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.

Depression Studies

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 – 70 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: Jeremy Cohen

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

A Proof of Concept Randomized Controlled Trial of XEN1101 for the Treatment of Major Depressive Disorder

PI: James Murrough, MD, PhD

Study Coordinator: Sara Hameed

Funding: National Institute of Mental Health (NIMH)

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: Patients (18-65 years old) in a current major depressive episode who are currently not taking any antidpressants or are willing to come off their current antidepressant treatment.

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 18 weeks (8 visits)

Compensation: Up to $825 with $250 in travel reimbursement

Clinicaltrials.gov ID: NCT04827901

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

PI: Laurel Morris, PhD

Study Coordinator:Abigail Adams , Grace Butler

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: Grace Butler

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

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

Compensation: Yes

Multidimensional brain connectome features of depression and anxiety

PI: Yael Jacob, PhD

Study Coordinator: Grace Butler

Funding: National Institute of Mental Health

Description: The current study aims to characterize small limbic hippocampus and amygdala subregions structural and functional connectivity in patients with mood and anxiety disorders. We aim to determine the relationship between limbic subregions network features and measures of pathological depression and anxiety.

Inclusion criteria: : Male or female aged 18-55 years who either meet DSM-5 criteria for current major depressive disorder (MDD), Generalized Anxiety Disorder (GAD), OR does not meet for any current or past psychiatric diagnoses.

Exclusion criteria: : Any current or history of schizophrenia or other psychotic disorder, neurodevelopmental disorder, or neurocognitive disorder for patients,active substance use disorder within the past 6 months, or active positive drug screen at MRI assessment

Study Participation Length: Subjects will be in the study for up to 12 weeks. Participation will include 2
visits; 1 screening visit and 1 assessment visit lasting up to 6 hours each.

Compensation: Yes

Network based real-time neurofeedback using ultra-high field MRI to reduce rumination levels in depression

PI: Yael Jacob, PhD

Study Coordinator: Grace Butler

Funding: Friedman Brain Institute (FBI) and Advanced Neuroimaging Research Program (ANRP) Pilot Grant

Description: The current study implements the first real-time fMRI neurofeedback (Rt-fMRI-NF) network-based protocol for up-regulation of the MOFC influence on the precuneus in patients with MDD to reduce rumination levels. This will allow for more accurate explicit brain connections modulation than the standard single brain region activity; creating a larger opportunity for target clinical neuromodulation treatment in individuals with MDD.

Inclusion criteria: Male or female aged 18-65 years who either meet DSM-5 criteria for current major depressive disorder (MDD) OR does not meet for any current or past psychiatric diagnoses.

Exclusion criteria: Any current or history of schizophrenia or other psychotic disorder, neurodevelopmental disorder, or neurocognitive disorder for patients, active substance use disorder within the past 6 months, unstable medical illness, pregnancy, and contraindications to MRI.

Study Participation Length: Subjects will be in the study for up to 12 weeks. Participation will include 5 visits

Compensation: Yes

PTSD Studies

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

Gamified Approach to Maximizing Biobehavioral Inhibition in Trauma-related Conditions (GAMBIT)

PI: Laurel Morris, PhD; Jonathann DePierro, PhD

Study Coordinator: Sydney Starkweather

Funding: National Institute of Health

Description: The purpose of this research study is to pilot a digital cognitive training task toenhance brain plasticity in inhibitory control circuits, called the GAMBIT task. This study will be the first to examine effects of the GAMBIT task onneural flexibility, behavior, and symptoms in participants with PTSD. Understanding whether a patient self-administered task improves flexibility in the neural inhibitory control network is an important step towards developing treatments for PTSD patients, who experience issues related to poor inhibitory control.

Main Inclusion: Male or female aged 18-55 years; Must meet criteria for one of the following study groups: 1. PTSD diagnosis or 2. no lifetime history of any psychiatric disorder

Main Exclusion: Current or lifetime history of schizophrenia or other psychotic disorder, bipolar disorder, obsessive-compulsive disorder (OCD), eating or feeding disorder, neurodevelopmental disorder, or neurocognitive disorder; Substance use disorder within the past 1 year

Study Participation Length: Subjects will participate in the study for up to 80 days (11 weeks; 4 visits)

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: Yolanda (Yolie) Whitaker

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:

Male or female aged 30-65 years
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)
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: $250

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

PI: James Murrough, MD, PhD

Study Coordinator: Yolanda (Yolie) Whitaker

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: Up to $510 for all three visits

Anxiety Studies

Multidimensional brain connectome features of depression and anxiety

PI: Yael Jacob, PhD

Study Coordinator: Grace Butler

Funding: National Institute of Mental Health

Study Participation Length: Subjects will be in the study for up to 12 weeks. Participation will include 2
visits; 1 screening visit and 1 assessment visit lasting up to 6 hours each.

Compensation: Yes

Gamified Approach to Maximizing Biobehavioral Inhibition in Trauma-related Conditions (GAMBIT)

PI: Laurel Morris, PhD; Jonathann DePierro, PhD

Study Coordinator: Sydney Starkweather

Funding: National Institute of Health

Main Inclusion: Male or female aged 18-55 years; Must meet criteria for one of the following study groups: 1. PTSD diagnosis or 2. no lifetime history of any psychiatric disorder

Study Participation Length: Subjects will participate in the study for up to 80 days (11 weeks; 4 visits)

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: Yolanda (Yolie) Whitaker

Funding: National Institute of Health

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

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: Up to $510 for all three visits

Bipolar Disorder Studies

PI: James Murrough, MD, PhD

Study Coordinator: Jeremy Cohen

Funding: LivaNova

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

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

Compensation: Yes

ClinicalTrials.gov ID: NCT03887715

Other Studies

CLINICAL PHARMACOLOGY AND TARGET VALIDATION OF A BIOACTIVE DIETARY POLYPHENOL PREPARATION (BDPP) FOR STRESS-RELATED DISORDERS

PI: James Murrough, MD, PhD

Study Coordinator: Maxine Marchidan

Funding: National Institutes of Health (NIH)/National Center for Commentary and Integrative Health (NCCIH)

Description: The current study will assess the clinical pharmacology of BDPP in healthy subjects treated with three doses of BDPP (low, intermediate and high dose) and evaluate the effect of BDPP on blood levels of inflammatory cytokines, in particular IL-6, at baseline and in response to acute stress.

Inclusion: Participants will be males or females aged 18-55 years, with a body max index (BMI) less than 30.

Exclusion: Any psychiatric diagnosis as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5); substance or alcohol use disorder in the past 2 years; any unstable medical illnesses; any diagnosed inflammatory or autoimmune disorder; clinically significant abnormalities of laboratory tests; use of medication or nutritional supplement known to affect inflammation and polyphenol levels; or female participants who are pregnant or nursing or plan to become pregnant.

Study Participation Length: Subjects will be on study for up to 10 weeks.

Compensation: Yes

A Dose Escalation Study of Harmine in Healthy Subjects

PI: James Murrough, MD, PhD

Study Coordinator: Leah Israel

Funding: Internal Funds

Description: This study is designed to investigate the safety of oral administration of harmine using an open label, two-stage, continual reassessment method with 8 doses of harmine at 100mg, 200mg, 300mg, 500mg, 700mg, 900mg and 1200mg in healthy volunteers. We anticipate that the proposed study will yield the maximum tolerated dose (MTD) for harmine, which will guide future research efforts toward novel diabetes treatments.

Inclusion: Healthy adults; Men and Women, age 21-55; 110-220lbs

Exclusion:

Acute or severe medical illness i.e., delirium, metastatic cancer, decompensated cardiac, liver or kidney failure, major surgery, stroke or myocardial infarction during the three months prior to entry.
Presence of a significant neurological disease such as Parkinson's disease, primary or secondary seizure disorders, intracranial tumors, severe head trauma; neurodegenerative diseases i.e. MS
Presence or history of psychiatric disorder as diagnosed by MINI or SCID

Study Participation Length: Three visits

Compensation: Yes

Cognitive Neuroscience of Mood and Anxiety Disorders

PI: James Murrough, MD, PhD

Study Coordinator: Abigail Adams

Funding: Internal Funds

Description: 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. Understanding the cognitive and neural features of these patients will inform biomarkers that will potentially predict treatment outcome that may lead to more effective, targeted therapies. This will be crucial for reducing the health, social and economic costs of these costly treatments. Our project has the potential to have a major public health impact to advance diagnostic and treatment efficacy for precision medicine for subjects suffering from mood and anxiety disorder

Inclusion: Male or female aged 18-75 years; 1. Meets DSM-V criteria for major depressive disorder (MDD), persistent depressive disorder, other specified depressive disorder, Post Traumatic Stress Disorder, or anxiety disorders (including Generalized Anxiety Disorder, Social
Anxiety Disorder, and Panic Disorder) as determined by the Structured Clinical Interview for DSM-V Axis Disorders (SCID) or the Mini International Neuropsychiatric Interview (MINI) OR 2.Does not meet for any current or past psychiatric diagnoses

Exclusion: Current or history of schizophrenia or other psychotic disorder, neurodevelopmental disorder, or neurocognitive
disorder for patients and for healthy control subjects: any current or lifetime psychiatric disorder ; Active substance use disorder within the past 1 year; Positive urine toxicology screen for drugs of abuse at the time ofscreening*; Any unstable medical illnesses; Women who are pregnant; ; Any contraindications to MRI

Study Participation Length: Includes screening and one scanning visit

Compensation: Yes

Using Digital Technology to Monitor Mood and Anxiety Disorders

PI: Laurel Morris, PhD

Study Coordinator: Abigail Adams

Funding:

Description: We aim to evaluate how smartphone-based assessments of mood, cognitive performance, mobility, sociability, and
physiology compare to gold-standard in-person clinical assessments and clinical symptoms related to mood. By demonstrating the validity
of real-world smartphone-based assessments, we will provide tools that can measure behavioral features that could predict symptom
progression and treatment outcome that may lead to more effective, targeted therapies. This will be crucial for reducing the health, social
and economic costs of costly treatments. Our project has the potential to have a major public health impact to advance diagnostic and
treatment efficacy for precision medicine for subjects suffering from mood and anxiety disorders

Inclusion: Male or female aged 18-75 years; Does not meet for any current or past psychiatric diagnoses as defined by DSM-V criteria as determined by the Structured Clinical Interview for DSM-V Axis Disorders (SCID) or the Mini International Neuropsychiatric Interview (MINI);

Exclusion: Does not speak English ; Does not own a smartphone that can run the study applications (Android or Apple

Study Participation Length: Three visits

Compensation: Yes