New York, New York 10032

  • Treatment Resistant Depression

Purpose:

The study will be conducted in parallel at two sites: the Clinic for Aging, Anxiety and Mood Disorders (CAAM) at Columbia University/New York State Psychiatric Institute (CU/NYSPI) and the Mood and Anxiety Disorders Program at the Icahn School of Medicine at Mount Sinai (MSSM). The following procedures will be approved by the local Institutional Review Boards (IRBs) at each site, where the site PIs (Bret Rutherford, MD at CU/NYSPI and James Murrough, MD at MSSM) will be responsible for overseeing conduct of the study at their respective site. Dr. Jonathan Javitch is the scientific leader of this program and holds the IND for tianeptine use in this study. Investigators will recruit 75 participants with current unipolar MDD, non-delusional, between 21-50, who have failed at least 2 two adequate treatment trials with a standard antidepressant. Participants with only 1 previous adequate treatment trial may receive their second trial at CU/NYSPI before continuing on to main study protocol. Patients will receive an 8-week treatment trial of tianeptine. Patients will also undergo structural and task-based magnetic resonance imaging (MRI) that will be performed under Dr. Rutherford's direction at CU/NYSPI in order to maintain the internal validity of the data set. Approval has been granted for use of the MRI facility for this study by the Director of MRI Research at the New York State Psychiatric Institute. CU/NYSPI and MSSM subjects will be transported to CU/NYSPI to complete neuroimaging procedures as described below. Participants will be screened for MRI clearance during their screening visit and again at CU/NYSPI on the day of the scan. Subjects will be asked MRI screening questions to ensure that are scanning eligible. Participants will also have additional tubes of blood drawn for human whole-genomic testing. This microarray will be used to identify regions of the human genome that contribute to disease susceptibility and phenotypes. The Illumina human whole-genome array will be used to provide a comprehensive view of the genome, detects single nucleotide polymorphisms and other variations across the genome.


Study summary:

Major depressive disorder (MDD) is a leading cause of disability in adults worldwide (~16M patients in United States alone). Unfortunately, only 35-40% of patients achieve full remission following first-line treatment and treatment-resistant depression (TRD), failure to respond to 2 or more treatments, is a critical clinical problem. As with MDD, there is mechanistic heterogeneity in TRD and consequently, there is a need to develop treatments targeted to biologically distinct subgroups of patients. Significant evidence suggests dysfunction of endogenous opioid signaling pathways as a key biological deficit in some MDD patients. Investigators hypothesize that a subgroup of MDD patients with deficient opioid receptor signaling who have failed previous trials of antidepressants will better respond to pharmacological interventions specifically targeting this biological mechanism. In this application, Investigators propose to target the mu-opioid receptor (MOR) in TRD patients by using the antidepressant tianeptine. Although not available in the United States, Tianeptine is an atypical antidepressant that has been used clinically in Europe, Asia, and South America since the late 1980s in millions of patients. Until recently tianeptine's molecular mechanism of action had remained unknown. Tianeptine is a different type of antidepressant than those currently approved in the United States in that it has a different mechanism of action than other antidepressants. Tianeptine is an opioid antagonist; it binds at the mu-opioid receptor. Currently approved antidepressants act on other systems of the brain that primarily affect serotonin, norepinephrine, and dopamine. Work in our laboratories has shown that tianeptine acts as a selective agonist of MOR, signaling in a manner analogous to enkephalins and endorphins, the endogenous opioid peptides. The investigator applied for and received an IND to import and use tianeptine for this study. The study will be conducted in parallel at two sites: the Clinic for Aging, Anxiety and Mood Disorders (CAAM) at Columbia University/New York State Psychiatric Institute (CU/NYSPI) and the Mood and Anxiety Disorders Program at the Icahn School of Medicine at Mount Sinai (MSSM). The following procedures will be approved by the local Institutional Review Boards (IRBs) at each site, where the site PIs (Bret Rutherford, MD at CU/NYSPI and James Murrough, MD at MSSM) will be responsible for overseeing conduct of the study at their respective site. Dr. Jonathan Javitch is the scientific leader of this program and holds the IND for tianeptine use in this study. Investigators will recruit 75 participants with current unipolar MDD, non-delusional, between 21-50, who have failed at least 2 two adequate treatment trials with a standard antidepressant. Participants with only 1 previous adequate treatment trial may receive their second trial at CU/NYSPI before continuing on to main study protocol. Patients will receive an 8-week treatment trial of tianeptine. Patients will also undergo structural and task-based magnetic resonance imaging (MRI) that will be performed under Dr. Rutherford's direction at CU/NYSPI in order to maintain the internal validity of the data set. Approval has been granted for use of the MRI facility for this study by the Director of MRI Research at the New York State Psychiatric Institute. CU/NYSPI and MSSM subjects will be transported to CU/NYSPI to complete neuroimaging procedures as described below. Participants will be screened for MRI clearance during their screening visit and again at CU/NYSPI on the day of the scan. Subjects will be asked MRI screening questions to ensure that are scanning eligible. Participants will also have additional tubes of blood drawn for human whole-genomic testing. This microarray will be used to identify regions of the human genome that contribute to disease susceptibility and phenotypes. The Illumina human whole-genome array will be used to provide a comprehensive view of the genome, detects single nucleotide polymorphisms and other variations across the genome. The major goals of this project are (1) to determine if tianeptine is an effective antidepressant in patients who have failed two previous trials, (2) to define the relationship between opioid signaling deficits and response to tianeptine treatment, and (3) to develop a comprehensive assessment battery capable of identifying endogenous opioid signaling deficits to explore biological heterogeneity in the TRD population.


Criteria:

Inclusion Criteria: 1. Age 21-50 years, male or female 2. Current diagnosis of Unipolar Major Depressive Disorder (MDD) without psychotic features 3. 24-item Hamilton Rating Scale for Depression (HRSD) ≥ 16 4. At least two previous antidepressant treatment failures (adequate trial within current episode) with an SSRI, SNRI, bupropion, tricyclic antidepressant, mirtazapine, nefazodone, monoamine oxidase inhibitor, or transcranial magnetic stimulation (TMS) 5. Capable of providing informed consent and complying with study procedures 6. Currently using or willing to use contraception, if woman of childbearing potential (such as condoms, IUD, or oral contraceptive), for duration of the study Exclusion Criteria: 1. Any history of opioid-use disorder 2. Any history of moderate- non-opioid (except for Nicotine) substance-use disorder 3. Any severity of alcohol use disorder (including mild) 4. Past or current psychosis, psychotic disorder (including psychotic MDD), mania, or bipolar disorder 5. Hamilton Rating Scale for Depression (HRSD) suicide item > 2 or Clinical Global Impressions (CGI)-Severity score of 7 at baseline 6. Previous or current treatment with tianeptine 7. Current treatment or currently taking an opioid 8. Failed depression treatment with electroconvulsive therapy, intravenous ketamine or esketamine 9. Acute, severe, or unstable medical illness 10. Weight > 300 lbs or girth size incompatible with scanner bore 11. Any physical or intellectual disability adversely affecting ability to complete assessments; MMSE <26 12. Having contraindication to MRI scanning (such as metal in body) or inability to tolerate the scanning procedures (e.g., severe obesity, claustrophobia) 13. Current pregnancy or currently breast feeding 14. Abnormal baseline liver function tests 15. Currently being treated with an antidepressant medication, an antipsychotic or mood stabilizer and not willing to end current treatment 16. Positive urine toxicity at screening (except for cannabinoid)


NCT ID:

NCT04249596


Primary Contact:

Principal Investigator
Steven Roose, MD
New York State Psychiatric Institute

Steven Roose, MD
Phone: 646-774-8661
Email: spr2@cumc.columbia.edu


Backup Contact:

Email: nicolas.cimino@nyspi.columbia.edu
Nicolas Cimino, BS
Phone: 646-774-8655


Location Contact:

New York, New York 10032
United States



There is no listed contact information for this specific location.

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: July 01, 2022

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