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

Study Overview
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Brief Summary
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The study aims to assess the effects of single dose and repeated weekly dosing of 50mg d-cycloserine versus placebo on cognitive and memory functioning in schizophrenia patients. The study will also examine the effects of 50mg d-cycloserine on positive symptoms and negative symptoms, as well as assess tolerability and side-effects.

Detailed Description
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This is a ten-week, parallel-group, placebo-controlled trial examining the cognitive effects at weeks 1, 2, 3. 4, 5, 6, 7, 8 & 10 of once-weekly oral D-cycloserine 50 mg added to a stable dose of antipsychotic for 8 weeks in 60 adult outpatients with schizophrenia. Specific aims: Assess the effects of a single dose of D-cycloserine 50 mg on cognitive functioning compared to placebo. Assess the effects of repeated weekly dosing of D-cycloserine on cognitive functioning at week 8 compared to placebo. Assess the effects of repeated weekly dosing of D-cycloserine on memory functioning once a week 1 hour after medication administration compared to placebo. Assess the persistence of learned information in a no-treatment follow-up assessment at Week 10 in the D-cycloserine group compared to the placebo group. Assess effects of weekly D-cycloserine dosing on positive & negative symptoms at week 8 compared to placebo. Assess tolerability and side effects of weekly D-cycloserine compared to placebo. Assess the effects of d-cycloserine dosed weekly for seven weeks on reward responsiveness as measured with the response bias task compared with placebo. Assess the effects of d-cycloserine dosed weekly for seven weeks on measures of functioning.

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

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: d-cycloserine


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.

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>50 mg d-cycloserine | Drug: d-cycloserine<br>* 50mg dose d-cycloserine v placebo<br>|
| Placebo Comparator: Placebo<br>50 mg placebo | Drug: d-cycloserine<br>* 50mg dose d-cycloserine v placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Main Outcome Measure: The Change From Baseline to Week 8 on the SANS | The change from baseline to week 8 on the scale for the assessment of negative symptoms (SANS) total score. Total SANS scores range from 0-100. The SANS is comprised of 5 subscores: Affective Flattening or Blunting (score range 0-35), Alogia (score range 0-20), Avolition-Apathy (score range 0-15), Anhedonia-Asociality (score range 0-20), and Attention (0-10). For each scale, the higher the score the more prominent the negative symptoms were. The total score was computed by adding all the subscale total scores. To compute change in scores, week 8 scores were subtracted from baseline scores, resulting in a change score. Higher values equals greater improvement (i.e. week 8 score was lower than baseline score). | Baseline score vs. Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Effects on the Positive Syndrome Subscale of the PANSS | The change from baseline to week 8 on the positive symptom sub-scale of the Positive and Negative Syndrome Scale (PANSS). Total PANSS positive symptom sub-scale scores range from 7-49. The PANSS positive symptom sub-scale is comprised of 7 items rated on a scale of 1-7: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. A score of one on each item 1 absent, 2 is minimal, 3 is mild, 4 is moderate, 5 is moderately severe, 6 is severe, and 7 is extreme. The total score was computed by adding all the items on the sub-scale together. To compute change in scores, week 8 scores were subtracted from baseline scores, resulting in a change score. Higher values equals greater improvement (i.e. week 8 score was lower than baseline score). | Baseline score vs. Week 8 score | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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schizophrenia, cognition, d-cycloserine, memory