Schizophrenia
Conditions
Keywords
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
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.
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: 1. 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. 2. Assess the persistence of once-weekly D-cycloserine effects on memory consolidation measured at weeks 4 & 8. 3. Assess the effects of repeated weekly dosing of D-cycloserine on performance on a standard cognitive battery at week 8 compared to placebo. 4. Assess effects of weekly D-cycloserine dosing on negative symptoms at weeks 4 & 8 compared to placebo. 5. Assess tolerability and side effects of weekly D-cycloserine compared to placebo.
Interventions
DRUGD-cycloserine
50 mg by mouth weekly, one hour before assessments, for eight weeks.
DRUGPlacebo
Placebo by mouth, weekly, one hour before any assessments, each week for eight weeks.
Sponsors
National Institute of Mental Health (NIMH)
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female 2. Age 18-65 years 3. Diagnosis of schizophrenia or schizoaffective disorder, depressed type 4. Stable dose of antipsychotic for at least 4 weeks. 5. Able to provide informed consent 6. Able to complete a cognitive battery
Exclusion criteria
1. Current treatment with clozapine 2. Dementia 3. Seizure disorder 4. Unstable medical illness 5. Active substance abuse 6. Pregnancy, nursing, or unwilling to use appropriate birth control measures during participation if female and fertile. 7. Severe renal insufficiency (Serum creatinine \> 1.5 mg/dL)
Design outcomes
Primary
| Measure | 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
| Measure | 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 |
Countries
United States
Outcome results
None listed