Clinical Research Directory

EEG-Guided Transcranial Magnetic Stimulation for Adults With Depression

The purpose of this research is to see if an experimental treatment for depression called intermittent theta burst stimulation (iTBS), a form of transcranial magnetic stimulation (TMS) can be improved for better results using electroencephalography (EEG) recordings (brain waves) for individuals with Major Depressive Disorder (MDD). This is a feasibility study to test a "closed-loop" procedure which guides the timing of this FDA-cleared form of TMS. Each participant will receive an active experimental treatment, and the timing of the TMS pulses will be at one of three phases in the brain wave of interest.

A Study to Assess the Skin Irritation and Sensitization of Selegiline TDS in Healthy Subjects

The two products used in this study are transdermal patches that contain selegiline. The test drug is the Selegiline Transdermal Delivery System (TDS). The comparator drug is the EMSAM® TDS. The purpose of this research study is to compare how the skin tolerates the test TDS and the comparator TDS. The study will evaluate and compare skin irritation and possible allergic-type skin reactions (sensitization) caused by the two products. The comparison will be based on how the skin responds to repeated applications of each TDS. This includes the assessment of skin irritation during the Induction Period and the evaluation of possible allergic or sensitization reactions after the Challenge Period. In addition, the adhesion of each patch (how well the patch sticks to the skin over time) will be regularly checked, as this is important for both product performance and skin safety.

Mechanisms of Repeated Real-time Biofeedback With 7-Tesla MRI in Depression

Previous work demonstrated that individuals are able to self-regulate their ventral tegmental area (VTA) activity using real-time biofeedback. The current study expands this approach to a larger sample with repeated training sessions to more robustly characterize the effects of VTA modulation. This mechanistic study will assess change in mood and motivation-related measures, as well as neural activity and connectivity changes.

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/

A Study to Evaluate TNX-102 SL Monotherapy Versus Placebo in Participants With Major Depressive Disorder (MDD)

The goal of this clinical trial is to learn if a drug called TNX-102 SL works to treat moderate to severe major depressive disorder in adults. It will also learn about the safety of TNX-102 SL. The main questions it aims to answer are: Does TNX-102 SL improve depression symptoms according to a depression symptom rating scale? What medical problems do participants have when taking TNX-102 SL? Researchers will compare TNX-102 SL to a placebo (a look-alike substance that contains no drug) to see if TNX-102 SL works to treat major depressive disorder. Participants will: Take TNX-102 SL or a placebo every night at bedtime for 6 weeks Visit the clinic once every 2 weeks for checkups and tests

The Research of Ammoxetine Hydrochloride Enteric-coated Tablets in Subjects With Depression

The purpose of this study is to evaluate the efficacy and safety of Ammoxetine hydrochloride enteric-coated tablets in subjects with depression.

Acceptance and Committment Therapy Combined With Ketamine in Difficult-to-Treat Depression.

Ketamine is often used to treat depression where standard treatments have failed. Yet, even with ketamine, depression can persist and make it difficult to keep up with life. This study examines whether it is practical, safe and helpful to use a talk therapy (Acceptance and Commitment Therapy, ACT) in patients with difficult-to-treat depression receiving ketamine through the Ketamine Intervention Program at UBC Hospital. Researchers expect that combining ACT plus Ketamine ("K-ACT") will be feasible, safe, and will help patients functioning better in their daily lives, feeling that they are recovering, and having fewer symptoms of depression.

A Study to Evaluate the Safety and Efficacy of ALKS 7290 as an Adjunctive Therapy to Antidepressants in Adult Participants With Major Depressive Disorder

The purpose of this study is to assess the efficacy, safety and tolerability of ALKS 7290 following oral administration in adult participants with Major Depressive Disorder.

Double-blind, Placebo-controlled Study in Adults With Major Depressive Disorder

This study will evaluate the efficacy and safety of SPN-821 in adults with major depressive disorder

Ketogenic Diet and Neuromodulation in Treatment Resistant Depression

The goal of this clinical trial is to learn if combining a ketogenic diet with a personalized, accelerated brain stimulation treatment (iTBS) works better than iTBS with a standard healthy diet to reduce depression symptoms in adults with treatment-resistant depression. The main questions it aims to answer are: * Does iTBS combined with a ketogenic diet improve depression symptoms more than iTBS combined with a standard healthy diet? * Does the ketogenic diet change ketone levels over time? * Is it safe, tolerable, and feasible to follow a ketogenic diet during accelerated iTBS treatment? We will compare a ketogenic diet to a Canadian Food Guide-aligned diet, both combined with iTBS, measuring depression severity using standard clinician-rated and self-report scales. Participants will: * Follow either a ketogenic diet or a standard healthy diet for 12 weeks, starting with a 3-week lead-in period before iTBS begins * Undergo a course of personalized, imaging-guided accelerated iTBS while continuing their assigned diet * Complete clinical and cognitive assessments, blood tests, and brain MRI scans before and after treatment * Have their ketone levels checked regularly throughout the 12-week period

Implementation of a Multiple Intervention to Promote Healthy Lifestyles in Patients With Depression

This clinical trial aims to investigate whether an integrative approach combining education on the Mediterranean diet and physical activity (PA) can significantly reduce depressive symptomatology in individuals with major depressive disorder. The study will evaluate changes in depressive symptoms and assess biological modulations, including alterations in the gut microbiota and inflammatory markers, resulting from the PA intervention. Participants will be randomized into two arms: the active control group will attend a series of lessons focused on the Mediterranean diet, while the experimental group will participate in the same dietary lessons combined with a structured PA program of 12 weeks.

Sedation and Guided Education for Depression Study

The goal of this clinical trial is to understand how patient education surrounding a one-time, consciousness-altering medical intervention impacts the antidepressant response to the intervention in adults with major depressive disorder. In this study, the consciousness-altering medical intervention is a single infusion of propofol, an intravenous anesthetic. In Part 1 of this study, we aim to answer: Does the focus of patient education influence the antidepressant response to a single intravenous infusion of propofol? In Part 2 of this study, we aim to answer: Does blocking opioid signaling affect the antidepressant response of patient education? Qualifying participants will: * Undergo a single intravenous infusion of propofol which will induce a temporary state of sedation * Wear an EEG cap that records brain activity during sedation * For Part 1: Be randomized to receive either response-focused or diagnosis-focused education about their brain signals after they recover from sedation. * For Part 2: Be randomized to receive a single dose of IV naloxone or IV saline during an educational intervention. * Be asked to fill out surveys about their mood and other measures of well-being throughout the study.

Psilocybin-assisted Therapy for Comorbid Major Depressive Disorder and Alcohol Use Disorder

The goal of this clinical trial is to determine the safety and efficacy of psilocybin assisted Therapy (PAT) in individuals with comorbid Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD). The main question it aims to answer is: \- What is the feasibility and safety of administering PAT in adults with MDD-AUD by evaluating recruitment, retention, tolerability, and safety? Researchers will compare the psilocybin (25 mg) and placebo groups to see if there are any significant differences in frequency of dropouts or serious adverse events. Participants will: * be randomized to receive either psilocybin (25 mg) or placebo * visit the site (in-person and remotely) for a total of 14 times to complete study tasks * receive psilocybin-assisted therapy (PAT) at five various timepoints

Temporal Interference Stimulation in Major Depressive Disorder: A Pilot Feasibility Study

This pilot feasibility study used a randomized, double-blind, within-subject crossover design to explore temporal interference (TI) stimulation in adults with major depressive disorder. Fifteen participants received five weekly 20-minute stimulation sessions in randomized order, including TI stimulation targeting the left dorsolateral prefrontal cortex, left subgenual anterior cingulate cortex, right amygdala, and right ventral striatum, as well as a sham stimulation condition. The primary aim was to establish the feasibility of target-specific TI stimulation and to characterize its effects on functional connectivity and cognitive-emotional processing, assessed by resting-state fMRI and an emotional Stroop task before and after each session. Depressive and anxiety symptoms (HAMD and HAMA) were collected longitudinally across the five-week protocol as a secondary, exploratory measure.

Temporal Interference Transcranial Alternating Current Stimulation for Major Depressive Disorder

This multi-center, double-blind study, randomized controlled trial aims to evaluate the efficacy and safety of Temporal Interference transcranial Alternating Current Stimulation (TI-tACS) in patients with major depressive disorder (MDD) Participants with major depressive disorder will be randomized to receive high-frequency TI-tACS(130 Hz), low-frequency TI-tACS(2Hz), or sham stimulation targeting the right amygdala. The intervention consists of 20 stimulation sessions administered over 2 weeks (twice a day for 5 consecutive days, followed by a 2-day break, and another 5 consecutive days). Clinical assessments will be conducted at baseline, during treatment, and at multiple follow-up time points up to 6 months. The primary outcome for MDD is the change from baseline in the Hamilton Depression Rating Scale (HAMD-17) at week 2. Secondary outcomes include changes in clinical symptoms, cognitive function, and safety profiles.

Evaluation of the Acceptability, Feasibility and Exploration of the Efficacy of an Integrated Care Pathway CARIBOU

Problem statement. Major Depressive Disorder (MDD) is a significant concern among adolescents, characterized by episodes of mood changes, cognitive symptoms, and neurovegetative dysfunction, often lasting months or even years, with a high recurrence rate. In Chile, the prevalence of adolescent MDD is estimated at 8.3%, but only a fraction receive treatment. Post-COVID-19 studies indicate a deterioration in adolescent mental health globally. Treatments for MDD include various psychotherapies, medications like Selective Serotonin Reuptake Inhibitors (SSRIs), and combined approaches, though many adolescents remain untreated or receive non-specific care. Integrated Care Pathways (ICPs), such as the CARIBOU, show promise in providing structured, multidisciplinary care. The CARIBOU model includes components like individual and group Cognitive Behavior Therapy (CBT), caregiver support, and medication algorithms within a Measurement-Based Care (MBC) framework. Pilot studies indicate the feasibility of such interventions, but further research is needed, particularly in resource- limited settings like Chile. Recent initiatives by the Chilean Ministry of Health, underscore the urgency and potential for implementing ICPs like CARIBOU in primary care to address adolescent depression effectively. General Objective: To evaluate the acceptability, feasibility, and explore the efficacy of CARIBOU pathway in treating adolescent depression in primary care. Specific Objectives (SO) 1. To assess the acceptability of the various components of the CARIBOU care model among adolescents, parents/caregivers, and healthcare professionals involved in the treatment of depression in primary care. 2. To assess the feasibility of implementing the different components of the CARIBOU care model for adolescents in the treatment of depression in primary care settings. For example, determine if the research team can recruit a sufficient number of participants at each participating health center within the time of the pilot cluster Randomized Controlled Trial (cRCT) study, evaluate the adherence of healthcare professionals in offering and implementing the proposed interventions, and estimate the participation level of students, parents/caregivers, and healthcare professionals in completing multiple longitudinal outcome assessments to provide sufficient data for a valid analysis. 3. To explore the efficacy of the ICP CARIBOU in reducing depressive symptoms, as measured by the short form of Mood and Feelings Questionnaire (MFQ), compared to treatment as usual (TAU) over 24 weeks. Similarly, determine if the use and implementation of CARIBOU are more effective in reducing anxiety symptoms, measured by the Generalized Anxiety Disorder 7 (GAD-7), and in improving quality of life, measured by the KIDSCREEN-27, family functioning measured by the The McMaster Family Assessment Device - General Functioning Subscale (MFAD-GF), and the overall functionality using the Columbia Impairment Scale, Youth Version (CIS-Y). Methodology. To achieve these objectives, the project will be divided into two phases. I) Formative work: a) the Translation and cultural adaptation of the program of the different components CARIBOU ICP, and b) Youth and family engagement in enhancing the design and relevance of CARIBOU interventions for adolescent depression. And II) The Intervention evaluation phase: a) a Pilot cluster Randomized Controlled Trial study to assess the acceptability and feasibility of implementation CARIBOU ICP in primary care centers and to explore the efficacy of the intervention in reducing depressive and anxiety symptoms and functional impairment and improving quality of life in primary care settings in Chile. This study will involve 72 depressed adolescents and their families randomly allocated to the CARIBOU ICP group (n=36, in two CESFAMs) and to the Treatment As Usual (TAU) (n=36, in two CESFAMs) Expected outcomes. The research project is anticipated to deliver several key outcomes across two phases. In the formative phase, the project will successfully translate and culturally adapt the CARIBOU intervention materials for Chile. This phase will ensure the intervention and assessment tools are culturally relevant and reliable. In the evaluation phase, a pilot cRCT will assess the acceptability and feasibility of implementation of CARIBOU and will explore the intervention's efficacy, aiming to show significant reductions in depression and anxiety symptoms and improvements in overall well-being and social functioning among adolescents. The successful dissemination of findings will inform clinical practices and policymakers, potentially leading to a larger evaluation and dissemination of the CARIBOU intervention in primary care settings, thereby benefiting adolescent mental health in Chile.

A Study to Evaluate the Effectiveness of DT-101 as an Adjunctive Treatment in Patients With Depression

In this study, researchers will learn more about a study drug called DT-101 in participants with Major Depressive Disorder (MDD), a form of depression. The goal of this clinical trial is to learn if DT-101 can treat depression in adults. The effect of DT-101 will be compared to placebo. A placebo looks the drug but contains no medicine. Subjects will attend the clinic for complete general health checks and to complete questionnaires.

Effect of TMS Treatment on Defense Mechanisms and Functionality in Patients With Depression

This prospective observational study aims to evaluate changes in psychological defense mechanisms in patients with non-psychotic major depressive disorder (MDD) undergoing repetitive Transcranial Magnetic Stimulation (rTMS) therapy. The study investigates whether rTMS induces a shift from immature to more mature defense mechanisms and assesses how these changes relate to improvements in depressive symptom severity, anxiety levels, and overall functionality at baseline, 1-month, and 3-month follow-ups.

Prescribing the Right Agent for Depression in Adults

Depression is a common mental health problem affecting almost 300 million people worldwide. Antidepressants are recommended as one of the first line treatments for people with moderate-to-severe symptoms of depression. In our recent trial, PETRUSHKA, on the acute treatment of depression, we demonstrated that the PETRUSHKA Tool, an evidence-based shared decision support system to personalise antidepressant treatment, in comparison with usual care reduced by almost 40% the number of participants stopping their antidepressant early, also improving their depression and anxiety symptoms. To identify the best treatment for each individual, the PETRUSHKA Tool used clinical and demographic predictors. Pilot data show that genetic information can aid stratification of people experiencing depression and better target their treatment. Genetic data can be collected using low-cost DNA-sequencing technology in diverse clinical settings and low-resource environments. Hence, we hypothesised that individual-level pharmacogenomic information can further personalise antidepressant treatment. In this project called PRADA ("Prescribing the Right Agent for Depression in Adults"), we will develop and test in a global trial across Ethiopia, Pakistan and the UK, an evidence-based multimodal web-tool to help participants and clinicians choose the best pharmacological treatment for depression jointly, based on participant preferences and their individual clinical, demographic, cultural, and also genetic profile (PRADA Tool). We will compare the new tool with the PETRUSHKA Tool in a blind fashion, measuring adherence to antidepressant treatment, clinical response and quality of life over a 12-month follow-up.

A Study to Evaluate the Effectiveness of DT-101 in Patients With Depression

The goal of this clinical trial is to learn if DT-101 can treat depression in adults. The effect of DT-101 will be compared to placebo. Subjects will attend the clinic every couple of weeks complete general health checks and complete questionnaires.

Pilot Study: Establishing Glutamatergic Changes in Rapid Antidepressant Effects of Ketamine

In the treatment of Major Depressive Disorder (MDD), ketamine can produce rapid but short-lasting improvements in mood. In order to develop a new generation of treatments with rapid and sustained efficacy, a better understanding of the mechanism of action is urgently needed. One candidate mechanism is the modulation of synaptic strength mediated by glutamatergic activity as ketamine has been suggested to increase synaptic strength. Although determining how ketamine impacts the glutamatergic system is essential to isolating its mechanism of action, the invasive nature of most assessment methods has limited our ability to do so in humans. The proposed research aims to determine if changes in glutamatergic activity, reflecting the modulation of synaptic strength, underlie the antidepressant effects of ketamine. In this project, the investigators will utilize a novel measure of glutamate imaging, GluCEST, to assess changes in glutamatergic activity to assess synaptic strength following ketamine administration. Ten individuals (aged 25-65) with a DSM-V diagnosis of MDD will undergo baseline GluCEST imaging prior to and following ketamine infusion. Both clinician-administered and subjective mood measures will be collected. It is predicted that ketamine will improve mood and increase glutamatergic activity and synaptic strength. Results from this project have the potential to identify the modifiable mechanisms by which rapid antidepressants work which could ultimately stimulate the development of novel interventions that work through the modulation of glutamatergic activity.

An Open-Label Extension Study to Evaluate the Safety and Tolerability of SPT-300 (GlyphAllo) in Participants With Major Depressive Disorder, With or Without Anxious Distress (BUOY-1 OLE Study)

This is an open-label, monotherapy, extension study to evaluate the safety and tolerability of SPT-300 (GlyphAllo) in adults with major depressive disorder (MDD), with or without anxious distress.

A Study to Evaluate the Efficacy and Safety of SPT-300 (GlyphAllo) in Participants With Major Depressive Disorder, With or Without Anxious Distress (BUOY-1 Study)

This is a randomized, parallel-group, double-blind, placebo-controlled, monotherapy study to evaluate the efficacy, safety, and tolerability of SPT-300 (GlyphAllo) in adults with major depressive disorder (MDD), with or without anxious distress.

Physical Activity-based Intervention in Depressed Patients: Clinical, Neurophysiological, Epigenetic and Metabolic Correlates

The goal of this clinical trial is to investigate the effect of a structured physical activity (PA) program on depressive symptomatology in adults with a diagnosis of major depression disorder (MDD). The study will evaluate changes in depressive symptoms and assess neurophysiological and biological modulations, including epigenetic, transcriptomic, and metabolic changes resulting from the PA intervention. The main questions it aims to answer are: * Does physical activity have an impact on depressive symptoms in patients affected by depression? * What are the neurophysiological, epigenetic, and metabolic mechanisms through which PA can modulate the intensity of depressive symptoms? Participants will be randomized into two arms: the intervention group (n total=55), in treatment with antidepressants, participating in a 12-weeks PA program; the control group (n total=55), patients in treatment with antidepressants, without receiving the PA program. All participants will be assessed at three-time points: T0 (baseline, before initiating the trial), T3 (after three months; at the end of the 12-week PA program), and T6 (6th-month follow up; three months after the PA completion). At each assessment, all participants will: * Complete clinical evaluation questionnaires * Provide blood samples * Undergo electroencephalogram (EEG) measurements. * Wear an actigraph 24 hours a day for 7 days before the initiation of the trial, at T3, and at T6.