Registered studies, protocols and reported results
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Registered studies, protocols and reported results
Clinical study protocols and source-reported registry results, preserved locally.
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Registered studies, protocols and reported results
Study registrations describe protocols. Results are shown only when the registry supplied a Results section; local links are not efficacy claims.
31 exact matches
Snapshot 14/09/2026Major Depressive Disorder
Open study recordLate-Life Depression (LLD), or depression in older adults, often presents with motivational deficits, deficits in performance in cognitive domains including processing speed and executive dysfunction, and mobility impairments. This triad of findings implicate dopaminergic dysfunction as a core pathophysiologic feature in depression, and may contribute to cognitive decline and motor disability. Normal aging results in brain-wide dopamine declines, decreased D1/D2 receptor density, and loss of dopamine transporters. Although brain changes associated with depression and aging converge on dopamine circuits, the specific disturbances in LLD and how responsive the system is to modulation remain unclear. In this study, investigators are testing integrative model that aging, in concert with pro-inflammatory shifts, decreases dopamine signaling. These signally changes affects behaviors supported by these circuits, in the context of age-associated cortical atrophy and ischemic microvascular changes, resulting in variable LLD phenotypes. Investigators propose a primary pathway where dopaminergic dysfunction in depressed elders contributes to slowed processing speed and mobility impairments that increase the effort cost associated with voluntary behavior. The central hypothesis of this study is that late-life depression is characterized by dysfunction in the dopamine system and, by enhancing dopamine functioning in the brain. By improving cognitive and motor slowing, administration of carbidopa/levodopa (L-DOPA) will improve depressive symptoms. Late Life Depression (LLD) is a prevalent, disabling, and at times lethal condition for which currently available treatments are often ineffective. No prior study has comprehensively examined dopamine-dependent behaviors (i.e., reward processing, cognition, motor function) in LLD, and none has integrated positron emission tomography (PET), multimodal magnetic resonance imaging (MRI), neuropsychological evaluation, and mobility assessments. Should cognitive and motor slowing result in altered effort-based decision making as researchers hypothesize, treatment development may shift from addressing mood and hedonic responses toward facilitating cognition and movement, reducing the effort cost of voluntary behavior, and promoting behavioral activation. This study, across collaborative sites, will enroll 100 evaluable elderly depressed outpatients who enter baseline study procedures and who exhibit evidence of dopaminergic dysfunction, characterized as either slowed processing speed or slowed gait speed. To disentangle depression effects from age-related changes, 70 never-depressed elders also will complete baseline evaluation. To achieve this goal, at Vanderbilt University Medical Center (VUMC) the investigators will enroll 80 depressed elders and 50 never-depressed elders who complete baseline study procedures. The University of Pittsburgh Medical Center will enroll an additional 20 depressed elders and 20 never-depressed elders who complete baseline study procedures. Assessments include PET imaging of receptor density, neuromelanin-sensitive MRI (NM-MRI) measurement of nigrostriatal status, task-based MRI focused on effort-based decision making and reward processing, and comprehensive psychiatric, neurocognitive, and physical performance evaluation. Depressed participants then will be randomized to levodopa (L-DOPA) or placebo for 3 weeks, followed by repeat multimodal MRI and cognitive/behavioral assessments. In a cross-over phase, participants will receive the opposite intervention for an additional 3 weeks followed by clinical and cognitive assessments only. This mechanistic probe allows the investigators to examine the contributions and interrelationships of dopamine-dependent processes in LLD and evaluate the responsivity of dopamine systems in LLD to pharmacological stimulation. AIM 1: To characterize dopaminergic dysfunction in LLD at molecular, circuit, and behavioral levels. Hyp 1: Compared to age- and gender-matched controls on baseline functional MRI (fMRI), LLD participants will be less willing to expend effort for rewards and exhibit lower prefrontal cortex and striatal activation on the Effort Expenditure for Rewards Task (EEfRT). Hyp 2: Across all participants, lower striatal \[18F\]-FDOPA relative influx rate, lower midbrain \& striatal \[18F\]-fallypride binding, and lower NM-MRI signal in the substantia nigra, pars compacta will predict lower performance across RDoC domains: Positive Valence (impaired willingness to expend effort, decreased neural activations on the EEfRT), Cognitive (slowed processing speed and executive dysfunction), and Sensorimotor (slowed gait speed). Hyp 3: Across all participants, slowed processing and gait speed likewise will predict lower willingness to expend effort on the EEfRT. AIM 2: To examine responsivity of dopamine circuits in LLD to stimulation with L-DOPA. Hyp 1: Compared to placebo, L-DOPA will result in greater normalization of neural activations and improved behavioral performance in Positive Valence, Cognitive, and Sensorimotor domains. Hyp 2: Baseline PET and NM-MRI measures will moderate L-DOPA effects. The greatest improvements will be observed in those with the lowest baseline \[18F\]-FDOPA relative influx rate, \[18F\]-fallypride binding, and NM-MRI signal. Exploratory Aims: 1) To investigate associations of baseline proinflammatory markers with dopaminergic function across molecular, circuit, cognitive and behavioral levels of analysis. 2) To evaluate the durability of L-DOPA effects on RDoC domains in the crossover phase.
Major depressive disorder is one of the leading causes of disability worldwide, and a substantial proportion of patients do not achieve adequate improvement with conventional antidepressant treatments. Cannabidiol (CBD), a non-intoxicating cannabinoid derived from Cannabis sativa, has shown potential anxiolytic, anti-inflammatory, and neurobiological effects that may be relevant for depressive disorders. The ANANDA trial is a multicenter, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy, safety, and tolerability of full-spectrum cannabidiol oil as an adjunctive treatment in adults with treatment-resistant major depressive disorder. A total of 120 participants will be randomly assigned to receive either full-spectrum cannabidiol oil or placebo for 12 weeks while maintaining stable antidepressant treatment. Clinical assessments of depressive symptoms, anxiety, sleep quality, perceived stress, and adverse effects will be performed at baseline, Week 4, and Week 12. Blood samples will be collected at baseline and after 12 weeks to investigate inflammatory and neuroendocrine biomarkers. The primary objective is to evaluate changes in depressive symptoms after 12 weeks of treatment. Secondary objectives include the assessment of anxiety, sleep quality, perceived stress, biological markers, safety, and tolerability. The findings of this study may contribute to the development of new therapeutic approaches for treatment-resistant depression and provide additional evidence regarding the clinical use of cannabidiol in psychiatric disorders. Major depressive disorder (MDD) is a highly prevalent psychiatric condition and one of the leading causes of disability worldwide. Despite the availability of several antidepressant treatments, approximately one-third of patients do not achieve adequate symptom remission after multiple treatment attempts, characterizing treatment-resistant depression. This condition is associated with substantial functional impairment, reduced quality of life, increased healthcare utilization, and elevated suicide risk. The endocannabinoid system has emerged as a promising target for the treatment of mood disorders because of its involvement in emotional regulation, stress response, neuroplasticity, neuroinflammation, and neurotransmitter modulation. Cannabidiol (CBD), a non-intoxicating phytocannabinoid derived from Cannabis sativa, has demonstrated anxiolytic, anti-inflammatory, neuroprotective, and antidepressant-like effects in preclinical studies, while preliminary clinical evidence suggests potential benefits in psychiatric disorders. The ANANDA trial is a multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial designed to evaluate the efficacy, safety, and tolerability of full-spectrum cannabidiol oil as adjunctive therapy in adults with treatment-resistant major depressive disorder. The study will be conducted at the University of Southern Santa Catarina (UNISUL) and the Federal University for Latin American Integration (UNILA). A total of 120 participants diagnosed with treatment-resistant major depressive disorder will be randomized in a 1:1 ratio to receive either full-spectrum cannabidiol oil or placebo for 12 weeks while maintaining stable antidepressant treatment. Randomization will be performed using a computer-generated allocation sequence. Participants, investigators, healthcare providers, outcome assessors, and members of the research team responsible for participant follow-up and data analysis will remain blinded to treatment allocation throughout the study period. The placebo formulation will be matched to the active intervention in appearance, color, packaging, and administration conditions to maintain blinding. Clinical evaluations will be performed at baseline, Week 4, and Week 12 using validated instruments for depressive symptoms, anxiety, sleep quality, perceived stress, adverse effects, and quality of life. Biological samples will be collected at baseline and after 12 weeks of treatment to assess inflammatory and neuroendocrine biomarkers potentially associated with treatment response. The primary outcome is the change in depressive symptom severity measured by the Montgomery-Åsberg Depression Rating Scale after 12 weeks of treatment. Secondary outcomes include changes in anxiety symptoms, sleep quality, perceived stress, biological markers, safety, and treatment tolerability. The results of this study may contribute to a better understanding of the therapeutic potential of cannabidiol in treatment-resistant depression and may provide evidence to support future clinical applications of cannabinoid-based interventions in psychiatry.
Open study recordThis is UG3 phase of a multi-site, milestone-driven UG3/UH3 research program evaluating pregnenolone for individuals with co-occurring cannabis use disorder (CUD) and major depressive disorder (MDD). Pregnenolone is a neurosteroid that modulates cannabinoid receptor signaling and may reduce cannabis-related effects while also improving mood-related symptoms. The primary objective of the UG3 phase is to establish feasibility and generate preliminary data to support a subsequent UH3 randomized clinical trial. Key preparatory activities include obtaining regulatory approvals (including FDA Investigational New Drug \[IND\] protocol amendment and Institutional Review Board approvals), harmonizing study procedures across participating sites, and implementing data management and monitoring systems. The UG3 phase includes two main components. First, a pharmacokinetic study willcharacterize pregnenolone pharmacokinetics in adults with CUD and MDD, including measures such as half-life and clearance. Second, a pilot clinical study will evaluate the feasibility, safety, and tolerability of pregnenolone administered orally over approximately 12 weeks. Feasibility outcomes include recruitment rates, retention, and adherence to study procedures, while safety and tolerability will be assessed through adverse event monitoring and discontinuation rates. Participants will be adults aged 18 to 50 years with diagnoses of cannabis use disorder and major depressive disorder, who report frequent cannabis use and express interest in reducing their use. Clinical assessments of cannabis use, mood symptoms, and related behavioral outcomes will be collected. The UG3 phase will be used to refine study procedures, inform dosing strategies, and establish benchmarks necessary for progression to the UH3 phase. The subsequent UH3 phase will involve a multi-site, randomized, double-blind, placebo-controlled trial evaluating the efficacy of pregnenolone in reducing cannabis use and improving depressive symptoms in this population. This study represents the UG3 phase of a multi-site, milestone-driven UG3/UH3 research program evaluating pregnenolone as a novel pharmacotherapy for individuals with co-occurring cannabis use disorder (CUD) and major depressive disorder (MDD). Pregnenolone is a neurosteroid that modulates cannabinoid receptor signaling and may reduce cannabis-related effects while also improving mood-related symptoms. The primary objective of the UG3 phase is to establish feasibility and generate preliminary data to support a subsequent UH3 randomized clinical trial. Key preparatory activities include obtaining regulatory approvals (including FDA Investigational New Drug \[IND\] protocol amendment and Institutional Review Board approvals), harmonizing study procedures across participating sites, and implementing data management and monitoring systems. The UG3 phase includes two main components. First, a pharmacokinetic study will be conducted to characterize pregnenolone pharmacokinetics in adults with CUD and MDD, including measures such as half-life and clearance. Second, a pilot clinical study will evaluate the feasibility, safety, and tolerability of pregnenolone administered orally over approximately 12 weeks. Feasibility outcomes include recruitment rates, retention, and adherence to study procedures, while safety and tolerability will be assessed through adverse event monitoring and discontinuation rates. Participants will be adults aged 18 to 50 years with DSM-5 diagnoses of cannabis use disorder and major depressive disorder, who report frequent cannabis use and express interest in reducing their use. Standardized clinical assessments of cannabis use, mood symptoms, and related behavioral outcomes will be collected. Data obtained during the UG3 phase will be used to refine study procedures, inform dosing strategies, and establish benchmarks necessary for progression to the UH3 phase. The subsequent UH3 phase will involve a multi-site, randomized, double-blind, placebo-controlled trial evaluating the efficacy of pregnenolone in reducing cannabis use and improving depressive symptoms in this population.
Open study recordThe goal of this clinical trial is to learn if Therabot-CALM (Cannabis, Anxiety, Low Mood) has acceptability among users and could work to improve the symptoms of persons with cannabis use disorder and anxiety and/or depression. The main question it aims to answer is: What is the usability, feasibility, and acceptability of Therabot-CALM in persons with Cannabis Use Disorder and Anxiety and/or Depression? Participants will * Take a screening questionnaire * Participate in two virtual 1-hour interviews to provide feedback on app design and suggest features. * Engage with Therabot-CALM in a 4-week clinical trial and provide feedback on their app experience in a third virtual interview Participants will complete a two-stage screening process via REDCap to determine their eligibility for enrollment. Participants who meet criteria and provide informed consent will be enrolled and participate in three interviews and the 4-week clinical trial. After the first interview, researchers will fine-tune Therabot-CALM based on feedback received during the interview. After the second interview, experts by experience (EBEs) will engage with Therabot-CALM at least once per day for 4 weeks. After the clinical trial period, participants will receive an email with a link to complete the post-intervention measures delivered via REDCap, including the System Usability Scale (SUS), Treatment Acceptability and Adherence Scale (TAAS), Cannabis Use Disorders Identification Test - Revised (CUDIT-R), the Daily Sessions, Frequency, Age of Onset, and Quantity of Cannabis Use Inventory (DFAQ-CU), the 9-item Patient Health Questionnaire for depression (PHQ-9), and the 7-item generalized anxiety disorder screener for DSM-5 (GAD-7). Participants will then be asked to return for a third interview to provide feedback on their experience with Therabot-CALM. Researchers will use the IDEAS (Innovate, Develop, Evaluate, Adapt, Scale) Impact Framework to plan and conduct three, one-on-one interviews with a trained research assistant (RA). Each interview script will be developed using the IDEAS Impact Framework and follow a semi-structured design, such that the RA will follow a set of questions, with as-needed probing for follow-up. Interviews will be recorded via a virtual platform.
Open study recordThe goal of this phase 1 study is to investigate the safety and efficacy of dimethyltryptamine (DMT) in individuals with depression and healthy controls. We hypothesize that administration of DMT will result in decreases in depression, associated symptoms, and neuroplastic changes in depressed subjects. We expect that DMT will induce changes in neuroplasticity as indexed using electroencephalographic (EEG) measures and tasks in both depressed individuals and healthy volunteers, though to different degrees. These neuronal changes may in parallel cause changes in mood measured both in healthy and depressed subjects, which will be captured using appropriate psychometric measures of mood.
Open study recordSince the COVID-19 pandemic, mental health disorders have increased significantly, particularly among young people. In France, the proportion of young people aged 18 to 25 suffering from depression almost doubled between 2017 and 2021. This phenomenon particularly affects students, who are already identified as being at greater risk of mental health disorders than the general population. Medical students seem to be particularly vulnerable: in 2021, a national study showed very high rates of depression and suicidal thoughts in this population. The main factor associated with depression was the feeling of financial hardship. Students often face multiple forms of insecurity. Financially, they have limited resources and struggle to cover their basic needs such as housing, food and healthcare. Socially, many experience significant isolation, particularly when they are away from their families or under pressure from their studies. All of this has a significant impact on their mental health. Unfortunately, many students do not seek help due to lack of time, resources, or awareness of support services. The 2021 study showed that only one-third of medical students suffering from depression received appropriate treatment. The aim of our study is to assess the impact of precariousness on the onset of psychiatric disorders and on the use or non-use of healthcare services. Our study will involve nearly 45,000 students from PSL and UPC universities. It is based on a longitudinal cohort (via questionnaires) over three years. The aim is to identify precisely the different aspects of student precariousness (housing, transport, isolation, economic difficulties, etc.) and their link with psychological distress. The study will measure the extent of the phenomenon and identify modifiable factors that could be targeted by preventive measures. The results will enable us to better target preventive measures and propose concrete solutions to improve students' well-being and promote their success. The COVID-19 pandemic has led to an increase in depression, particularly among young people. The French health barometer, conducted every 4-5 years by Santé Publique France (SPF), found that the prevalence of major depressive episodes (MDE) among 18-25 year olds doubled (from 11.7% to 20.8%) between 2017 and 2021. There has also been an increase in suicidal thoughts and suicide attempts. Among students, data from the 2016 Student Life Observatory (OVE) found a higher prevalence of CDE and suicidal thoughts among students than in the general population of the same age. Among the factors associated with the risk of EDC, experiencing significant financial difficulties was the main one\[4\]. Among medical students, a national study conducted in 2021 found that the prevalence of depression and suicidal thoughts was much higher than in the general population of the same age. Financial difficulties were also the main factor associated with the risk of depression. Indeed, students are a population that is particularly vulnerable to precariousness due to several factors. Economically, they often have limited incomes, depending on parental support, insufficient grants or precarious jobs. This exposes them to difficulties in meeting their basic needs such as housing, food and healthcare. Socially, isolation can exacerbate their situation, especially when they are far from their family network or under pressure from their studies. In addition, high academic demands, combined with unstable living conditions, impact their mental health and can contribute to the development of psychiatric disorders, which often go untreated due to a lack of affordable and accessible resources. International students are even more vulnerable due to language and administrative barriers and limited access to local support services. This multidimensional precariousness highlights the need for comprehensive support for this population, even though students are unlikely to seek professional help. In the 2021 survey, only 32% of medical students suffering from depression received adequate care. If we want to improve the health of medical students, we must not only treat disorders, but also prevent them from occurring by helping students strive for a state of well-being. In terms of prevention, the Haute Autorité de Santé (HAS) distinguishes between three levels: primary prevention, which acts upstream of the disease (on risk factors); secondary prevention, which acts at an early stage of its development (screening); and tertiary prevention, which acts on complications and the risk of recurrence. The objectives of the study are to identify and quantify the modifiable predictive and moderating factors explaining students' psychological distress that could give rise to (primary) prevention actions by studying the various components of precariousness (housing, transport, study conditions, social isolation, grants, etc.). It also aims to study the impact of the various components of precariousness on the use and non-use of healthcare (screening and treatment, secondary and tertiary prevention). The data will be entered directly by participants on the SKEZIA platform (https://skezi.eu/) (a solution developed by SKEZI) co-founded by AP-HP and Paris-Cité University, and will be hosted on HDS-approved servers. Main objective: The objective is to explore the impact of precariousness on the risk of characterised depressive episodes and the use of healthcare among PSL students (17,000 students) and UPC health faculty students (28,000 students). Primary outcome measure: The study will assess the 12-month prevalence of: * characterised depressive episodes (using the Composite International Diagnostic Interview Short-Form (CIDI-SF)) and suicidal ideation in the same way as SPF and OVE; * use of healthcare services, which will be measured in a similar way to the OVE survey and the medical student survey. Precariousness will be assessed by the question: 'Would you say that you are currently experiencing financial difficulties?' Secondary objectives and evaluation criteria: The secondary objectives are to : * evaluate the prevalence of : * anxiety, which will be assessed using the GAD7; * eating disorders, which will be assessed using the SCOFF; * alcohol addiction, which will be assessed using the AUDIT, and cannabis addiction, which will be assessed using the CAST; * burnout, using the student version, which will be assessed using the MBI-SS for pre-clinical or healthcare students and the MBI-HSS for externs and residents, * dropout, which will be assessed by a single question as in the CNA-CORE survey, * insomnia, which will be measured by the Insomnia Severity Index (ISI), * loneliness, which will be assessed using the UCLA 3 items, * harassment, * discriminatory treatment, * and quality of life (WHOQOL); * identify and quantify modifiable predictive and moderating factors explaining students' psychological distress that could lead to (primary) prevention measures = by studying the various components of precariousness (housing, transport, study conditions, social isolation, grants, etc.), * study the impact of the various components of precariousness on the use and non-use of healthcare (screening and treatment, secondary and tertiary prevention). This will be assessed using questions on the renunciation of healthcare and its causes.
Open study recordThe purpose of this study is to examine the feasibility, acceptability, and preliminary efficacy of a digital intervention for co-occurring cannabis use and depression. Participants will be randomized to complete Amplification of Positivity - Cannabis Use (AMP-C) or symptom tracking. The main outcomes will include changes in depressive symptoms and cannabis use, as well as usability ratings.
Open study recordTrauma exposure, posttraumatic stress disorder (PTSD), and substance use disorder (SUD) present major threats to public health. PTSD and SUD are major correlates of disability, often resulting in severe social and occupational impairment. Comorbidity between PTSD and SUD (PTSD/SUD) is common and frequently co-occurs with other mental health ailments including depression, anxiety, and suicidality. Comorbidity may be amplified in groups vulnerable to high trauma exposure, such as women with low socioeconomic status including women experiencing homelessness (WEH). Moreover, the reciprocal nature of PTSD/SUD (substances are used to cope with PTSD symptoms; substance use can create high-risk situations for new traumas to occur), can create a cycle of trauma and symptomatology leading to a critical health disparity. PTSD/SUD can be costly and difficult to treat, with treatment completion often low and relapse rates often high. Low-cost, complementary interventions, such as self-compassion (SC) interventions, which target key mechanisms that maintain PTSD/SUD, could improve treatment outcomes. SC interventions include practices that build skills to improve emotional responses, cognitive understanding, and mindfulness. Recent research supports the benefit of SC interventions for reducing PTSD, SUD, and related comorbidities, potentially with large effects. However, sample sizes have generally been small and randomized designs infrequently used. Moreover, while SC interventions may act to improve key mechanisms of treatment response and/or symptom maintenance (e.g., emotion regulation/dysregulation, trauma-related guilt, trauma-related shame, moral injury, and craving), such mediating factors have been underexplored. To address these limitations, the present proposal will implement community-based research principles and use a two phase, mixed-method design to adapt and test a widely used SC intervention (Mindful Self Compassion; MSC) for use with a sample of WEH with PTSD/SUD. The project will be conducted in partnership with a state-funded drug treatment facility that serves women and families experiencing high health disparities. Phase I was completed in 2023 and adapted the standard MSC course for use with trauma-exposed WEH with PTSD/SUD using the ADAPT-ITT model, an eight-stage model that engages community partners to increase feasibility and acceptability of interventions for at-risk populations. Phase II will be an open-label cluster randomized clinical trial (N=202) to test the benefit of the adapted MSC at improving primary (PTSD, substance use) and secondary outcomes (depression, anxiety, hopelessness) among a sample of WEH with PTSD/SUD residing in a residential drug treatment site. MSC (n=101) will be compared to Treatment as Usual (TAU; n=101). WEH in the MSC group will complete a 6-week (six sessions plus a half-day retreat) MSC intervention. The TAU group will engage in weekly check-ins with the research team but will not receive an intervention. WEH will be assessed at baseline, immediately post-intervention, and at a 4-month follow-up. One-on-one interviews will be conducted with the MSC group to collect qualitative data on experiences. An exploratory aim will be to elucidate mechanism of treatment-response and maintenance or remission of PTSD symptoms. These potential mechanisms will include SC, emotion regulation/dysregulation, trauma-related guilt, trauma-related shame, moral injury, and craving. Results may inform treatment for PTSD/SUD in WEH and other groups experiencing high health disparities and provide valuable insights into mechanisms underlying PTSD/SUD symptoms over time. Findings are relevant to military populations, which experience high rates of PTSD/SUD, and other populations disproportionately exposed to trauma.
Open study recordDialectical behavior therapy (DBT) is a comprehensive, third-wave psychological intervention designed for patients with complex and severe behavioral, emotional, and interpersonal dysfunction. DBT has since been adapted to shorter, briefer, "skills training" formats, which have been effective for a number of mild-to-moderate mental health conditions, including depression and anxiety. Moreover, internet-delivered formats of DBT (iDBT) have similarly started to build support for their effectiveness, although there are fewer studies on digital formats. One study found that over 12 weeks, iDBT was deemed acceptable (e.g., 50% of participants were still active after 4 weeks) and there were improvements in multiple symptom domains, such as depression, anxiety, suicidality, functional disability, as well as alcohol and substance dependence. In the current study, the investigators will examine the feasibility, acceptability, and potential efficacy of a new iDBT intervention, packaged as an online e-learning skills course, with adult participants. The study is a pilot trial as iDBT has never been tested in this format through formal research. Thus, this pilot study aims to examine whether this course is usable, practical, and potentially useful to others in the future. The investigators will recruit up to 40 individuals with mild-to-moderate depression and anxiety for an 8-week study. Following a phone screen to determine eligibility, participants will complete a baseline session where they will provide consent, complete a brief interview and questionnaires, and register for the e-learning skills course. Over the course of 8 weeks, participants will be exposed to material adapted from a DBT manual in a self-guided manner. Participants will complete follow-up assessments at 4 and 8 weeks.
Open study recordThe present study aims to assess the feasibility of home-based tDCS in remote and urban areas (primary objective). The secondary aim is to obtain a preliminary assessment of the efficacy of 14 home-based tDCS sessions in reducing depressive symptoms in BPD patients with moderate to severe depressive episodes and BPD symptoms. Exploratory objectives include assessing the impact on neuropsychological and psychosocial functioning, anxiety, physical activity, sleep disorders, and addiction. Additionally, we aim to investigate the sociodemographic and clinical factors that are linked to the most favorable response to tDCS in addressing both depressive and BPD symptoms. We also aim to assess the feasibility of using a smartwatch as an outcome measure in this population. Finally, we intend to gather preliminary data on the effectiveness of an online psychoeducational program specifically designed for patients with BPD. Researchers will compare active tDCS to sham tDCS to see if active treatment is more effective in treating depression in this population. Participants will: * Receive 14 sessions of either active or sham tDCS over one week, delivered at home * Complete psychological and neurocognitive assessments at baseline, post-treatment, and at 6 weeks * Wear actigraphy monitors and complete questionnaires to assess sleep, physical activity, and other mental health outcomes This trial will also explore the feasibility of delivering tDCS in both urban and rural settings. Background Major Depressive Disorder (MDD) is the most common comorbidity among individuals with Borderline Personality Disorder (BPD), affecting over 85% of patients and leading to high recurrence rates and resistance to treatment. Traditional pharmacological and psychotherapeutic interventions often show limited efficacy in this population, highlighting the need for innovative treatment strategies. Emerging evidence suggests that the dorsolateral prefrontal cortex (DLPFC) plays a crucial role in the pathophysiology of both MDD and BPD. In addition, non-invasive brain stimulation, particularly transcranial Direct Current Stimulation (tDCS), has shown promising results in alleviating depression and improving BPD symptoms when targeting the DLPFC. The development of home-based tDCS presents new opportunities for accessible and cost-effective interventions. However, no study has specifically investigated its effects on MDD in the context of BPD. Methods This double-blind randomized controlled trial (RCT) will assess the efficacy of home-based tDCS in reducing depressive symptoms in BPD patients who are experiencing moderate to severe depressive episodes. A total of 60 participants will be randomized, following a two-week online psychoeducation, to receive either active or sham tDCS in 14 sessions over one week. The primary outcome is the feasibility of home-based tDCS in remote and urban areas. The secondary aim is to obtain a preliminary assessment of the efficacy of 14 home-based tDCS sessions in reducing depressive symptoms in BPD patients with moderate to severe depressive episodes and BPD symptoms. Exploratory analyses will evaluate the impact of tDCS on neuropsychological functioning, physical activity, and substance use. Sociodemographic variables will be considered in predicting treatment response. All assessments will be conducted at baseline, post-treatment, and during follow-ups up to three months after treatment ends. Discussion The findings will address the feasibility of tDCS in real-world settings, contributing to the development of scalable neuromodulation strategies for individuals with BPD and comorbid depression.
Open study recordA large body of evidence on depression heterogeneity point to an "immunometabolic" subtype characterized by the clustering of immunometabolic dysregulations with atypical behavioral symptoms related to energy homeostasis. Motivational and motor impairments reflected by symptoms of anhedonia and psychomotor retardation in major depression are closely related to alterations in energy homeostasis, are associated with increased inflammation, and may be a direct consequence of the impact of inflammatory cytokines on the dopamine system in the brain. In the proposed project, the investigators will examine the effect of dopamine stimulation on motivation and motor function in patients with major depression and healthy controls and the role of inflammation using a double-blind, randomized, placebo-controlled, cross-over design. If successful, this study would provide crucial evidence that pharmacologic strategies that increase dopamine may effectively treat inflammation-related symptoms of anhedonia and psychomotor retardation in major depression.
Open study recordThis study aims to identify the influence of social determinants of health domains on vascular function in a low income, racial, and ethnic minority population at risk for disparities. We hypothesize that individuals of a lower social economic position and those struggling with depression are at greater risk of cardiovascular disease. This study aims to identify the influence of social determinants of health domains on vascular function in a low income, racial, and ethnic minority population at risk for disparities. We hypothesize that individuals of a lower social economic position are at greater risk of impairment in the large organ that is responsible for blood movement in the body and artery stiffness. Additional sims include identifying the influence of depression on vascular function and measure the interaction between depression and social determinants of health. We hypothesize that impairment will be greater in individuals with depression than in individuals without. Finally we will compare a comprehensive metabolic project against the social determinants of health and depression, hypothesizing that more severe social determinants of health and depression will increase the risk of cardiovascular disease.
Open study recordThis single-site study is a pilot, three-armed, double-blinded, placebo-controlled randomized controlled trial (RCT) that will determine the feasibility of a definitive RCT investigating the use of cannabis oil as a treatment for insomnia in individuals with MDD. The study will also determine whether standard THC with higher CBD vs lower CBD has a differential impact on insomnia. The study will also analyze other important objective parameters of sleep including total sleep time and sleep efficiency from actigraphy data. Optional polysomnography data may also be collected and analyzed. In addition, standardized, validated instruments will be used to collect data on severity of depressive symptoms, cognitive functioning biological rhythm disruption, daytime sleepiness, health-related quality of life (HRQoL), healthcare resource utilization, work productivity and activity impairment, as well as other side effects, in order to better understand the potential impact of the use of cannabis oil on these important health outcomes. The study will be a three-arm, randomized, double-blind, placebo-controlled trial. The study population will include 60 males and females, ages 19 and older, who report chronic problems with insomnia at least three times per week for at least three months and have a diagnosis of co-morbid MDD. Eligible participants will complete a urine screen for drugs of abuse including opioids, cannabis, benzodiazepines and amphetamines before treatment randomization. Participants with a positive screen for any of these drugs of abuse will be excluded from the study. If the drug screen is negative, the principal investigator will assess patient health history and perform a physical examination. All study participants must be able to fully understand the study procedures and must sign a research ethics board (REB)-approved informed consent before study entry. A neuropsychological battery will be used to assess cognitive function in the domains of attention, verbal memory, psychomotor functioning, and executive functioning at baseline and at the end of the 4-week treatment in order to examine possible cognitive benefits or side effects from the treatment. These cognitive domains were chosen because these domains are known to be negatively affected by chronic insomnia and by cannabis use. Patients will also complete a series of clinician-rated and self-reported questionnaires. During the 4-week treatment period, participants will be instructed to start treatment with a single, dose of oil at bedtime. Each dose will have either 50 mg/ml CBD and 2 mg/ml THC (High CBD arm; MLP-001) or 10 mg/ml CBD and 2 mg/ml THC (Low CBD arm; MLP-002). Non-responding study participants will add 1 additional dose to their respective treatment after 2 weeks if a higher dosage is needed based on an Insomnia Severity Index (ISI) reduction of \>8 points and tolerability (side effects). Responding participants will continue with 1 dose of their treatment after 2 weeks. This dose range is based on previous studies showing that the effective dosage of THC to improve sleep ranged, on average, between 5 and 15 mg daily.
Open study recordThis study will evaluate the effectiveness of valbenazine on patient- and clinician-reported outcomes assessing health-related quality of life, functioning, and treatment effect in participants with tardive dyskinesia (TD) who are receiving valbenazine for up to 24 weeks.
Open study recordThe main objective of this study is to identify risk factors for depression among medical students by comparing them to students who completed their first year but did not enter the medical program (students not accepted into the second year of medical school). Major Depressive Disorder (MDD) will be assessed using a validated tool: the Composite International Diagnostic Interview Short-Form (CIDI-SF). This a prospective, longitudinal, cohort study. The plan is to inform each new cohort of students at the Orléans University Hospital medical school for 10 years. It is estimated that 5,000 to 10,000 students will be able to participate in the study. A link to access the study questionnaire will be sent to students by email via the registrar's office, with one email per week for four weeks. The email will contain a link to a web page where the questionnaire can be completed. The questionnaire will be available online on computers or smartphones for six weeks: from mid-October to the end of November. The questionnaire will be completed each year for the duration of the study or until the student completes their studies. Duration of the inclusion period: 10 years Duration of participation for each participant: maximum 12 years Total duration of the study: 22 years As the cohort progresses, longitudinal analyses may be conducted to study the evolution of various disorders over time, adjusting for known confounding factors. Following the initial analyses of this study, a new interventional study will be set up to identify students at risk and offer them appropriate care. The COVID-19 pandemic has led to an increase in depression, particularly among younger people. The French Health Barometer, conducted every 4-5 years by Santé Publique France (SPF), found that the prevalence of a major depressive disorder (MDD) among 18-25 years old doubled (from 11.7% to 20.8%) between 2017 and 2021. There has also been an increase in suicidal thoughts and suicide attempts. Among students, data from the 2016 of observatoire de la vie étudiante (OVE) showed a higher prevalence of MDD and suicidal thoughts among students compared to the general population of the same age group. For medical students, a national study conducted in 2021 revealed rates of depression and suicidal thoughts far exceeding those of the general population of the same age. Financial difficulties were the main factor associated with the risk of depression. Indeed, students are a particularly vulnerable population to precariousness due to several factors. Economically, they often have limited income, relying on parental support, insufficient scholarships, or precarious jobs. This exposes them to difficulties in meeting essential needs such as housing, food, and healthcare. Socially, isolation can worsen their situation, especially when they move away from their family network or faced with academic pressure. Furthermore, high academic demands combined with unstable living conditions affect their mental health and may contribute to the development of psychiatric disorders, often untreated due to lack of resources or accessible care. This multidimensional precariousness highlights the need for comprehensive support for this population, especially since students rarely seek professional help. In the 2021 survey, only 32% of medical students suffering from depression received adequate care. To improve the health of medical students, it is therefore not enough to treat disorders; we must also prevent their onset by helping students achieve a state of well-being. This a prospective, longitudinal, cohort study aims is to identify risk factors for depression among medical students by comparing them to students who completed their first year but did not enter in the medical program (students not accepted into the second year of medical school). The main objective of this study is to assess Major Depressive Disorder (MDD) using a validated tool : the Composite International Diagnostic Interview Short-Form (CIDI-SF). We will assess the 12-month prevalence of the main psychiatric disorders evaluated, dropout using a single question, and loneliness. Care utilization will be measured, as well as care avoidance and its causes, along with financial and social insecurity, educational satisfaction, and stigma. Additional variables or questionnaires may be added through protocol amendments. These measurements will be obtained through students filling out an online questionnaire. Quantitative analyses will be conducted, starting with univariate and then multivariate models, with adjustments for known confounding factors. The plan is to inform each cohort of students at the Orléans University Hospital medical school for 10 years. It is estimated that 5,000 to 10,000 students will be able to participate in the study. Each year, all medical students will be informed of the protocol at meetings at the University of Orléans at the start of the academic year in September regardless of their year of study (e.g. 1st year of medical study, 2nd, 3rd, 4th year of study etc…). The study will be offered each year to students entering PASS/LAS at the Faculty of Medicine of the University of Orléans and to cohorts that have already begun their medical studies. A link to access the study questionnaire will be sent to students by email via the registrar's office, with one email per week for four weeks. The email will contain a link to a Callyope platform where the questionnaire can be completed. Students will create an account using their university email address as their username. If the student does not object, they will have to answer the first question of the questionnaire and then complete the full online questionnaire on the Callyope platform. The questionnaire will be available online on computers or smartphones for six weeks: from mid-October to the end of November. The questionnaire will be completed each year between mid-October and the end of November for the duration of the study or until the student completes their studies. Duration of the inclusion period: 10 years Duration of participation for each participant: maximum 12 years Total duration of the study: 22 years As the cohort progresses, longitudinal analyses may be conducted to study the evolution of various disorders over time, adjusting for known confounding factors. Following the initial analyses of this study, a new interventional study will be set up to identify students at risk and offer them appropriate care.
Open study recordThis pilot clinical trial aimed to evaluate the short-term efficacy of Avatar therapy for treatment-resistant major depressive disorder Major depressive disorder (MDD) is among the most common and disabling mental health conditions worldwide. However, treatment-resistant major depressive disorder (TR-MDD) is a prevalent clinical challenge and public health concern. While various pharmacological and psychotherapeutic treatments are available, a significant proportion of individuals do not achieve adequate symptom relief. Indeed, approximately 30% to 55% of individuals with MDD remain symptomatic after two adequate antidepressant trials, and psychotherapy has shown only modest efficacy in treatment-resistant cases. In this context, our research team developed Avatar therapy, an approach using virtual reality as a therapeutic tool to treat TR-MDD. The Avatar Therapy for TR-MDD displays strong experiential and relational components that are crucially missing in conventional interventions. Throughout the 10 therapy sessions, participants were allowed to engage in a dialogue in virtual reality with an avatar representing a person who played a significant role in their depressive symptoms, which was animated in real-time by a therapist. The primary outcomes was severity of depressive symptoms. Secondary outcomes included severity of anxiety symptoms, self-esteem, quality of life and functioning. The investigators will also explore whether the greater improvements attributable to the Avatar Therapy persist in time. Given the high prevalence of individuals with TR-MDD and the negative repercussions for individuals, their entourage, and society, the current trial will contribute to the validation of a novel approach and create new therapeutic possibilities.
Open study recordSevere mental illness (SMI) refers to the most burdensome psychiatric conditions. The need to pre-empt the onset of SMI is pressing because once SMI develops, quality of life is poor and available treatments have limited efficacy. Most risk factors for SMI are either unchangeable (e.g., genetics) or difficult to alter (e.g., low socio-economic status). In contrast, cannabis use is one specific risk factor that could be avoided. Certain individuals are more vulnerable to the harmful effects of cannabis. Genetic factors can help us identify these high-risk individuals. One in three individuals are carriers of a higher-risk genetic variant, and cannabis users with this genotype are at up to 7-fold increased risk of developing schizophrenia. In our study, genetic counselling will be provided to participants by a board-certified genetic counsellor. During the genetic counselling session, participants will have the option to receive their genotype. Participants will be counselled regarding their individualized risk of developing and of not developing SMI based on family history, whether or not they choose to use cannabis, and genotype (if the participants accept the genetic test results). The investigators hypothesize that this intervention will reduce exposure to cannabis compared to the youth who are not offered the intervention. Severe mental illness (SMI) refers to the most burdensome forms of psychiatric disorder, including schizophrenia, bipolar disorder, and severe depression. These illnesses typically emerge in adolescence or young adulthood and are associated with substantial impairment in functioning. A significant proportion (\~30%) of individuals with SMI remain resistant to any form of available pharmacotherapy. The combination of early onset, poor response to treatment and persistent disability makes SMI the most problematic group of illnesses to individuals and society. The need for early interventions to pre-empt the onset of SMI is pressing because once SMI develops, quality of life is poor for patients and their families. There is substantial overlap in the genetic and environmental risk factors for individual forms of SMI, and predictors of SMI are not specific to any one disorder. It is therefore necessary to conceptualize SMI as transdiagnostic and include diagnoses of schizophrenia, bipolar disorder, and depression, rather than focusing on single illnesses when developing preventative interventions. Prevention of SMI is currently hindered by the inability to identify those at risk early enough to normalize their developmental trajectory. Recent advances in genomics and the understanding of important gene-environment interactions may help overcome this challenge and enable effective and targeted prevention of SMI. Cannabis exposure during critical periods of brain maturation is an avoidable environmental risk factor for SMI. A replicated gene-cannabis interaction shows that carriers of a common genetic variant (C alleles at rs2494732 in the AKT1 gene) are at up to 7-fold increased risk of developing psychosis if they use cannabis. Genetic counselling provides a powerful tool to communicate genetic information to youth in a way that empowers and enhances health. The present project involves the delivery of a genetic counselling intervention to inform youth of their personalized risk of developing SMI based on genotype, family history, and whether or not they choose to use cannabis. This project will be the first application of molecular genetic information and genetic counselling to prevent SMI. Aim: To test if genetic counselling regarding personalized risk information based on a replicated gene-cannabis interaction reduces cannabis use in youth at high risk of developing severe mental illness. Hypotheses: 1. A genetic counselling intervention will be acceptable to youth at high familial risk of SMI. 2. A genetic counselling intervention with personalized feedback of AKT1 genotype will reduce cannabis use among vulnerable youth. 3. The effect of the intervention will be moderated by AKT1 genotype, with greater reduction of cannabis use among carriers of the sensitive C alleles. Method: A cohort of over 450 youth (aged 3-29) has been enrolled as part of the Families Overcoming Risks and Building Opportunities for Well-being (FORBOW) study. The investigators have obtained biological samples for measurement of genetic variation and the investigators will obtain biological samples to measure cannabis exposure. The investigators will randomly select one in every two eligible youth (aged 12-21) to be offered genetic counselling during which the participants will be provided with personalized genetic information and they will be counselled regarding risk of developing SMI based on genotype, family history, and whether or not they choose to use cannabis. The investigators will follow the participants through the developmental period with the highest risk of cannabis use initiation and the investigators will assess cannabis use and psychopathology annually. The primary outcome will be abstinence from cannabis reported by participants in confidential interviews and confirmed by measurement of the primary metabolites of psychoactive Δ9-tetrahydrocannabinol in blood and urine samples. Significance: This project will realize the first translational application of a gene-environment interaction to improve mental health and test an intervention with potential public health benefits.
Open study recordThe prevalence of major depressive disorder (MDD) is \~5.0%, and rates of co-occurring SUDs in these patients approach 40-50%. Specifically, rates of co-morbid cannabis use disorder (CUD) in patients with MDD are elevated 2-3 fold compared to 2.9% in the general population, and is associated with poorer treatment outcomes and impaired cognitive and psychosocial functioning in comparison to MDD patients without CUD. Most studies of cannabis use in MDD are cross-sectional in design, and therefore causal relationships are unclear. This study investigates the effects of cannabis abstinence over a 28-day period in patients with MDD with co-occurring CUD using a randomized controlled design, namely contingent reinforcement. The prevalence of major depressive disorder (MDD) is \~5.0%, and rates of co-occurring SUDs in these patients approach 40-50%. Specifically, rates of co-morbid cannabis use disorder (CUD) in patients with MDD are elevated 2-3 fold compared to 2.9% in the general population, and is associated with poorer treatment outcomes and impaired cognitive and psychosocial functioning in comparison to MDD patients without CUD. To date, most studies of cannabis use in MDD were cross-sectional in design, and therefore causal relationships are unclear. The investigators previous studies in cannabis dependent patients with schizophrenia suggest that extended cannabis abstinence (up to 28 days) using contingent reinforcement is associated with improvements in specific areas of cognition (e.g. verbal learning and memory) and depressive symptoms. A more recent study using an open-label design demonstrated that 28 days of cannabis abstinence improves depressive symptoms and anhedonia in participants (N=11) with co-occurring MDD and CUD. The investigators propose a controlled cannabis abstinence paradigm in patients with co-morbid MDD and CUD (N=52) to further investigate these findings. Stabilized MDD patients with moderate to severe CUD will be randomly assigned to one of two groups: 1) A contingent reinforcement (CR) intervention (n=26); 2) a non-contingent reinforcement (NCR) intervention (n=26), which will serve as a time and non-abstinence control. In the CR group, subjects achieving biochemically-verified cannabis abstinence at study endpoint (Day 28) will receive a $300 contingent payment; participants in the NCR group will not receive this contingent payment. The primary outcomes are: 1) cannabis abstinence rates at Day 28 in CR versus NCR groups; 2) changes in mood (depressive), anxiety and sleep symptoms over the 28-day assessment period. Secondary outcomes include cognition.
Open study recordBackground Adults over the age of 60 with symptoms of major depressive disorder are said to have late-life depression (LLD), a condition that usually decreases a person's quality of life and is associated with other risks like physical frailty and dementia. A common feature of more severe LLD is psychomotor slowing, where a person's ability to think and move are impaired. For example, they might not be able to walk or process information as quickly, and they might have problems with their working memory. Psychomotor slowing in LLD might be the result of a problem with the way a person's body produces or responds to the neurotransmitter dopamine. The drug Levodopa (L-DOPA), which can replace missing dopamine in the brain, has been used to treat to treat Parkinson's disease for many decades, and it might also affect psychomotor slowing in LLD. Methods In this study, participants are adults aged 60 years or older with moderate to severe major depression. Participants undergo the "L-DOPA challenge"-a 2-week period where they receive a dose of L-DOPA once a day for the first week and a dose of L-DOPA twice a day for the second week. Before and after a participant completes the L-DOPA challenge, the study team assesses their depressive symptoms and psychomotor function. After the L-DOPA challenge, if a participant still shows signs of moderate or severe depression, they receive an antidepressant for 12 weeks. Aims The first aim of this study is to test the feasibility of the L-DOPA challenge-that is, whether most of the 50 participants recruited for this study will complete the L-DOPA challenge. For example, participants might have to withdraw if they can't make the daily visits to the research site to receive their L-DOPA medication, if they can't tolerate the medication's side effects, or if their depressive symptoms get significantly worse. Our hypothesis is that 80% of the participants will complete the L-DOPA challenge. The second aim of the study is to see if L-DOPA affects participants' depressive symptoms, processing speed, and working memory. Our hypothesis is that L-DOPA response, measured as an improvement in gait speed, is associated with a decrease in depressive symptoms and an increase in processing speed and working memory.
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