Clinical Research Directory

PCS in Severe Treatment Resistant Depression

This research study is designed to test if electrical stimulation of the surface of the brain in the frontal region will help treat depressive symptoms. Participants receive intermittent electrical stimulation to the brain, which involves surgically placing electric leads in between the tough fibrous membrane covering the surface of the brain and the surface of the brain itself. This type of stimulation is referred to as bilateral subdural prefrontal cortical stimulation (PCS) because it will specifically target the outer layer of the brain at the midline, right behind the forehead. It uses a pacemaker-like device, the Proclaim Elite SCS System (non-rechargeable) or the Eterna SCS System (rechargeable), both by Abbott Laboratories for stimulation. Although the U.S. Food and Drug Administration (FDA) has approved the Proclaim Elite SCS system for brain stimulation for patients with chronic pain and muscular diseases, such as Parkinson's, its use is still investigational, and the surgery is still experimental for patients who have depression.

Treatment ResistAnt Depression Subcallosal CingulatE Network DBS (TRANSCEND)

The goal of this clinical trial is to evaluate the effectiveness and safety of bilateral stimulation of the subcallosal cingulate white matter (SCCwm) using Deep Brain Stimulation (DBS) as an adjunctive treatment of non-psychotic unipolar Major Depressive Disorder (MDD) in adults.

A Study to Assess Effectiveness and Efficiency of VNS Therapy in Patients With Difficult to Treat Depression.

The primary objective of this study is to assess short, mid and long-term clinical outcomes in patients with difficult to treat depression (such as patients with treatment resistant depression) treated with Vagus Nerve Stimulation (VNS) Therapy as adjunctive therapy.

COpenhagen Magnetic Personalized Accelerated Brain Circuit Therapy for Treatment Resistant Depression

The CoMPACT trial is a randomized double-blinded sham-controlled study aimed at testing a novel accelerated and personalized transcranial Magnetic Stimulation (TMS) treatment for patients with Treatment Resistant Depression (TRD). CoMPACT consists of 25 sessions of intermittent theta-burst transcranial stimulation (iTBS) consisting of high inter-pulse frequency administered five times daily over five consecutive days. The trial will include 78 patients with TRD who will be randomly assigned to one of three groups: * Group 1: Real CoMPACT targeting the left dorsolateral prefrontal cortex (DLPFC). * Group 2: Real CoMPACT targeting a novel site, the left inferior parietal lobule (IPL). * Group 3: Sham CoMPACT targeting the left DLPFC (50%, Group 3a) or left IPL (50%, Group 3b). The hypothesis is that real prefrontal or parietal CoMPACT targeting will significantly alleviate depression symptoms compared to sham targeting, without compromising safety, feasibility, or tolerability. The trial incorporates a personalized approach, using electrical field (E-field) modeling based on individual structural brain scans to tailor and standardize iTBS, ensuring accurate targeting of cortical volume and consistent induced electrical field strength. To delineate the treatment mechanism of action at the brain network level, multi brain mapping models will be implemented. Electroencephalography (EEG) records of spontaneous and TMS-evoked electrical brain activity will be obtained before, during, and after iTBS sessions to understand how the high frequency burst protocol functionally engages the stimulated cortex. Structural and functional brain MRI before and after the treatment will be used to study changes in depression-related brain networks. This will offer key insights into how CoMPACT affects depression-related brain networks and may identify neuroimaging markers for predicting treatment response, and thus informing future TBS treatments for TRD.

Studying the Health of Asians to Advance Knowledge, Treatments, and Interventions for Depression

SHAKTI (from the Sanskrit word for "power") is a 5-year natural history, longitudinal, prospective study of a cohort of 6,000 participants that will help uncover the socio-demographic, lifestyle, clinical, psychological, and neurobiological factors that contribute to antidepressant treatment response (remission, recurrence, relapse and individual outcomes in depressive disorders) and resilience. As this is an exploratory study, we will assess a comprehensive panel of carefully selected participant specific parameters - socio-demographic (age, sex, gender, race, ethnicity, economic); life habits (physical activity, substance use); clinical (medical history, anxious depression, early life trauma), biological (biomarkers in blood, saliva, urine, stool), behavioral (cognitive, emotional), neurophysiological (EEG), and neuroimaging (magnetic resonance imaging; MRI) with the goal of developing the most robust predictive models of depression treatment response and of outcomes.

Dutch-Depression Outcome Trial Comparing 5 Day Multi Daily Neuronavigated Theta Burst Sessions With 6 Weeks rTMS

INTRODUCTION Recent findings from three small studies (total n=59) suggest that three changes in repetitive Transcranial Magnetic Stimulation (rTMS) protocols, called the Stanford Neuromodulation Therapy (SNT) protocol, contribute to extreme high overall remission of 79% in patients with treatment resistant depression (TRD), whereas remission using a standard 10 Hz rTMS protocol is 25%. The improvement using the SNT protocol is achieved by combining 1) accelerated treatment with multiple sessions per day, 2) applying a higher overall pulse dose of stimulation, using intermittent Theta Burst Stimulation (iTBS), and 3) precise targeting of the region in the left dorsolateral prefrontal cortex (DLPFC), using functional MRI guided neuronavigation. OBJECTIVE To determine if the SNT protocol is more (cost-) effective compared to standard 10 Hz rTMS in patients with TRD, even though the number of pulses given in both protocols is equal, i.e., 90,000. STUDY DESIGN Multicenter randomized controlled trial comparing SNT with standard 10Hz rTMS with a follow-up of 25 weeks. STUDY POPULATION 108 Patients with TRD (no response to 2 or more evidence-based treatments). INTERVENTION 50 sessions using the SNT protocol in 5 days. The region of the left DLPFC most anticorrelated with the subgenual anterior cingulate cortex in each participant will be targeted based on subject-specific functional resting state MRI. COMPARISON 30 standard daily 10 Hz rTMS sessions in six weeks, targeting the left DLPFC based on standard measurement procedures of the skull. OUTCOME MEASURES * Remission, based on the Hamilton depression rating scale * Cost effectiveness, based on healthcare resource use * Quality of life and positive mental health * Tolerability and safety * Relapse * Description of opportunities and difficulties with regard to implementation SAMPLE SIZE The investigators will enrol 108 patients (α=0.05, power is 0.80) including adjustment for attrition. COST EFFECTIVENESS ANALYSIS SNT is faster and possibly more effective than 10Hz rTMS leading to a total cost reduction of 22 million each year considering less expensive healthcare, reduced illness duration and absence from work. TIME SCHEDULE Within 36 months, the investigators will recruit and treat 108 patients with TRD: each center will recruit 9 patients per year. After the last follow-up assessments, the investigators will finalise the study within 12 months and report the results.

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.

InTRavenous kEtAmine and immerSive virtUal Reality to Treat dEpression

Depression is a common condition, with serious negative effects on the health and quality of life of those affected. While there are currently various medications which attempt to treat depression, they often take a long time to begin to work and do not work at all for many people. There is therefore a need for new treatments which work quickly and effectively. One such medication is called ketamine. Studies have shown that ketamine can treat symptoms of depression quickly. This quick action sets ketamine apart from many antidepressants that take weeks to show noticeable effects. One way that it may do this is by creating a transient sense or feeling of being separated from reality, such as seeing or hearing things that are not really there. Another way to create these same feelings is with virtual reality (VR), where a person can feel as though they are entering a 3-dimensional virtual computer-generated world by wearing a special headset or goggles with a computer inside. In this study, all participants will receive standard ketamine treatments for depression. Half of the participants will also use a VR headset while receiving the ketamine treatments to see if ketamine and VR acting together provide a better treatment for symptoms of depression than ketamine alone. This is a small pilot trial. The main purpose of this trial is to learn if it is possible to run a larger clinical trial comparing "ketamine and VR" with "ketamine alone", for adults with treatment-resistant depression. The researchers will study this by seeing how many participants take part in the study within 1-2 years, and how many complete the study treatments and tests. The researchers will also compare the two study groups to see if "ketamine and VR" provide a better treatment for symptoms of depression than "ketamine alone".

Deep Brain Stimulation for Treatment Resistant Depression With the Medtronic Activa PC+S

The goal of this study is to use the Activa Primary Cell + Sensing (PC+S) device to study Latent Field Potential (LFP) in the brains of people with Treatment Resistant Depression (TRD) before and during active stimulation. The ultimate goal is to understand the neural network that causes TRD and the changes that DBS cause in that network that results in the antidepressant effects.

Efficacy, Safety, and Tolerability of COMP360 in Participants With TRD

Efficacy, Safety, and Tolerability of a single administration of COMP360 in participants with treatment-resistant depression (TRD)

Efficacy, Safety, and Tolerability of Two Administrations of COMP360 in Participants With TRD

Efficacy, Safety, and Tolerability of two administrations of COMP360 in participants with treatment-resistant depression (TRD)

Psilocybin for Treatment-Resistant Depression in Autism

We propose a first-of-its-kind open-label clinical trial to investigate the feasibility, tolerability, and safety of administering psilocybin in autistic adults with treatment-resistant depression (TRD). In this study, 20 participants (intellectually able and fluent-speech adults) with autism and co-occurring TRD will receive around 20 hours of manualized psychotherapy that has previously been used with psilocybin (Agin-Liebes et al., 2020). They will also receive psilocybin at 2 different time points, firstly a safety dose of 10mg, followed by a treatment dose of 25mg. This study design is in accordance with previous studies investigating the use of psilocybin with psilocybin-assisted therapy (PAT) to treat TRD (Carhart-Harris et al., 2016, 2018)

ipRGC as a Potential Biomarker for Predicting Transcranial Magnetic Stimulation Treatment Response in Major Depressive Disorder

This research explores the potential of retinal ganglion cells (RGCs), particularly intrinsically photosensitive RGCs (ipRGCs), as biomarkers for predicting response to transcranial magnetic stimulation (TMS) in treatment-resistant depression (TRD). We also aim to assess the impact of TMS treatment on RGCs and ipRGCs in TRD patients, investigating associations with clinical improvements and cognitive status. A clinical trial involving 44 patients with treatment-resistant depression (TRD) will be conducted. All participants will receive rTMS targeting the dorsolateral prefrontal cortex (DLPFC). Data will be collected pre- and post-intervention, as well as at a 2-month follow-up, using multiple outcome measures, including the post-illumination pupil response (PIPR). The project seeks to confirm the effectiveness of TMS and the potential of RGCs/ipRGCs as predictors of treatment response, thereby facilitating the development of personalized treatment strategies for TRD patients undergoing rTMS therapy.

Imaging the Effects of Serotonin 2A Receptor Modulation on Synaptic Density in Treatment-resistant Depression (SYNVEST)

Psilocybin, the chemical component of "magic mushrooms", has been administered with psychotherapy in several randomized clinical trials (RCTs) showing large and sustained antidepressant effects. In healthy volunteers, the psychedelic effects of psilocybin have been shown to be blocked by administration of certain medications such as risperidone. The purpose of this study is to use an established SV2A radiotracer produced at our Centre to determine the feasibility of integrating PET imaging in to psilocybin trials. The preliminary imaging data will assess whether psilocybin's antidepressant effects are related to changes in synaptic density in adults with TRD, and whether any changes in synaptic density are associated with psilocybin's actions on the 5-HT2AR.

Treatment With Psilocybin for Chronic Neuropathic Pain and Depression (TRANSCEND)

Psilocybin, the chemical component of "magic mushrooms", has been administered with psychotherapy in several randomized clinical trials (RCTs) showing large and sustained antidepressant effects. The purpose of this study is to assess the feasibility, tolerability, and preliminary efficacy of psilocybin therapy for adults with chronic neuropathic pain and co-morbid treatment resistant depression.

Personalized Therapeutic Neuromodulation for Anhedonic Depression

This study will investigate the anti-anhedonic efficacy of a novel neurostimulation strategy termed accelerated intermittent theta burst stimulation (aiTBS) in participants with treatment resistant depression (TRD).

Accelerated Theta Burst in Treatment-Resistant Depression: A Dose Finding and Biomarker Study

This study evaluates the effectiveness of re-treatment using accelerated schedule of intermittent theta-burst stimulation for treatment-resistant depression. This is an open label study.

Tractography Guided Subcallosal Cingulate Deep Brain Stimulation for Treatment Resistant Depression

Treatment resistant depression remains a major problem for individuals and society. Surgical procedures may provide relief for some of these patients. The most frequently considered surgical approach is deep brain stimulation (DBS) of a part of the brain called the subcallosal cingulate region. However, the effectiveness and safety is not well established. The investigators will use a novel approach using advanced imaging technique (magnetic resonance tractography) to evaluate the feasibility and safety of this surgical approach. An innovative method for the definition of DBS target will be applied that redefines the concept of targeting as one of targeting a symptomatic network rather than a structural brain region using subject-based brain anatomy to define the target location. The correlation between imaging findings at baseline with the mood score changes at different time points of the study will be investigated.

An Open-Label Study to Evaluate the Safety, Tolerability and Pharmacodynamics of BPL-003 in Patients With Treatment Resistant Depression

An open-label, multi-centre, Phase 2a study to evaluate the safety, tolerability, and pharmacodynamics of one and two doses of intranasal BPL-003 combined with psychological support, in patients with treatment resistant depression when administered as monotherapy or as adjunctive therapy with defined SSRIs (citalopram, escitalopram, sertraline or fluoxetine).

Ketamine Associated ACC GABA and Glutamate Change and Depression Remission:

This is a feasibility study and the goal of this project is to evaluate whether peak ACC GABA and glutamate, quantified as a CSF-corrected absolute concentration percent change from baseline, is associated with clinical remission, Montgomery Asberg Depression Rating Scale (MADRS) total score of \<10, to the anti-glutamatergic antidepressant ketamine. As MRS is expensive, we also aim to study a correlation between change in peripheral metabolites (GABA and glutamate) and central GABA and glutamate levels.

Accelerated Intermittent Theta-Burst Stimulation (aiTBS) in Treatment-Resistant Depression of Bipolar II Disorder

The purpose of this study is to investigate the effectiveness of accelerated intermittent theta-burst transcranial magnetic stimulation (aiTBS) in inducing anti-depressant responses in individuals with treatment-resistant depression of bipolar II disorder. This is a double-blind, randomized, sham-controlled trial that targets a single location on the left dorsolateral prefrontal cortex (LDLPFC) using the MagPro rTMS system.

Specialized Pro-resolving Lipid Mediators and Treatment Resistant Depression

The goal of this clinical trial is to determine the impact of omega-3 fatty acids on the production of anti-inflammatory effects and clinical improvement in people with depression who have not responded well to standard antidepressant treatment. The main questions it seeks to answer are: 1. Do omega-3 fatty acids added to ineffective antidepressant treatment increase production of compounds that reduce inflammation? 2. Is the increase in these anti-inflammatory compounds associated with a stronger antidepressant effect? Participants taking antidepressants that have not worked completely will be assigned at random for a 12-week period to one of the following: 1. an omega-3 preparation 2. an inactive placebo During the course of the study, blood tests will be obtained for compounds associated with inflammation, and questionnaires to measure clinical improvement in depressive symptoms will be administered.

A Randomized, Double-Blind Controlled Comparison of NRX-101 vs. Placebo for Adults Being Treated With Robotic Transcranial Magnetic Stimulation for Treatment Resistant Depression: The SPARC-TMS Trial

Major depressive disorder (MDD) is a significant public health problem and leading cause of worldwide disability. Treatment resistance is common in MDD, however, for these individuals, targeted noninvasive brain stimulation is an alternative. Repetitive transcranial magnetic stimulation (rTMS) and more recently, theta-burst stimulation (TBS), are the noninvasive brain stimulation modalities with the largest evidence base in MDD. Although efficacious, an unacceptable proportion of patients do not significantly improve, and several aspects of the TMS parameter space are under investigation to enhance clinical outcomes. DCS has been shown in a randomized trial of more than double the percent response and remission from traditional TMS. When a one day (ONE-D) TMS protocol was combined with DCS, the measured response rate was 87% at one week. This trial will compare response and remission at six weeks following neuronavigated robotic-enabled Transcranial Magnetic Stimulation + NRX-101 (D-cycloserine/lurasidone) vs. TMS+placebo.

DBS for TRD With the Medtronic Percept PC

Of the estimated 30 million Americans who suffer from Major Depressive Disorder, approximately 10% are considered treatment resistant. Deep brain stimulation (DBS) to a region of the brain called the subcallosal cingulate (SCC) is an emerging strategy for treatment resistant depression (TRD), which involves placement of electrodes in a specific region of the brain and stimulating that area with electricity. This is believed to reset the brain network responsible for symptoms and results in a significant antidepressant response. A series of open-label studies have demonstrated sustained, long-term antidepressant effects in 40-60% of patients who received this treatment. A challenge to the effective dissemination of this fledgling treatment is the absence of biomarkers (objective, measureable indications of the state of the body and brain) to guide device placement and select stimulation parameters during follow-up care. By using a DBS device called the Percept PC (Medtronic, Inc) which has the ability to both deliver stimulation to and record electrical signals directly from the brain, this study aims to identify changes in local field potentials (LFPs), specific electrical signals that are thought to represent how the brain communicates information from one region to another, to see how this relates to DBS parameter settings and patient depressive symptomatology. The goal of this study is to study LFPs before and during active DBS stimulation to identify changes that correlate with the antidepressant effects of SCC DBS. The study team will recruit 20 patients with TRD and implant them with the Percept PC system. Participants will be asked to complete short questionnaires and collect LFP data twice daily for the first year of the study, as well as have weekly in person research procedures and assessments with the study team for up to one year. These include meetings with the study psychiatrist, psychologist, symptom ratings, and movement, voice, and video recordings. A brief discontinuation experiment will be conducted after 6 months of stimulation, in which the stimulation will be turned off and patterns of LFP changes will be recorded. The entire study is expected to last about 5 years, parcellated into several study phases. All participants are required to live in the New York metropolitan area for the first several months of the study.