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D-cycloserine Augmentation of Cognitive Remediation in Schizophrenia

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Donald C. Goff, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00963924
First received: August 20, 2009
Last updated: July 31, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention
Schizophrenia
Drug: D-cycloserine
Drug: Placebo
Behavioral: Cognitive Remediation

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Placebo-controlled Trial of D-cycloserine Augmentation of Cognitive Remediation in Schizophrenia

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) [ Time Frame: Baseline vs. Week 8 ] [ Designated as safety issue: No ]
    Change of a composite score from baseline to week 8 on the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS). The MATRICS consists of 10 cognitive tasks that are used to calculate scores in 7 cognitive domains: speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. The raw scores on each cognitive task are transformed into t-scores, and then these scores are used to calculate the domain scores. The composite score is calculated by averaging all domain t-scores to come up with one overall cognitive composite t-score. For all scores on the assessment, the higher the score the better the performance on the task.


Secondary Outcome Measures:
  • Positive and Negative Syndrome Scale (PANSS) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    The baseline score 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. The higher a score the more prominent a positive symptom is.

  • Scale for Assessment of Negative Symptoms (SANS) [ Time Frame: Baseline vs. Week 8 ] [ Designated as safety issue: No ]
    The total scores from baseline and 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 sub-scale total scores. Scores are reported for baseline and week 8.

  • Global Assessment of Functioning Scale (GAS) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    The Global Assessment of Functioning Scale (GAS) measured at baseline. This scale measures social, occupational, and psychological functioning, on a scale of 0-100. The higher the score, the greater a participant's functioning level.

  • Heinrich Quality of Life Scale (QoL) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Baseline scores of the Heinrich Quality of Life Scale, a 21 item scale designed and validated to measure intrapsychic foundations, interpersonal relations, instrumental role, and common objects and activities in patients diagnosed with Schizophrenia. Patients are rated on each of the 21 items on a scale of 0-6. Total scores are computed by adding up the scores of each individual item, with a total score ranging from 0-126. Higher scores reflect higher functioning.

  • Calgary Depression Scale for Schizophrenia (CDSS) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Baseline scores on the Calgary Depression Scale for Schizophrenia (CDSS). Total CDSS scores range from 0-27. The assessment is comprised of 9 questions covering the topics of Depression, Hopelessness, Self Depreciation, Guilty Ideas of Reference, Pathological Guilt, Morning Depression, Early Wakening, Suicide, Observed Depression. Each item is scored on a scale from 0-3 (0 = absent, 1 = mild, 2 = moderate, 3 = severe). The total score is computed by adding up the individual scores of each item. The higher the score, the more prominent the symptoms of depression are for the participant.

  • Clinical Global Impression (CGI) [ Time Frame: Weeks 0 and 8, and Month 6 after cognitive remediation completion ] [ Designated as safety issue: No ]
  • Side Effects Checklist (SEC) [ Time Frame: Weeks 0 - 8, and Month 6 after cognitive remediation completion ] [ Designated as safety issue: Yes ]

Enrollment: 54
Study Start Date: August 2009
Study Completion Date: June 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: D-cycloserine
Participants will receive D-cycloserine weekly, one hour before the first cognitive remediation session of the week, for eight weeks.
Drug: D-cycloserine
50 mg by mouth one hour before first cognitive remediation session each week for eight weeks.
Other Name: Cycloserine
Behavioral: Cognitive Remediation
40 one-hour daily sessions of cognitive remediation (Brain Fitness Program) over eight weeks.
Other Name: Brain Fitness Program
Placebo Comparator: Placebo
Participants will receive placebo weekly, one hour before the first cognitive remediation session of the week, for eight weeks.
Drug: Placebo
Placebo by mouth one hour before first cognitive remediation session each week for eight weeks.
Behavioral: Cognitive Remediation
40 one-hour daily sessions of cognitive remediation (Brain Fitness Program) over eight weeks.
Other Name: Brain Fitness Program

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT00963924

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: NCT00963924     History of Changes
Other Study ID Numbers: 2008P002237, 5P50MH060450, 5P50 MH060450, DATR A3-NSC
Study First Received: August 20, 2009
Results First Received: June 23, 2014
Last Updated: July 31, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
Cognitive Impairment
Neuroplasticity
D-cycloserine
NMDA
Anti-Bacterial Agents
Mental Disorders
Psychotic Disorders
Antitubercular Agents
Schizophrenia and Disorders with Psychotic Features
Schizoaffective Disorder

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

ClinicalTrials.gov processed this record on November 24, 2014