will test efficacy, examine mechanisms of action (self-efficacy and problem-solving), and explore analytics approaches for pragmatic monitoring, laying groundwork for future implementation in clinics and community organizations.

Improving Patient Engagement in Mental Health Services

Hybrid Type II Implementation Trial

The Effects of Chiropractic on Adults With Depression

The goal of this clinical trial is to evaluate the feasibility of the study design in preparation for a future clinical trial examining chiropractic care for adults with mild to moderate depression. We aim to determine whether the study procedures function as intended, including the ability to recruit, retain, and engage participants, as well as whether the intervention is implemented as planned. The main questions it aims to answer is: 1. Can sufficient eligible participants be enrolled within the planned timeframe? 2. Is there any retention of participant throughout the study duration and the factors contributing to ongoing participation? 3. Can participants adhere to pre-treatment instructions and protocols before their first check-up? 4. Can participants attend and complete all assessments and chiropractic sessions? 5. Can participants fulfill all required study activities without excessive burden? 6. Can chiropractors strictly follow chiropractic adjustments only, without offering any additional treatments? Researchers will compare adults with depression on the waitlist group to see if chiropractic care effects on adults with depression. Participants will * Perform resting state Electrocardiography (ECG) * Perform resting state Electroencephalography (EEG) * Perform Event-related potential (ERP) à Auditory and visual stimuli tests * Complete Patient Reported Outcomes (PROs) * COMPASS-31 * PROMIS-29 * PROMIS-Cog-8 * Perceived Stress Scale * Depression Short Form 8a * Complete Assessment of Acceptability * Complete Columbia Suicide Severity Rating Scale (C-SSRS) * Receive 6 weeks of chiropractic care treatment