D-cycloserine for Major Depressive Disorder

Major Depressive Disorder Clinical Trial

Official title:

N-methyl-D-aspartate Receptor (NMDAR)-Based Pharmacotherapy With D-cycloserine for Treatment-resistant Major Depressive Disorder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00408031
• Other study ID #: Heresco 4 CTIL
• Secondary ID: Herzog - protoco
• Status: Completed
• Phase: Phase 2
• First received: December 3, 2006
• Last updated: August 2, 2012
• Start date: January 2007
• Est. completion date: May 2010

Study information

• Verified date: August 2012
• Source: Herzog Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

Other known NCT identifiers

• NCT00781014

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: May 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

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.

Locations

Country	Name	City	State
Israel	Ezrath Nashim - Herzog Memorial Hospital	Jerusalem
Israel	Ezrath Nashim - Herzog Memorial Hospital & Community Clinics	Jerusalem

Sponsors (2)

Lead Sponsor	Collaborator
Herzog Hospital	National Alliance for Research on Schizophrenia and Depression

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in 24 item Hamilton Depression Rating Scale (HAMD) scores. Safety measures: UKU scale, vital signs assessments, laboratory parameters (SMA-20, CBC, UA)		6 weeks	Yes
Primary	Change in Hamilton Rating Scale for Anxiety (HAMA) scores.		6 weeks	No