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Sponsors and Collaborators: |
Herzog Hospital National Alliance for Research on Schizophrenia and Depression |
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Information provided by: | Herzog Hospital |
ClinicalTrials.gov Identifier: | NCT00408031 |
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 |
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Major Depressive Disorder |
Drug: D-cycloserine |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Efficacy Study |
Official Title: | N-Methyl-D-Aspartate Receptor (NMDAR)-Based Pharmacotherapy With D-Cycloserine for Treatment-Resistant Major Depressive Disorder |
Estimated Enrollment: | 40 |
Study Start Date: | January 2007 |
Estimated Study Completion Date: | January 2010 |
Estimated Primary Completion Date: | January 2009 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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1: Experimental
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.
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Ages Eligible for Study: | 18 Years to 75 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: Uriel Heresco-Levy, M.D. | 972-2-5316906 | Heresco@md.huji.ac.il |
Contact: Baruch Shapira, M.D | 972-2-5316928 | shapirab@md.huji.ac.il |
Israel | |
Ezrath Nashim - Herzog Memorial Hospital & Community Clinics | Recruiting |
Jerusalem, Israel | |
Contact: Uriel Heresco-Levy, M.D. 972-2-5316906 Heresco@md.huji.ac.il | |
Contact: Baruch Shapira, M.D. 972-2-5316928 | |
Ezrath Nashim - Herzog Memorial Hospital | Not yet recruiting |
Jerusalem, Israel | |
Contact: Uriel Heresco-Levy, M.D. 972-2-5316906 Heresco@md.huji.ac.il | |
Contact: Baruch Shapira, M.D. 972-2-5316928 shapirab@md.huji.ac.il | |
Principal Investigator: Uriel Heresco-Levy, M.D. | |
Sub-Investigator: Baruch Shapira, M.D. | |
Sub-Investigator: Yevgenia Gelfin, M.D. |
Principal Investigator: | Uriel Heresco-Levy, M.D. | Ezrath Nashim - Herzog Memorial Hospital |
Responsible Party: | Herzog Hospital ( Uriel Heresco-Levy ) |
Study ID Numbers: | Heresco 4 CTIL, Herzog - protocol 5372 |
Study First Received: | December 3, 2006 |
Last Updated: | August 6, 2008 |
ClinicalTrials.gov Identifier: | NCT00408031 History of Changes |
Health Authority: | Israel: Ministry of Health |
Major depressive disorder NMDA receptor Treatment-Resistant D-cycloserine |
Cycloserine Antimetabolites Anti-Infective Agents Depression Aspartic Acid Anti-Infective Agents, Urinary Depressive Disorder, Major |
Depressive Disorder N-Methylaspartate Behavioral Symptoms Anti-Bacterial Agents Mental Disorders Mood Disorders Antitubercular Agents |
Antimetabolites Cycloserine Anti-Infective Agents Depression Disease Molecular Mechanisms of Pharmacological Action Anti-Infective Agents, Urinary Depressive Disorder, Major Renal Agents Depressive Disorder |
Pharmacologic Actions Antibiotics, Antitubercular Behavioral Symptoms Anti-Bacterial Agents Pathologic Processes Mental Disorders Therapeutic Uses Mood Disorders Antitubercular Agents |