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
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
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
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