Once Weekly D-cycloserine for Schizophrenia

Sponsor

Massachusetts General Hospital (Other)

Overall Status

Withdrawn

CT.gov ID

NCT00964041

Collaborator

National Institute of Mental Health (NIMH) (NIH)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a parallel-group, placebo-controlled trial examining the cognitive effects at weeks 1, 4, & 8 of once-weekly oral D-cycloserine 50 mg added to a stable dose of antipsychotic for 8 weeks in adult outpatients with schizophrenia.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: D-cycloserine Drug: Placebo	Phase 4

Detailed Description

In a previous placebo-controlled trial, investigators demonstrated significant improvement of negative symptoms with once-weekly D-cycloserine treatment. In addition, investigators found significant improvement of memory consolidation following the first dose; however, the effect on memory consolidation was lost after several weeks. The "practice effect" of weekly measurement of memory consolidation using repeated administration of the Logical Memory Test may have resulted in a "ceiling effect" which would obscure drug/placebo differences. In the current study, investigators propose to administer the Logical Memory Test at four-week intervals (weeks 1, 4 and 8) to avoid the ceiling effect. Additionally a measurement will be added of negative symptoms at week 4 to better characterize the time course of negative symptom improvement.

Hypotheses:

Assess the effects of a single dose of D-cycloserine 50 mg on memory consolidation as measured by the Logical Memory Test compared to placebo.
Assess the persistence of once-weekly D-cycloserine effects on memory consolidation measured at weeks 4 & 8.
Assess the effects of repeated weekly dosing of D-cycloserine on performance on a standard cognitive battery at week 8 compared to placebo.
Assess effects of weekly D-cycloserine dosing on negative symptoms at weeks 4 & 8 compared to placebo.
Assess tolerability and side effects of weekly D-cycloserine compared to placebo.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Effects of Weekly Dosing of D-cycloserine on Cognitive Function in Individuals With Schizophrenia.

Study Start Date :

Jul 1, 2009

Actual Primary Completion Date :

Jun 1, 2011

Actual Study Completion Date :

Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: D-cycloserine Participants will receive D-cycloserine weekly, one hour before any assessments, for eight weeks.	Drug: D-cycloserine 50 mg by mouth weekly, one hour before assessments, for eight weeks. Other Names: Seromycin Cycloserine
Placebo Comparator: Placebo Participants will receive placebo weekly, one hour before any assessments, for eight weeks.	Drug: Placebo Placebo by mouth, weekly, one hour before any assessments, each week for eight weeks.

Arm

Intervention/Treatment

Experimental: D-cycloserine

Participants will receive D-cycloserine weekly, one hour before any assessments, for eight weeks.

Drug: D-cycloserine

50 mg by mouth weekly, one hour before assessments, for eight weeks.

Other Names:

Seromycin

Cycloserine

Placebo Comparator: Placebo

Participants will receive placebo weekly, one hour before any assessments, for eight weeks.

Drug: Placebo

Placebo by mouth, weekly, one hour before any assessments, each week for eight weeks.

Outcome Measures

Primary Outcome Measures

Effect of repeated weekly dosing of D-cycloserine on performance on a standard cognitive battery. [Baseline (Week 0) and End of Study (Week 8)]

Secondary Outcome Measures

Effects of weekly D-cycloserine dosing on negative symptoms at weeks 4 & 8 compared to placebo. [Baseline (Week 0) and End of Study (Week 8)]
Effect of a single dose of D-cycloserine 50 mg on memory consolidation as measured by the Logical Memory Test compared to placebo. [Same Day (Single Dose - Week 1)]
Assess the persistence of once-weekly D-cycloserine effects on memory consolidation measured at weeks 4 & 8. [Week 4 and Week 8]
Assess tolerability and side effects of weekly D-cycloserine compared to placebo [Weekly measurements for 8 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female
Age 18-65 years
Diagnosis of schizophrenia or schizoaffective disorder, depressed type
Stable dose of antipsychotic for at least 4 weeks.
Able to provide informed consent
Able to complete a cognitive battery

Exclusion Criteria:

Current treatment with clozapine
Dementia
Seizure disorder
Unstable medical illness
Active substance abuse
Pregnancy, nursing, or unwilling to use appropriate birth control measures during participation if female and fertile.
Severe renal insufficiency (Serum creatinine > 1.5 mg/dL)