Clinical trial NCT00963924: D-cycloserine Augmentation of Cognitive Remediation in Schizophrenia
Official title: A Placebo-controlled Trial of D-cycloserine Augmentation of Cognitive Remediation in Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Schizophrenia
Keywords: Cognitive Impairment
Neuroplasticity
D-cycloserine
NMDA
Anti-Bacterial Agents
Mental Disorders
Psychotic Disorders
Antitubercular Agents
Schizophrenia and Disorders with Psychotic Features
Schizoaffective Disorder
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2009-08-24
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS)
timeFrame: Baseline vs. Week 8
measure: Scale for Assessment of Negative Symptoms (SANS)
timeFrame: Baseline vs. Week 8
measure: Auditory Discrimination Task: Interstimulus Interval (ISI)
timeFrame: Baseline vs. Week 8
Secondary outcomes:
measure: Positive and Negative Syndrome Scale (PANSS)
timeFrame: Baseline
measure: Global Assessment of Functioning Scale (GAS)
timeFrame: Baseline
measure: Heinrich Quality of Life Scale (QoL)
timeFrame: Baseline
measure: Calgary Depression Scale for Schizophrenia (CDSS)
timeFrame: Baseline
measure: Clinical Global Impression (CGI)
timeFrame: Weeks 0 and 8, and Month 6 after cognitive remediation completion
measure: Side Effects Checklist (SEC)
timeFrame: Weeks 0 - 8, and Month 6 after cognitive remediation completion
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Donald C. Goff, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.