D-cycloserine Augmentation of Cognitive Remediation in Schizophrenia

Mass General Brigham

Status: Completed

Conditions: Schizophrenia

Treatments: Drug: Placebo; Behavioral: Cognitive Remediation; Drug: D-cycloserine

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00963924

DATR A3-NSC

2008P002237

5P50MH060450 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

This study seeks to examine the effects of D-cycloserine augmentation on cognitive remediation for patients diagnosed with schizophrenia. We will test the hypotheses that D-cycloserine will significantly improve cognitive performance, negative symptoms, and measures of functioning compared to placebo when combined with eight weeks of cognitive remediation. We expect that these effects will persist when assessed at six-month follow up.

Full description

D-cycloserine has been shown to enhance learning in animal models and, in a previous trial, once-weekly D-cycloserine improved negative symptoms in schizophrenia subjects. We set out to test whether DCS combined with cognitive remediation would improve learning of a practiced auditory discrimination task and whether gains would generalize to unpracticed cognitive tasks.

The proposed study consists of an 8-week, placebo-controlled, double-blind, parallel-group trial of D-cycloserine augmentation of cognitive remediation in schizophrenia outpatients. The primary outcome measure is change in performance on the MATRICS cognitive battery composite score after 8 weeks. Secondary outcome measures include a measure of processing speed assessed after weeks 1, 2, 4 & 8, and changes in negative symptoms and measures of functioning after 4 and 8 weeks. In addition, all outcome measures will be repeated at 6 months to assess persistence of benefit.

Hypotheses:

1. D-cycloserine will significantly improve cognitive performance as measured by the composite score on the MATRICS battery compared to placebo after 8 weeks of cognitive remediation.
2. D-cycloserine will significantly improve negative symptoms as measured by the SANS compared to placebo after 8 weeks when combined with cognitive remediation.
3. D-cycloserine will significantly improve measures of functioning (GAS, QoL and CGI) at 8 weeks compared to placebo when combined with cognitive remediation.
4. D-cycloserine effects on cognition, negative symptoms and functioning will persist compared to placebo when assessed at 6-month follow-up.

Enrollment: 54 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No 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
• Able to perform the cognitive remediation exercises

Exclusion criteria

• Current treatment with clozapine
• Dementia
• Seizure disorder
• Unstable medical illness
• Renal insufficiency measured as eGFR >60mg/dL/min
• Active substance abuse: positive urine toxic screen
• Pregnancy, nursing, or unwilling to use appropriate birth control measures during participation if female and fertile.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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54 participants in 2 patient groups, including a placebo group

D-cycloserine

Experimental group

Description:

Participants will receive D-cycloserine weekly, one hour before the first cognitive remediation session of the week, for eight weeks.

Treatment:

Drug: D-cycloserine

Behavioral: Cognitive Remediation

Placebo

Placebo Comparator group

Description:

Participants will receive placebo weekly, one hour before the first cognitive remediation session of the week, for eight weeks.

Treatment:

Behavioral: Cognitive Remediation

Drug: Placebo