D-cycloserine Augmentation of Cognitive Remediation in Schizophrenia

NCT ID: NCT00963924

Last Updated: 2018-02-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-08-31
• Study Completion Date: 2011-06-30

Brief Summary

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.

Detailed 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.

Conditions

Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

D-cycloserine

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

Group Type: EXPERIMENTAL

D-cycloserine

Intervention Type: DRUG

50 mg by mouth one hour before first cognitive remediation session each week for eight weeks.

Cognitive Remediation

Intervention Type: BEHAVIORAL

40 one-hour daily sessions of cognitive remediation (Brain Fitness Program) over eight weeks.

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo by mouth one hour before first cognitive remediation session each week for eight weeks.

Cognitive Remediation

Intervention Type: BEHAVIORAL

40 one-hour daily sessions of cognitive remediation (Brain Fitness Program) over eight weeks.

Interventions

D-cycloserine

50 mg by mouth one hour before first cognitive remediation session each week for eight weeks.

Intervention Type: DRUG

Placebo

Placebo by mouth one hour before first cognitive remediation session each week for eight weeks.

Intervention Type: DRUG

Cognitive Remediation

40 one-hour daily sessions of cognitive remediation (Brain Fitness Program) over eight weeks.

Intervention Type: BEHAVIORAL

Other Intervention Names

Cycloserine; Brain Fitness Program

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Donald C. Goff, MD

Director of the Schizophrenia Clinical and Research Program

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Donald C. Goff, M.D.

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Countries

United States

References

Cain CK, McCue M, Bello I, Creedon T, Tang DI, Laska E, Goff DC. d-Cycloserine augmentation of cognitive remediation in schizophrenia. Schizophr Res. 2014 Mar;153(1-3):177-83. doi: 10.1016/j.schres.2014.01.016. Epub 2014 Jan 30.

Reference Type: RESULT

PMID: 24485587 (View on PubMed)

Other Identifiers

5P50MH060450

Identifier Type: NIH

Identifier Source: secondary_id

View Link

DATR A3-NSC

Identifier Type: -

Identifier Source: secondary_id

2008P002237

Identifier Type: -

Identifier Source: org_study_id