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Antidepressant Effects of the Glycine Receptor Antagonist AV-101 (4-chlorokynurenine) in Major Depressive Disorder

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2, 2017 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )
ClinicalTrials.gov Identifier:
NCT02484456
First received: June 26, 2015
Last updated: March 10, 2017
Last verified: March 2, 2017
  Purpose

Background:

- Drugs and talk therapy help treat depression, but these treatments usually take quite a bit of time to work. Ketamine is a fast-acting antidepressant, but it has side effects like unusual dreams and experiences. The drug AV-101 may have the same antidepressant effects but fewer side effects. Researchers want to see if it is effective and safe for people with major depressive disorder.

Objective:

- To see if the drug, AV-101 is safe and if it treats symptoms of major depressive disorder.

Eligibility:

- Adults ages 18 65 with major depression without psychotic features.

Design:

  • Participants will be screened under a separate protocol.
  • Participants will stay in the hospital for 12 14 weeks.
  • Phase 1 (2 7 weeks): participants will stop taking their medicines then not take any for 2 weeks. They will have several scans and other procedures.
  • Phase 2 (6 7 weeks): 2 weeks each of study drug and placebo once a day, with 2 weeks of no drugs in between.
  • Participants will have:
  • Physical exams
  • Interviews
  • Frequent blood collection. A needle will place a small plastic tube in the arm. Some blood samples will be taken through this tube.
  • 2 spinal taps (optional). The back will be numbed. A needle will insert a catheter between back bones. That will be left in for up to 30 hours. Spinal fluid will be collected through it.
  • 5 scans. Participants will lie in a machine with a magnetic field. The machine takes pictures of the brain and brain chemicals.
  • At the end of the study, participants will have medical evaluation, questions, and blood tests. Some may continue treatment at the clinic.

Condition Intervention Phase
Major Depression
Drug: AV 101 (4-Chlorokynurenine)
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Participant, Investigator
Primary Purpose: Treatment
Official Title: An Investigation of the Antidepressant Effects of the Glycine Receptor Antagonist AV 101 (4-chlorokynurenine) in Major Depressive Disorder

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Change from baseline in the Hamilton Depression Rating scale total score. [ Time Frame: Multiple timepoints ]

Secondary Outcome Measures:
  • Change from baseline in BPRS, CADSS, C-SSRS, HAM-A, HDRS, MADRS, PANAS, SHAPS, SSI, TEPS, YMRS total scores. [ Time Frame: Multiple ]
  • Change from baseline in the C-SSRS total score. [ Time Frame: Multiple ]
  • Proportion of subjects with response (defined as greater than or equal to 50% reduction from baseline in HDRS total score [ Time Frame: Multiple ]
  • Proportion of subjects in remission (defined as HDRS total score less than or equal to 7 [ Time Frame: End of test sessions ]
  • Incidence and nature of adverse events; vital signs; weight and body mass index (BMI) changes; physical examination changes; clinical laboratory evaluations; ECG. [ Time Frame: Multiple ]

Estimated Enrollment: 25
Study Start Date: June 18, 2015
Estimated Study Completion Date: December 31, 2019
Estimated Primary Completion Date: December 31, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Test Session 2
2 weeks of single daily dose of placebo pill
Other: Placebo
Placebo pill
Experimental: Test Session 1
2 weeks of 1,080 or 1,440 mg/day (single daily dose) of study drug
Drug: AV 101 (4-Chlorokynurenine)
Glycine Receptor Antagonist

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • 18 to 65 years of age.
  • Subjects must have a level of understanding sufficient to agree to all required tests and examinations, sign an informed consent document and verify understanding. To verify this, subjects must score greater than or equal to 80% on the consent quiz.
  • Subjects must fulfill DSM-IV criteria for MDD, single episode or recurrent without psychotic features, based on clinical assessment and confirmed by a structured diagnostic interview (SCID-P). Subjects must be experiencing a current major depressive episode of at least 4 weeks duration.
  • Subjects must have an initial score of at least 18 on the HDRS at screening and at baseline of study phase I.
  • Subjects must have a current or past history of lack of response to one adequate antidepressant trial (may be from the same chemical class) operationally defined using the modified-Antidepressant Treatment History Form (ATHF).

EXCLUSION CRITERIA:

  • Current psychotic features or a diagnosis of schizophrenia or any other psychotic disorder as defined in the DSM-IV.
  • Subjects with a history of DSM-IV drug or alcohol dependency or abuse (except for caffeine or nicotine dependence) within the preceding 3 months.
  • Head injury that results in loss of consciousness exceeding 5 minutes (for the imaging component of the study).
  • Subjects with a DSM IV Axis II diagnosis of borderline or antisocial personality disorder.
  • Pregnant or nursing women or women of child bearing potential not using at least 1 medically accepted means of contraception from the time of enrollment in the study until 1 month after completion of the second phase. Examples of medically accepted means of contraception include oral, injectable, or implant birth control, condom, diaphragm with spermicide, intrauterine devices (IUD), tubal ligation, abstinence or partner with vasectomy. .
  • Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.
  • Subjects with clinical hyperthyroidism or hypothyroidism.
  • Subjects with one or more seizures without a clear and resolved etiology.
  • Clinically significant abnormal laboratory tests.
  • Treatment with a reversible monoamine oxidase inhibitor (MAOI) within 4 weeks of study phase II.
  • Treatment with fluoxetine or aripirazole within 5 weeks of study phase II.
  • Treatment with any other disallowed concomitant medication or TMS 14 days before randomization.
  • Treatment with clozapine or electroconvulsive therapy (ECT) within 1 month of randomization.
  • Lifetime history of deep brain stimulation.
  • Subjects who, in the Principal Investigator s judgment, pose a current serious suicidal or homicidal risk.
  • Positive HIV test
  • Contraindications to MRS (metal in body, claustrophobia, etc for imaging)
  • No structured psychotherapy will be permitted during the total duration of the study. Subjects unable or unwilling to stop psychotherapy will be unable to participate in the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02484456

Contacts
Contact: Libby Jolkovsky (877) 646-3644 libby_jolkovsky@nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
National Institute of Mental Health (NIMH)
Investigators
Principal Investigator: Carlos A Zarate, M.D. National Institute of Mental Health (NIMH)
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier: NCT02484456     History of Changes
Other Study ID Numbers: 150151
15-M-0151
Study First Received: June 26, 2015
Last Updated: March 10, 2017

Keywords provided by National Institutes of Health Clinical Center (CC):
Major Depression
Glycine Receptor Antagonist
4-Chlorokyneurenine
Treatment Resistant
Glutamatergic System

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders
Antidepressive Agents
Glycine
Psychotropic Drugs
Glycine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on March 27, 2017