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

Study Description

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Brief Summary:

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 or disease	Intervention/treatment	Phase
Schizophrenia	Drug: d-cycloserine	Phase 4

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	38 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Effects of Weekly Dosing of D-cycloserine on Cognitive Function in Individuals
Study Start Date :	July 2004
Actual Primary Completion Date :	April 2007
Actual Study Completion Date :	April 2007

Arms and Interventions

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Arm	Intervention/treatment
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

Outcome Measures

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Primary Outcome Measures :

1. Main Outcome Measure: The Change From Baseline to Week 8 on the SANS [ Time Frame: Baseline score vs. Week 8 ]
   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 :

1. Treatment Effects on the Positive Syndrome Subscale of the PANSS [ Time Frame: Baseline score vs. Week 8 score ]
   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).

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 65 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
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

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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

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Publications of Results:

Goff DC, Cather C, Gottlieb JD, Evins AE, Walsh J, Raeke L, Otto MW, Schoenfeld D, Green MF. Once-weekly D-cycloserine effects on negative symptoms and cognition in schizophrenia: an exploratory study. Schizophr Res. 2008 Dec;106(2-3):320-7. doi: 10.1016/j.schres.2008.08.012. Epub 2008 Sep 16.

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
First Posted:	April 4, 2007
Results First Posted:	August 7, 2014
Last Update Posted:	August 7, 2014
Last Verified:	July 2014

Keywords provided by Donald C. Goff, MD, Massachusetts General Hospital:

schizophrenia; cognition; d-cycloserine; memory

Additional relevant MeSH terms:

Cycloserine; Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Anti-Infective Agents, Urinary; Anti-Infective Agents	Renal Agents; Antibiotics, Antitubercular; Antitubercular Agents; Anti-Bacterial Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action