Once Weekly D-cycloserine for Schizophrenia

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: D-cycloserine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: D-cycloserine<br>Participants will receive D-cycloserine weekly, one hour before any assessments, for eight weeks. | Drug: D-cycloserine<br>* 50 mg by mouth weekly, one hour before assessments, for eight weeks.<br>* Other names: Cycloserine;|
| Placebo Comparator: Placebo<br>Participants will receive placebo weekly, one hour before any assessments, for eight weeks. | Drug: Placebo<br>* Placebo by mouth, weekly, one hour before any assessments, each week for eight weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cognitive Impairment, Neuroplasticity, D-cycloserine, N-methyl-D-aspartate (NMDA), Anti-Bacterial Agents, Mental Disorders, Psychotic Disorders, Antitubercular Agents, Schizophrenia and Disorders with Psychotic Features, Schizoaffective Disorder