Once Weekly D-cycloserine for Schizophrenia

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: D-cycloserine; Drug: Placebo

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.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: D-cycloserine; Participants will receive D-cycloserine weekly, one hour before any assessments, for eight weeks.	Drug: D-cycloserine; 50 mg by mouth weekly, one hour before assessments, for eight weeks.; Other Names: Cycloserine; Seromycin
Placebo Comparator: Placebo; Participants will receive placebo weekly, one hour before any assessments, for eight weeks.	Drug: Placebo; Placebo by mouth, weekly, one hour before any assessments, each week for eight weeks.

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Donald C Goff, M.D., Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: August 20, 2009
• First Submitted That Met QC Criteria: August 20, 2009
• First Posted (Estimate): August 24, 2009

Study Record Updates

• Last Update Posted (Estimate): November 20, 2013
• Last Update Submitted That Met QC Criteria: November 19, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: Neuroplasticity; Cognitive Impairment; Schizoaffective Disorder; Mental Disorders; D-cycloserine; Psychotic Disorders; Antitubercular Agents; Anti-Bacterial Agents; Schizophrenia and Disorders with Psychotic Features; N-methyl-D-aspartate (NMDA)
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antimetabolites; Anti-Bacterial Agents; Antitubercular Agents; Antibiotics, Antitubercular; Anti-Infective Agents, Urinary; Renal Agents; Cycloserine
• Other Study ID Numbers: 2009-P-001341; P50MH060450 (U.S. NIH Grant/Contract); DATR A3-NSC (National Institute of Mental Health)