Clinical Research Directory

Long-term Safety Study of BHV-7000 in Participants With Major Depressive Disorder (MDD)

The purpose of this study is to evaluate the long-term safety and tolerability of BHV-7000, in participants with Major Depressive Disorder (MDD).

A Phase 3 Trial of DT120 for Major Depressive Disorder (Ascend)

A Phase 3 Double-blind, Placebo-controlled Study (Part A) with an Open-label Extension (Part B) Evaluating DT120 Compared to Placebo in Major Depressive Disorder - Ascend

Neuropharmacologic Imaging and Biomarker Assessments of Response to Acute and Repeated-Dosed Ketamine Infusions in Major Depressive Disorder

Background: Most medications that treat depression take weeks or months to work. Researchers want to develop fast-acting treatments. One dose of ketamine has a rapid antidepressant effect. For most people, this lasts a week or less. Repeated doses of ketamine may help maintain this effect. Objective: Main Study: To study the effects of ketamine in treating depression. Ketamine Metabolites Substudy: To study how ketamine effects brain chemistry. To study how ketamine effects the brain. This is done by looking at metabolites, which are created when a drug is broken down. Eligibility: Main Study: People ages 18-65 with major depressive disorder and healthy volunteers Ketamine Metabolites Substudy: Healthy volunteers ages 18-65 Design: Main Study: Participants will be screened in another study, with: * Medical and psychiatric history * Psychiatric and physical exam * Blood, urine, and heart tests Participants will be inpatients at NIH for 4 phases totaling 14-20 weeks. Phase I (2-7 weeks): * Gradually stop current medications * MRI: Participants lie and perform tasks in a machine that takes pictures of the body. * Mood and thinking tests * Blood and urine tests * Sleep test: Monitors on the skin record brain waves, breathing, heart rate, and movement during sleep. * Transcranial magnetic stimulation: A coil on the scalp gives an electrical current that affects brain activity. * Stress tests: Electrodes on the skin measure reactions to loud noises or electric shocks. Phase I tests are repeated in Phases II and III and in the final visit. Phase II (4-5 weeks): * 4 weekly IV infusions of ketamine or a placebo during an MRI or MEG. For the MEG, a cone over the head records brain activity. Phase III (optional): * 8 infusions of ketamine over 4 weeks Phase IV (optional): * Symptoms monitoring for 4 weeks * Participants will have a final visit. They will be offered standard treatment at NIH for up to 2 months. Ketamine Metabolites Substudy: Participants will be screened in another study, with: * Medical and psychiatric history * Psychiatric and physical exam * Blood, urine, and heart tests Participants will be inpatients at NIH for 4 days. Study Procedures: Mood and thinking tests Blood and urine tests 1 infusion of ketamine Spinal tap and spinal catheter: Used to get samples of cerebrospinal fluid (CSF). This is a fluid that moves around and within the brain and spinal cord. Studying CSF will help us learn how ketamine effects brain chemistry ...

A Randomized Study of Azetukalner Versus Placebo in Major Depressive Disorder

X-NOVA2 is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the clinical efficacy, safety, and tolerability of azetukalner as a monotherapy in adult participants diagnosed with Major Depressive Disorder (MDD)

Sensory Synchronized Imaging and Neuromodulation

The purpose of this research study is to better understand the relationship between the type of brain stimulation used and how it changes brain activity in adult military Veterans. The goal is to use this understanding to develop new, personalized brain stimulation. The investigators evaluate brain changes from different types of transcranial magnetic brain stimulation (TMS).

Rapid Antidepressant Dynamics in Acute Neuromodulation Treatments

The goal of this clinical trial is to learn how different types of non-invasive brain stimulation affect mood and brain function in adults with major depressive disorder (MDD). It will also study how brain stimulation may work together with antidepressant treatments. The main questions this study aims to answer are: How do different patterns of brain stimulation affect mood in people with depression? Do brain networks involved in emotion and self-reflection respond differently depending on the type of stimulation? What are the combined effects of brain stimulation and antidepressant treatments on mood and brain activity? Researchers will compare different brain stimulation patterns and target areas to understand their individual and combined effects. Participants will: Receive three types of brain stimulation (intermittent, continuous, and sham) in different sessions Undergo MRI scans during the administration of either a fast-acting or conventional antidepressant. Complete mood assessments during the scan and for one week after each session This study may help identify brain-based strategies to improve treatment for depression. In addition, a subset of participants (\~25) will complete a reward-guided decision-making fMRI task for feasibility purposes.

Cortical rTMS as a Treatment for Depression

Depression is a leading cause of disability worldwide with a 19% lifetime prevalence in the United States. Dysfunctional reward processing is one of the core features of depression. Common treatments of depression include psychological therapies (e.g., cognitive behavioral therapy), medication (e.g., bupropion, sertraline) and psychological therapies and medication combined, but they may not address the function of the reward circuit in depression. These treatments often o not improve depressive symptoms in patients with depression who are classified as having treatment-resistant depression, and they may be unlikely to respond to further medication trials. Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation that enables us to selectively excite or inhibit neural activity. Multiple TMS pulses given consecutively are known as repetitive TMS (rTMS), and the primary clinical location for applying rTMS is the left dorsolateral prefrontal cortex (DLPFC) for treatment of depressive symptoms. Many of these studies have shown that rTMS to the DLPFC may result in decreased depressive symptoms, but is only partially effective (response and remission rates of 41.2 and 35.3%, respectively). This evidence supports the importance of evaluating the efficacy of rTMS in other brain regions, such as the orbitofrontal cortex (OFC), in the treatment of depressive symptoms rather than in the DLPFC.

Multi-site Feasibility of an Integrated Treatment for the Biology and Experience of Depression: The MULTIBED Study

This randomized 2x2 factorial intervention trial administers 8 weekly cognitive behavioral therapy (CBT) sessions (yes/no) and 4 bi-weekly active whole-body hyperthermia (WBH) sessions (yes/no) to adults aged 18 years or older with major depressive disorder (MDD).

An Open-Label Study of Azetukalner in Major Depressive Disorder

X-NOVA-OLE is a multicenter, open-label study to evaluate the long-term safety, tolerability, and efficacy of azetukalner as a monotherapy in adult participants who successfully completed an antecedent Phase 3 study of azetukalner in Major Depressive Disorder (MDD).

Targeting Specific Brain Networks to Treat Specific Symptoms in Depression

Repetitive transcranial magnetic stimulation (rTMS) is a way of non-invasively stimulating specific brain networks and is an established treatment for Major Depressive Disorder (MDD). This proposal will reveal network mechanisms of the therapeutic effects of rTMS by investigating how stimulating each network specifically changes network connectivity and behavior. This will be done in a highly individualized manner in depressed and healthy patients, leading to more effective and more individualized treatments for depression.

Individualized Targeting and Neuromodulation of Late-Life Depression

An open-label, single-arm, clinical research study about how to make transcranial magnetic stimulation (TMS), an FDA-approved treatment, more effective for patients with late-life depression using fMRI.

Xenon Inhalation Therapy for Major Depressive Disorder and Bipolar Disorder

The investigators will test the hypothesis that inhaled xenon will produce a rapid improvement in depressive symptoms in patients suffering from treatment-resistant depression. Specifically, the investigators will conduct a parallel randomized, double-blind crossover study that will compare the effects of xenon-oxygen (35:65 ratio by volume) added to treatment as usual (X-TAU group) to the effects of nitrogen-oxygen (35:65 ratio by volume) added to treatment as usual (N-TAU group). A total of 20 severely depressed patients, 10 with major depressive disorder (MDD) and 10 with Bipolar Depression (BP), will be exposed in random order to N-TAU and X-TAU in a double-blind protocol.

Multimodal MRI Study of Acupuncture's Rapid Antidepressant Mechanisms and Response Prediction in Depression

This study aims to investigate the rapid antidepressant effects of acupuncture and to explore the underlying brain mechanisms using multimodal MRI techniques. In addition, the study will evaluate whether individual treatment responses can be predicted based on neuroimaging and clinical data. Participants diagnosed with mild to moderate depression will be enrolled and will receive acupuncture treatment. Depression-related clinical assessment scales and brain imaging data will be collected before and after treatment. The results of this study may help to better understand the mechanisms of acupuncture in rapid antidepressant treatment and support the development of personalized treatment strategies.

i-CBT and IV Ketamine for Suicidality in Treatment-Resistant Depression: A Randomized, Midazolam-Controlled Clinical Trial

Approximately four thousand Canadians die by suicide every year, and suicide is the second leading cause of death in youth and young adults (15-34 years). Most people with depression experience thoughts of suicide and many will also plan and/or attempt suicide at some time in their life. There is an urgent need for new scalable treatments that can effectively reduce suicidality in people with depression. Cognitive behavioural therapy (CBT) reduces suicidal thoughts and behaviours, and can be delivered through the internet (i-CBT) making it more accessible and scalable. However, i-CBT has not been shown to rapidly reduce suicidal thoughts and behaviours (suicidality), such as within 24 hours. IV ketamine on the other hand has been shown to rapidly reduce thoughts of suicide, but not suicidal behaviours. Therefore, combining i-CBT with IV ketamine may be more effective reducing suicidality than i-CBT treatment with a control treatment. The investigators propose a 13-week, multi-site, study that looks at how combining i-CBT and IV ketamine treatment will affect suicidality in individuals with depression who have recently experienced suicidal thoughts and/or behaviours, but have not responded to previous treatment. All 76 participants will receive a weekly session of i-CBT for 13 weeks, but half will be randomly assigned to also receive six IV ketamine treatments or six IV midazolam treatments (control treatment) over the first initial 30 days. The investigators will measure changes in suicidal thoughts and behaviours before drug treatment and at the primary endpoint (i.e.,day 30), and after 3 months (i.e. Day 91) of the starting treatment.

Natural History of Depression, Bipolar Disorder and Suicide Risk

Mood disorders, such as depression and bipolar disorder, are difficult to treat. One reason is that there are no objective ways to measure how these disorders affect the body and respond to different treatments. In this study, researchers want to perform tests on people undergoing clinical care for mood disorders. The purpose is to understand the experience of receiving treatment for depression, bipolar disorder, and suicide risk. We also hope that this study will help us to predict which medications will improve thoughts of suicide. People 18 years or older who are receiving treatment for depression, bipolar disorder, or suicide risk may take part in this study. Participants must have also been enrolled in protocol 01-M-0254. This study will be conducted at the NIH Clinical Center in Bethesda, MD. The study typically lasts up to 12 weeks, but may last longer if a participant s treatment continues past that time. Participants will have weekly interviews and questionnaires while they are being treated for their mood disorder. Other tests are optional and include psychological testing, blood draws, sleep tests, and imaging scans. These will be done at the start and the end of research participation.

DBS for Depression

The goal of the study is to address the unmet need of TRD patients by identifying brain networks critical for treating depression and to use next generation precision DBS with steering capability to engage these targeted networks. The study's goal will be achieved through 3 specific aims: 1. Demonstrate device capability to selectively and predictably engage distinct brain networks 2. Delineate depression-relevant networks and demonstrate behavioral changes with network-targeted stimulation 3. Demonstrate that chronic DBS using steered, individualized targeting is feasible and safe for reducing depressive symptoms

Predictors of Treatment Outcome in Major Depressive Disorder

Major depressive disorder (MDD) is a common and disabling mental health condition characterized by persistent low mood, loss of interest, and disruptions in sleep, appetite, and daily functioning. Response to treatment varies widely among individuals: while some respond to standard single-drug antidepressant therapy, others require medication combinations or electroconvulsive therapy (ECT). Currently, reliable clinical tools to predict which patients will respond best to specific treatment modalities remain limited. The purpose of this prospective observational study is to identify sociodemographic and clinical factors that predict treatment response and remission at one month in patients diagnosed with MDD. The study specifically investigates whether baseline characteristics, such as age, sex, symptom profiles (including sleep disturbances, appetite changes, and functional impairment), and the presence of psychotic features, are associated with clinical improvement across different treatment approaches. Adult participants aged 18 to 60 receiving psychiatric care at Assiut University Hospital are evaluated upon treatment initiation and followed for one month. Because this is an observational study, all treatment choices, including single antidepressants, combination pharmacotherapy, ECT, or combined regimens, are determined entirely by the treating medical team according to standard clinical practice. Depressive symptom severity and therapeutic response are measured at baseline and after one month using standardized clinical assessments, including the Hamilton Depression Rating Scale (HDRS).

Targeting Large-scale Networks in Depression With Real-time Functional Magnetic Resonance Imaging (fMRI) Neurofeedback

The purpose of this study is to develop a technique called real time fMRI neurofeedback. This technique uses a regular MRI scanner, except that special software allows the researchers to measure activity in participants brain, using fMRI, and then give information, in the form of a feedback signal, which indicates brain activity in real time, while in the MRI scanner. The larger goal of this study is to develop ways to help people, including those with depression, better regulate brain activity. The researchers think that this may be helpful in managing psychiatric symptoms. This study design has three phases, however, only two phases (phase 2 and 3) are considered to be a clinical trial. Phase 2 (part 2) was registered and is NCT05934604. This is the phase 3 (part 3) for this project and is funded by the National Institutes of Health.

Efficacy and Safety of Bupropion Hydrobromide in Adolescents and Children With Major Depressive Disorder

Double-Blind, Placebo-Controlled, Multicenter Study of Efficacy and Safety

Pilot Study of Personalized Aperiodic Transcranial Alternating Current Stimulation in Antenatal Depression (PandA-tACS)

The purpose of this study is to develop the safety, feasibility, and tolerability of a personalized transcranial alternating current stimulation (tACS) approach in antenatal depression.

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

The purpose of this study is to examine the efficacy, safety, and tolerability of CYB003 compared to matching placebo as adjunctive treatment in participants with MDD.

JAK Signaling in Depression

This study will test the hypothesis that Janus kinase (JAK) signaling is involved in major depression (MD) with high inflammation by determining whether its inhibition with baricitinib can improve functional connectivity in reward and motor circuits in association with improved motivation and motor function in MD patients enriched for high C-reactive protein (CRP) and anhedonia.

Phase III Long-term Extension Trial to Assess Safety and Efficacy of CYB003 in MDD (EXTEND)

This is a long- term extension of the double-blind trials APPROACH (CYB003-002) and EMBRACE (CYB003-003). Its aim is to examine the safety and long-term efficacy of CYB003 in participants with MDD.

Study of Lumateperone as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder

This is a multicenter, randomized, double-blind, placebo-controlled parallel-group, fixed-dose study in patients with a primary diagnosis of MDD according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) who have an inadequate response to ongoing ADT.