Ongoing Studies

We are heavily involved in research on depression, post-traumatic stress disorder, and other mood and anxiety conditions. While we focus many of our current studies on novel therapeutics, we also design studies to help us understand the development, progression, and/or course of a given illness. We cannot always offer you a specific treatment, but we hope that your participation in our research might at least inform our understanding of the nature of mood and anxiety disorders. As participants, you make critical contributions to our ability to understand how mood and anxiety disorders work. We know many people come to us hoping to feel better; we do our best to help those who do. Even if we can’t offer you treatment, we hope you will seriously consider participating in one of our studies. Your participation may make it possible for us to help someone with a condition much like yours in the future.

Below is a list of our currently active studies, organized by treatment area or problem.

Electrophysiological Biomarkers to Optimize Deep Brain Stimulation for Depression

PI: Helen Mayberg, MD 

Screening Coordinator: Emma Meyer

Funding: National Institutes of Health

Description: Deep brain stimulation (DBS) to the subcallosal cingulate region, also called brain Area 25 or the SCC, is an experimental treatment strategy for treatment-resistant depression (TRD). This surgical procedure involves the imaging guided placement of electrodes in a specific region of the brain and stimulating that area continuously with an implanted pulse generator. This is believed to reset the brain network responsible for depressive symptoms, resulting in sustained antidepressant response over time. The goal of this project is to refine and optimize this treatment approach using a newly available neuromodulation system (the Medtronic Summit RC+S) that allows brain activity during ongoing therapeutic DBS to be recorded from the brain in real-time. Also, this study will further define brain readouts that track depression recovery, providing novel strategies to monitor and guide treatment and device programming decisions in patients receiving DBS for TRD. The Nash Family Center for Advanced Circuit Therapeutics has more information on DBS research, and the Center for Neuromodulation at Mount Sinai West has more information on DBS surgery.

Inclusion: Individuals aged 25-70 years who currently meet criteria for major depressive disorder (unipolar depression) and who do not have other significant psychiatric diagnoses. Participants need to be currently depressed with a current duration of two years or more and have failed to respond to a minimum of 4 different treatments (3 different medications, psychotherapy, ECT) in the current episode.       

Exclusion: Individuals with current neurological disease, unstable medical condition, active suicidal ideation, history of a suicide attempt in the last 6 months, and those unable to undergo a MRI will not be permitted to participate.

Study Participation Length: Participants will be asked to complete short questionnaires and collect brain activity data twice a day from home, as well as have weekly in person research visits, for one year at The Center for Advanced Circuit Therapeutics at Mount Sinai West. These include meetings with the study psychiatrist and psychologist, assessments, and symptom ratings, with periodic EEGs (scalp brainwave recordings) and brain scans to measure metabolic activity (PET scans).  A brief discontinuation experiment will be conducted after 6 months of active stimulation, in which the device will be turned off and patterns of LFP changes will be recorded. Long-term participant monitoring will continue with ongoing scheduled intermittent assessments every 6 months or as needed for up to 10 years. All participants are required to live in the New York metropolitan area for the first two years of the study.

 

PCORI ELEKT-D: ECT vs Ketamine Trial

PI: James Murrough, MD, PhD   

Study Coordinator: Audrey Evers

Funding: Patient Centered Outcomes Research Institute (PCORI)

Description: This is a multi-site randomized trial of electroconvulsive therapy (ECT) versus Ketamine for patients with treatment resistant depression (TRD). Patients will be randomized to receive ECT 3 times per week or ketamine 2 times per week over the course of 3-5 weeks.

Main Inclusion: Primary MDD (unipolar) diagnosis, at least 2 trials of antidepressants and/or augmentation strategies, willing to receive either ECT or ketamine, medically healthy, between ages 21-75

Main Exclusion: Bipolar Disorders, psychotic symptoms in the current episode, diagnosis of a psychotic disorder

Study Participation Length: acute phase 4 weeks, follow up 6 months

Compensation: Yes

Clinicaltrials.gov ID: NCT03113968 

 

An Experimental Therapeutics Study of Ixekizumab, a Monoclonal Antibody Against Interleukin 17A, on Anhedonia, Reward Circuit Function, and Blood Brain Barrier Physiology in Patients with Treatment- Resistant Depression

PI:  James Murrough, MD, PhD  

Study Coordinator: Mirabel Sleiman, Sara Hameed

Funding: Hope for Depression Research Foundation

Description: The primary objective of the current study is to test the antidepressant effect of ixekizumab as compared to placebo in patients with TRD. Participants will be randomized to receive either  (1) ixekizumab 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2 and 4, or (2) matching placebo injections. Participants will be asked to complete 5 in-person visits, which will also include pre and post treatment brain imaging, blood draws, physical exams and clinical assessments to evaluate symptoms of depression and anhedonia (inability to experience pleasure).

Inclusion: 18 – 65 years old, Patients in a current major depressive episode who have not responded to two antidepressant treatments in their current episode

Exclusion: Lifetime history of psychotic features, diagnosis of schizophrenia, diagnosis of bipolar disorder, MRI contraindications (e.g. metal in the body)

Study Participation Length: Up to 12 weeks (5 visits)

Compensation: Yes

 

RECOVER: A PRospective, Multi-cEnter, Randomized Controlled, Blinded Trial DemOnstrating the Safety and Effectiveness of VNS Therapy® System as AdjunctivE Therapy Versus a No Stimulation Control in Subjects With Treatment-Resistant Depression.

PI: James Murrough, MD, PhD

Study Coordinator: Emma Meyer

Funding: LivaNova

Description: The purpose of this study is to assess and estimate the long-term effectiveness and safety of Vagal Nerve Stimulation in subjects with treatment resistant depression (TRD). Patients will be randomized prior to implantation to receive active treatment or a no stimulation control. After implantation, patients will have two weeks of recovery prior to returning to the research site to begin the double blinded phase. All patients will then continue to be followed for approximately 4 years of open label study participation.

Inclusion: 18 or older, unipolar or bipolar depression, with documented evidence of inadequate response to at least four trials of antidepressant treatments including ECT

Exclusion: Any history (current and/or lifetime) of one or more schizophrenia-spectrum or other psychotic disorders including: schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, and major depressive disorder with psychosis (unipolar or bipolar), and/or psychotic depression (unipolar or bipolar) based on the MINI (does not include psychosis occurring in the context of a manic episode of a subject with bipolar disorder). An active primary diagnosis of one or more of the following disorders: obsessive-compulsive disorder, eating disorder, or post-traumatic stress disorder based on the MINI.

Study Participation Length: Up to 5 years (1 year of active research, 4 years of continued follow-up)

Compensation: Yes

ClinicalTrials.gov ID: NCT03887715

 

Tianeptine for Treatment-Resistant Depression (TRD)

PI: James Murrough, MD, PhD

Study Coordinator: Amelia Karim

Funding: Hope for Depression Research Foundation

Description: The current study aims to assess the effectiveness of Tianeptine in TRD patients, to examine neural responses to social rejection and acceptance and thermal pain in MDD patients, and to identify a physiologic/behavioral signature indicative of opioid deficiency that predicts response to tianeptine. The study involves two MRI scans with 8 weeks of treatment with Tianeptine treatment.

Inclusion Criteria: Male or female from 21-50 years old with diagnosis of treatment resistant depression, at least 2 trials of antidepressants and/or augmentation strategies.

Exclusion Criteria: Drug or alcohol abuse, Past or current psychosis, psychotic disorder (including psychotic MDD), mania, or bipolar disorder. Failed depression treatment with electroconvulsive therapy, intravenous ketamine or esketamine. Having contraindication to MRI scanning (such as metal in body) or inability to tolerate the scanning procedures (e.g., severe obesity, claustrophobia)

Study Participation Length: Up to 10 weeks (10 visits)

Compensation: Yes

Clinicaltrials.gov ID: NCT04249596

 

Real-time biofeedback with 7-Tesla MRI for neurocircuit based treatment of depression

PI: Laurel Morris, PhD

Study Coordinator: Maxine Marchidan

Funding: Brain and Behavior Research Fund

Description: The purpose of this study is to investigate whether brain-computer interface (BCI) technology can help improve depression symptoms. Participants will undergo an fMRI brain scan during which they will train to use certain thoughts to increase activity within a specific area of the brain.

Inclusion: 18 – 45 years old, Patients in a current major depressive episode

Exclusion: Lifetime history of psychotic features, diagnosis of schizophrenia, diagnosis of bipolar disorder, MRI contraindications (e.g. metal in the body), Individuals currently taking antidepressant medication

Study Participation Length: Up to 5 weeks

Compensation: Yes

Clinicaltrials.gov ID: NCT04138680

 

Characterizing constructs of motivation and the midbrain dopaminergic system in depression with ultra-high field MRI

PI: Laurel Morris, PhD

Study Coordinator: Maxine Marchidan

Funding: National Institute of Mental Health

Description: The purpose of this research study to investigate motivation in people with depression compared to control subjects and to asses how motivation relates to the structure and function of a brain region called the ventral tegmental area. Participants will be asked to complete 2 to 3 in-person visits, each lasting roughly 4 hours. During these appointments, participants will complete interviews and clinical self-report scales to evaluate symptoms of depression, motivation, and anhedonia (inability to experience pleasure), as well as computerized cognitive tasks. One of the visits will also involve an MRI scan lasting no more than 2 hours.

Inclusion: 18 – 45 years old, Patients in a current major depressive episode

Exclusion: Lifetime history of psychotic features, diagnosis of schizophrenia, diagnosis of bipolar disorder, MRI contraindications (e.g. metal in the body), Individuals currently taking antidepressant medication

Study Participation Length: Up to 4 weeks (2-3 visits)

Compensation: Yes

 

Neuro-Immune Biotypes of Depression: Towards Pathophysiology-Based Diagnosis and Personalized Treatment

PI:  James Murrough, MD, PhD   

Study Coordinator: Emma Meyer

Funding: Charles A. Dana Foundation

Description: The current study aims to integrate advanced assessments of the brain, the immune system and of clinical symptoms in patients with major depressive disorder (MDD) in order to ultimately understand whether there are unique subgroups of MDD. Other recent studies suggest that stress impacts the blood-brain barrier (BBB), which is a protective barrier between the brain and the blood. BBB damage caused by stress might allow certain immune system proteins to enter the brain that wouldn't normally. This infiltration might alter brain activity and may lead to MDD. This study will use advanced brain imaging techniques at the 7T level (magnetic resonance imaging, MRI) to understand the relationships between BBB damage, the immune system and brain function in MDD and healthy non-depressed volunteers. If successful, the proposed project will advance our understanding of MDD and may point out specific sub-groups of MDD that may benefit from more specific treatments.

Inclusion criteria: Male or female from 18-55 years who meet DSM-V criteria unipolar major depressive disorder OR Healthy Volunteers who do not meet for any current or past psychiatric diagnoses as defined by DSM-V criteria;       

Exclusion criteria: Diagnosis psychotic disorder, neurodevelopmental disorder, or neurocognitive disorder, current use of any psychiatric medication, any diagnosed inflammatory or autoimmune disorder, any contraindications to MRI

Study Participation Length: Up to 4 weeks (2-3 visits)

Compensation: Yes

 

Cognitive Neuroscience of Mood and Anxiety Disorders

PI: James Murrough, MD, PhD

Study Coordinator: Emma Meyer

Funding: Internal

Description: The current study acts as an umbrella protocol utilizing neuroimaging and cognitive tasks to investigate the various effects of mood and anxiety disorders in adults. We aim to conduct a set of cognitive and clinical assessments, and high-resolution MRI-based neural measurements in subjects with mood and anxiety disorders, with the aim of fully phenotyping these individuals.

Inclusion: Male or female from 18-75 years who meet DSM-V criteria unipolar major depressive disorder who do not meet for any current or past psychiatric diagnoses as defined by the Structured Clinical Interview for DSM-V Axis Disorders (SCID) or the Mini International Neuropsychiatric Interview (MINI)

Exclusion: Current or history of bipolar disorder, schizophrenia or other psychotic disorder, neurodevelopmental disorder, or neurocognitive disorder for patients and for healthy control subjects: any current or lifetime psychiatric disorder as determined by the Structured Clinical Interview for DSM-V Axis Disorders (SCID) or the Mini International Neuropsychiatric Interview (MINI)

Study Participation Length: Up to 4 weeks (2-3 visits)

Compensation: Yes

Adding Trauma-focused Psychotherapy to Ketamine Treatment for Chronic PTSD: A Pilot Study

PI: Adriana Feder, MD

Study Coordinator: Oneysha Brown

Funding: Internal

Description: This is an open-label pilot study, which aims to see if the addition of Written Exposure Therapy (WET) to a course of ketamine infusions can help mitigate posttraumatic stress disorder (PTSD) symptoms in individuals with chronic PTSD. In a previous study, we found that a course of six (6) infusions of ketamine led to a greater reduction in PTSD symptoms compared to the psychoactive placebo control midazolam. The results of this study could help develop novel combined treatments for PTSD.

Main Inclusion: Primary chronic PTSD diagnosis, between 18-70 years old

Main exclusion: Lifetime history of psychosis, drug or alcohol use disorder within the past 3 months, any contraindications to ketamine infusions, currently receiving an evidence-based, trauma-focused therapy

Study Participation Length: Participation could last as long as 27 weeks.

Compensation for all study visits: Yes

 

Stress and Atherosclerotic Plaque Macrophages: A Systems Biology Approach – PET/MRI of the Brain-Hematopoiesis-Atherosclerosis Axis in PTSD Patients

PI: Zahi Fayad, PhD and James Murrough, MD, PhD

Study Coordinator: Sarah Rutter

Funding: National Institute of Health

Description: This is a two-center five-year prospective observational study examining the effect of PTSD on vascular inflammation, proliferation, and plaque burden. The study centers will be TMII at Mount Sinai and the Athinoula A. Martinos Center for Biomedical Imaging at MGH. This Project will include two study visits: one screening visit and one imaging visit, to be completed in two different days and within 4 weeks apart.

Three groups of individuals will be recruited:

  • Group 1 includes diagnosed PTSD subjects from at least 1 year prior to enrollment
  • Group 2 (trauma control group) includes control subjects who have been exposed to trauma without developing PTSD symptoms from at least 1 year prior to enrollment
  • Group 3 (healthy control group) individuals who have neither PTSD nor exposure to trauma

Main Inclusion:

  1. Male or female aged 30-65 years
  2. Does not meet for any current or past psychiatric diagnoses as defined by DSM-V criteria (Healthy Control)OR Meets DSM-V criteria for PTSD from at least 1 year prior to enrollment (PTSD) OR meets DSM-V criteria A of PTSD without satisfying criteria for a PTSD diagnoses according to the DSM-V from at least 1 year prior to enrollment (Trauma Control)
  3. Have a level of understanding of the English language sufficient to agree to all tests and examinations required by the study and must be able to participate fully in the informed consent process

Main Exclusion: Clinical history of atherosclerotic disease (prior myocardial infarction, stroke, peripheral artery disease) or any contraindications to MRI, including claustrophobia, any trauma or surgery which may have left magnetic material in the body, magnetic implants or pacemakers, and inability to lie still for 1 hour or more.

Study Participation Length: 2 Visits

Compensation: Yes    

 

Transdiagnostic Multimodal 7 Tesla MRI of the Locus Coeruleus in Human Pathological Anxiety

PI: James Murrough, MD, PhD

Study Coordinator: Sarah Rutter

Funding: National Institute of Health

Description: The purpose of this research study is investigate the brain processes underlying anxiety disorders. In this particular study, we aim to further our understanding about a part of the brain called the locus coeruleus (LC) by running the first high-resolution 7-Tesla (7T) MRI study of this structure in patients with anxiety. The LC is important to study because it plays a big role in the brains response to stressful situations. If successful, this study will provide the first study of the human LC system in patients with anxiety. We anticipate this work will help to diagnose anxiety disorders and provide new routes for treatments.

Main Inclusion: Primary chronic PTSD diagnosis, between 18-65 years old

Main Exclusion: Lifetime history of psychotic features, diagnosis of schizophrenia, diagnosis of bipolar disorder, any clinically significant axis II disorder, drug or alcohol abuse/dependence within preceding year, serious unstable medical illnesses, ) or any contraindications to MRI, including claustrophobia

Study Participation Length: 1-3 study visits with each visit lasting 3-7 hours. If the study is completed in 2 or 3 visits, these visits will need to be within 1 month of each other.

Compensation for all study visits: Yes

Transdiagnostic Multimodal 7 Tesla MRI of the Locus Coeruleus in Human Pathological Anxiety

PI: James Murrough, MD, PhD

Study Coordinator: Sarah Rutter

Funding: National Institute of Health

Description: The purpose of this research study is investigate the brain processes underlying anxiety disorders. In this particular study, we aim to further our understanding about a part of the brain called the locus coeruleus (LC) by running the first high-resolution 7-Tesla (7T) MRI study of this structure in patients with anxiety. The LC is important to study because it plays a big role in the brains response to stressful situations. If successful, this study will provide the first study of the human LC system in patients with anxiety. We anticipate this work will help to diagnose anxiety disorders and provide new routes for treatments.

Main Inclusion: Primary chronic PTSD diagnosis, between 18-65 years old

Main Exclusion: Lifetime history of psychotic features, diagnosis of schizophrenia, diagnosis of bipolar disorder, any clinically significant axis II disorder, drug or alcohol abuse/dependence within preceding year, serious unstable medical illnesses, ) or any contraindications to MRI, including claustrophobia

Study Participation Length: 1-3 study visits with each visit lasting 3-7 hours. If the study is completed in 2 or 3 visits, these visits will need to be within 1 month of each other.

Compensation for all study visits: Yes

RECOVER: A PRospective, Multi-cEnter, Randomized Controlled, Blinded Trial DemOnstrating the Safety and Effectiveness of VNS Therapy® System as AdjunctivE Therapy Versus a No Stimulation Control in Subjects With Treatment-Resistant Depression.

PI: James Murrough, MD, PhD

Study Coordinator: Emma Meyer

Funding: LivaNova

Description: The purpose of this study is to assess and estimate the long-term effectiveness and safety of Vagal Nerve Stimulation in subjects with treatment resistant depression (TRD). Patients will be randomized prior to implantation to receive active treatment or a no stimulation control. After implantation, patients will have two weeks of recovery prior to returning to the research site to begin the double blinded phase. All patients will then continue to be followed for approximately 4 years of open label study participation.

Inclusion: 18 or older, unipolar or bipolar depression, with documented evidence of inadequate response to at least four trials of antidepressant treatments including ECT

Exclusion: Any history (current and/or lifetime) of one or more schizophrenia-spectrum or other psychotic disorders including: schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, and major depressive disorder with psychosis (unipolar or bipolar), and/or psychotic depression (unipolar or bipolar) based on the MINI (does not include psychosis occurring in the context of a manic episode of a subject with bipolar disorder). An active primary diagnosis of one or more of the following disorders: obsessive-compulsive disorder, eating disorder, or post-traumatic stress disorder based on the MINI.

Study Participation Length: Up to 5 years (1 year of active research, 4 years of continued follow-up)

Compensation: Yes

ClinicalTrials.gov ID: NCT03887715