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Tianeptine for Treatment Resistant Depression

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04249596
Recruitment Status : Recruiting
First Posted : January 31, 2020
Last Update Posted : September 17, 2021
Icahn School of Medicine at Mount Sinai
Information provided by (Responsible Party):
Jonathan A. Javitch, MD, PhD, New York State Psychiatric Institute

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Treatment Resistant Depression Drug: Tianeptine Sodium Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Tianeptine for Treatment Resistant Depression
Actual Study Start Date : October 14, 2020
Estimated Primary Completion Date : March 1, 2022
Estimated Study Completion Date : March 1, 2022

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Open Treatment
All subjects will be treated for 8 weeks of treatment with Tianeptine (Tianeurax 12.5 mg) 3 times a day (9am, 1pm, 5pm).
Drug: Tianeptine Sodium
At baseline, and following 8 weeks of treatment with tianeptine(12.5 mg, 3x daily), participants will be assessed in a number of procedures to evaluate their emotional and physical pain state and pain stimulus response and the relationship of such states/responses to endogenous opioid signaling. To further assess emotional pain, participants will also undergo fMRI while performing a validated social rejection and social acceptance paradigm known to induce endogenous opioid release in control subjects and blunted release in MDD. Examining both rejection and acceptance is important because the MOR system regulates both social distress and social reward in animals and humans, and tianeptine may also act on abnormal MOR-mediated responses to social acceptance in MDD. Likewise, a second fMRI scan will be used to explore physical pain response using an established thermal pain sensitivity task.
Other Name: Tianeurex 12.5 mg

Primary Outcome Measures :
  1. Hamilton Rating Scale for Depression (HRSD) [ Time Frame: Baseline ]
    Our target is depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD). The HRSD is a 24-item questionnaire used as an indication of depression and a guide to evaluate recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score of 16 or above is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity.

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04249596

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Contact: Bret R Rutherford, MD 646-774-8660
Contact: Benjamin Ciener, BA 646-774-8664

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United States, New York
1051 Riverside Drive Recruiting
New York, New York, United States, 10032
Principal Investigator: Bret R Rutherford, M.D.         
Sponsors and Collaborators
New York State Psychiatric Institute
Icahn School of Medicine at Mount Sinai
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Principal Investigator: Bret R Rutherford, MD New York State Psychiatric Institute
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Responsible Party: Jonathan A. Javitch, MD, PhD, Professor of Pharmacology, New York State Psychiatric Institute Identifier: NCT04249596    
Other Study ID Numbers: 7944
First Posted: January 31, 2020    Key Record Dates
Last Update Posted: September 17, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Depressive Disorder
Depressive Disorder, Treatment-Resistant
Behavioral Symptoms
Mood Disorders
Mental Disorders
Antidepressive Agents, Tricyclic
Antidepressive Agents
Psychotropic Drugs