D-cycloserine for Major Depressive Disorder

This study has been completed.
Sponsor:
Collaborator:
National Alliance for Research on Schizophrenia and Depression
Information provided by (Responsible Party):
Heresco-Levi Uriel, Herzog Hospital
ClinicalTrials.gov Identifier:
NCT00408031
First received: December 3, 2006
Last updated: August 2, 2012
Last verified: August 2012
  Purpose

For many depression patients treatment changes are required, including switching to another antidepressant and addition of a second antidepressant or a non-antidepressant agent ("augmentation"). The need to modify treatment is usually necessary because of partial or no response to first-line monotherapy or the failure to achieve remission although treatment response (improvement) has been obtained. These caveats of presently available antidepressant drugs highlight the need for innovative pharmacological treatment strategies. Recent data suggest that N-methyl-D-aspartate receptor (NMDAR) antagonists and partial agonists at the NMDAR-associated glycine binding site may represent a novel type of antidepressant medications. These types of compounds protect vulnerable neurons against a variety of insults, including stress-induced damage, and may serve to enhance and maintain normal synaptic connectivity. In animal models, these compounds mimic the effects of clinically effective antidepressants. Furthermore, down-regulation of the glycine site of the NMDAR was found to be a common feature of currently used antidepressant medications. D-cycloserine (DCS , Seromycin) is a broad spectrum antibiotic, in use for over thirty years against tuberculosis, that acts as a partial agonist at the NMDAR-associated glycine site. Beneficial antidepressant effects have been reported with 500-1000 mg/day DCS regimens in depressed tuberculosis patients and recent preliminary findings suggest that DCS may also be beneficial in the treatment of major depressive disorder. The antidepressant effects of DCS seem to reflect consequences of its capacity to reduce NMDAR receptor function. In the present project, it is proposed to assess, using a random assignment, parallel-group, double blind, placebo controlled design, the effects of a NMDAR -antagonist DCS dose regimen, 250 --> 1000 mg/day for 6 wks, as adjuvant pharmacotherapy for treatment-resistant major depressive disorder patients. The study methodology includes the assessment of DCS effects upon symptoms profile, neurocognitive tests performance, amino acids serum levels, and brain electrophysiology parameters associated with the prepulse inhibition-startle response paradigm. It is hypothesized that significant beneficial DCS treatment effects will be registered.


Condition Intervention Phase
Major Depressive Disorder
Drug: D-cycloserine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: N-methyl-D-aspartate Receptor (NMDAR)-Based Pharmacotherapy With D-cycloserine for Treatment-resistant Major Depressive Disorder

Resource links provided by NLM:


Further study details as provided by Herzog Hospital:

Primary Outcome Measures:
  • Change in 24 item Hamilton Depression Rating Scale (HAMD) scores. Safety measures: UKU scale, vital signs assessments, laboratory parameters (SMA-20, CBC, UA) [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
  • Change in Hamilton Rating Scale for Anxiety (HAMA) scores. [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

Enrollment: 26
Study Start Date: January 2007
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Randomization to 2 treatment groups. One group receives adjuvant treatment with D-cycloserine, up to 1 g/day. The second group receives adjuvant treatment with placebo, up to 1 g/day.
Drug: D-cycloserine
D-cycloserine (DCS , Seromycin) is a broad spectrum antibiotic, in use for over thirty years against tuberculosis, that acts as a partial agonist at the NMDAR-associated GLY site.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • DSM-IV diagnosis of major depression .
  • HAMD scale score of ≥20 despite at least two adequate antidepressant treatment trials during the current episode.

Exclusion Criteria:

  • Underwent ECT treatment during the 3 months preceding the study.
  • Change in psychotropic medications doses during the 3 weeks preceding the study.
  • Concurrent unstable medical or neurological illness.
  • Patients are judged to be potentially violent towards themselves or others, or have a history of drug/alcohol abuse.
  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: NCT00408031

Locations
Israel
Ezrath Nashim - Herzog Memorial Hospital & Community Clinics
Jerusalem, Israel
Ezrath Nashim - Herzog Memorial Hospital
Jerusalem, Israel
Sponsors and Collaborators
Herzog Hospital
National Alliance for Research on Schizophrenia and Depression
Investigators
Principal Investigator: Uriel Heresco-Levy, M.D. Ezrath Nashim - Herzog Memorial Hospital
  More Information

No publications provided

Responsible Party: Heresco-Levi Uriel, Princepal Investigator, Herzog Hospital
ClinicalTrials.gov Identifier: NCT00408031     History of Changes
Obsolete Identifiers: NCT00781014
Other Study ID Numbers: Heresco 4 CTIL, Herzog - protocol 5372
Study First Received: December 3, 2006
Last Updated: August 2, 2012
Health Authority: Israel: Ministry of Health

Keywords provided by Herzog Hospital:
Major depressive disorder
NMDA receptor
Treatment-Resistant
D-cycloserine

Additional relevant MeSH terms:
Depressive Disorder
Depression
Depressive Disorder, Major
Mood Disorders
Mental Disorders
Behavioral Symptoms
N-Methylaspartate
Cycloserine
Excitatory Amino Acid Agonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Anti-Infective Agents, Urinary
Anti-Infective Agents
Therapeutic Uses
Renal Agents
Antibiotics, Antitubercular
Anti-Bacterial Agents
Antitubercular Agents
Antimetabolites

ClinicalTrials.gov processed this record on July 24, 2014