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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Donald C. Goff, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00455702
First received: April 2, 2007
Last updated: July 14, 2014
Last verified: July 2014
  Purpose

The study aims to assess the effects of single dose and repeated weekly dosing of 50mg d-cycloserine versus placebo on cognitive and memory functioning in schizophrenia patients. The study will also examine the effects of 50mg d-cycloserine on positive symptoms and negative symptoms, as well as assess tolerability and side-effects.


Condition Intervention Phase
Schizophrenia
Drug: d-cycloserine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Weekly Dosing of D-cycloserine on Cognitive Function in Individuals

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Main Outcome Measure: The Change From Baseline to Week 8 on the SANS [ Time Frame: Baseline score vs. Week 8 ] [ Designated as safety issue: No ]
    The change from baseline to week 8 on the scale for the assessment of negative symptoms (SANS) total score. Total SANS scores range from 0-100. The SANS is comprised of 5 subscores: Affective Flattening or Blunting (score range 0-35), Alogia (score range 0-20), Avolition-Apathy (score range 0-15), Anhedonia-Asociality (score range 0-20), and Attention (0-10). For each scale, the higher the score the more prominent the negative symptoms were. The total score was computed by adding all the subscale total scores. To compute change in scores, week 8 scores were subtracted from baseline scores, resulting in a change score. Higher values equals greater improvement (i.e. week 8 score was lower than baseline score).


Secondary Outcome Measures:
  • Treatment Effects on the Positive Syndrome Subscale of the PANSS [ Time Frame: Baseline score vs. Week 8 score ] [ Designated as safety issue: No ]
    The change from baseline to week 8 on the positive symptom sub-scale of the Positive and Negative Syndrome Scale (PANSS). Total PANSS positive symptom sub-scale scores range from 7-49. The PANSS positive symptom sub-scale is comprised of 7 items rated on a scale of 1-7: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. A score of one on each item 1 absent, 2 is minimal, 3 is mild, 4 is moderate, 5 is moderately severe, 6 is severe, and 7 is extreme. The total score was computed by adding all the items on the sub-scale together. To compute change in scores, week 8 scores were subtracted from baseline scores, resulting in a change score. Higher values equals greater improvement (i.e. week 8 score was lower than baseline score).


Enrollment: 38
Study Start Date: July 2004
Study Completion Date: April 2007
Primary Completion Date: April 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: D-cycloserine
50 mg d-cycloserine
Drug: d-cycloserine
50mg dose d-cycloserine v placebo
Placebo Comparator: Placebo
50 mg placebo
Drug: d-cycloserine
50mg dose d-cycloserine v placebo

Detailed Description:

This is a ten-week, parallel-group, placebo-controlled trial examining the cognitive effects at weeks 1, 2, 3. 4, 5, 6, 7, 8 & 10 of once-weekly oral D-cycloserine 50 mg added to a stable dose of antipsychotic for 8 weeks in 60 adult outpatients with schizophrenia.

Specific aims:

  1. Assess the effects of a single dose of D-cycloserine 50 mg on cognitive functioning compared to placebo.
  2. Assess the effects of repeated weekly dosing of D-cycloserine on cognitive functioning at week 8 compared to placebo.
  3. Assess the effects of repeated weekly dosing of D-cycloserine on memory functioning once a week 1 hour after medication administration compared to placebo.
  4. Assess the persistence of learned information in a no-treatment follow-up assessment at Week 10 in the D-cycloserine group compared to the placebo group.
  5. Assess effects of weekly D-cycloserine dosing on positive & negative symptoms at week 8 compared to placebo.
  6. Assess tolerability and side effects of weekly D-cycloserine compared to placebo.
  7. Assess the effects of d-cycloserine dosed weekly for seven weeks on reward responsiveness as measured with the response bias task compared with placebo.
  8. Assess the effects of d-cycloserine dosed weekly for seven weeks on measures of functioning.
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00455702

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Donald C Goff, M.D. Massachusetts General Hospital
  More Information

Publications:
Responsible Party: Donald C. Goff, MD, Director of the Schizophrenia Clinical and Research Program, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00455702     History of Changes
Other Study ID Numbers: 2005-P-001040
Study First Received: April 2, 2007
Results First Received: June 11, 2014
Last Updated: July 14, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
schizophrenia
cognition
d-cycloserine
memory

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Cycloserine
Anti-Infective Agents, Urinary
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Renal Agents
Antibiotics, Antitubercular
Anti-Bacterial Agents
Antitubercular Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014