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

August 20, 2009
July 31, 2014
August 2009
May 2011   (final data collection date for primary outcome measure)
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.
Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) [ Time Frame: Weeks 0 and 8, and Month 6 after cognitive remediation completion ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00963924 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Positive and Negative Syndrome Scale (PANSS) [ Time Frame: Weeks 0, 4 and 8, and Month 6 after cognitive remediation completion ] [ Designated as safety issue: No ]
  • Scale for Assessment of Negative Symptoms (SANS) [ Time Frame: Weeks 0, 4 and 8, and Month 6 after cognitive remediation completion ] [ Designated as safety issue: No ]
  • Global Assessment Scale (GAS) [ Time Frame: Weeks 0, 4 and 8, and Month 6 after cogntive remediation completion ] [ Designated as safety issue: No ]
  • Heinrich Quality of Life Scale (QoL) [ Time Frame: Weeks 0, 4 and 8, and Month 6 after cognitive remediation completion ] [ Designated as safety issue: No ]
  • Calgary Depression Scale for Schizophrenia (CDSS) [ Time Frame: Weeks 0, 4 and 8, and Month 6 after cognitive remediation completion ] [ Designated as safety issue: No ]
  • Clinical Global Impression (CGI) [ Time Frame: Weeks 0 and 8, and Month 6 after cogntive remediation completion ] [ Designated as safety issue: No ]
  • Side Effects Checklist (SEC) [ Time Frame: Weeks 0 - 8, and Month 6 after cogntive remediation completion ] [ Designated as safety issue: Yes ]
  • Brain Fitness Program Processing Speed Assessment [ Time Frame: Weeks 0, 1, 2, 4 and 8 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
D-cycloserine Augmentation of Cognitive Remediation in Schizophrenia
A Placebo-controlled Trial of D-cycloserine Augmentation of Cognitive Remediation in Schizophrenia

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.

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.
Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Schizophrenia
  • Drug: D-cycloserine
    50 mg by mouth one hour before first cognitive remediation session each week for eight weeks.
    Other Name: Cycloserine
  • 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
  • Experimental: D-cycloserine
    Participants will receive D-cycloserine weekly, one hour before the first cognitive remediation session of the week, for eight weeks.
    Interventions:
    • Drug: D-cycloserine
    • Behavioral: Cognitive Remediation
  • Placebo Comparator: Placebo
    Participants will receive placebo weekly, one hour before the first cognitive remediation session of the week, for eight weeks.
    Interventions:
    • Drug: Placebo
    • Behavioral: Cognitive Remediation
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. PubMed PMID: 24485587. .

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
54
June 2011
May 2011   (final data collection date for primary outcome measure)

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.
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00963924
2008P002237, 5P50MH060450, 5P50 MH060450, DATR A3-NSC
No
Donald C. Goff, MD, Massachusetts General Hospital
Massachusetts General Hospital
National Institute of Mental Health (NIMH)
Principal Investigator: Donald C. Goff, M.D. Massachusetts General Hospital
Massachusetts General Hospital
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP