Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Trial of D-Cycloserine in Schizophrenia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00000371
Recruitment Status : Completed
First Posted : November 3, 1999
Results First Posted : September 10, 2014
Last Update Posted : September 10, 2014
Sponsor:
Information provided by (Responsible Party):
Donald C. Goff, MD, Massachusetts General Hospital

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:

To characterize further the effects of D-cycloserine augmentation of antipsychotic treatment on negative symptoms, performance on neurocognitive tasks, and on markers for glutamatergic, dopaminergic and serotonergic function in serum and cerebrospinal fluid. To determine if negative symptoms and cognitive function improve over time, if these improvements meaningfully impact quality of life factors, if they correlate with markers of neuronal function, and if subpopulations can be identified according to response.

Dysfunction of glutamatergic neuronal systems has recently been implicated in the pathophysiology of schizophrenia based on the finding that non-competitive inhibitors of the NMDA receptor can reproduce in normals the positive symptoms, negative symptoms, and cognitive deficits of schizophrenia. Furthermore, glutamatergic dysfunction may alter forebrain dopaminergic neuronal activity, a system central to the antipsychotic action of typical neuroleptics. It is believed that enhancing NMDA receptor function by systemic treatment with D-cycloserine, a partial agonist at the glycine modulatory site of the NMDA receptor, will reduce symptoms in schizophrenia.

Sixty schizophrenic outpatients with prominent, primary negative symptoms are treated with antipsychotic medication and are randomly assigned to D-cycloserine or placebo for a 6-month, fixed-dose trial. The primary outcome measure is the total score on the Scale for Assessment of Negative Symptoms (SANS). A neuropsychological battery, which emphasizes tests sensitive to prefrontal cortical function, is administered. Blood is obtained at several time points and CSF is obtained at Week 8 for assay of concentrations of D-cycloserine, glutamate, HVA, and 5HIAA.


Condition or disease Intervention/treatment Phase
Schizophrenia Drug: D-cycloserine Drug: Placebo Phase 3

Detailed Description:

To characterize further the effects of D-cycloserine augmentation of antipsychotic treatment on negative symptoms, performance on neurocognitive tasks, and on markers for glutamatergic, dopaminergic, and serotonergic function in serum and cerebrospinal fluid. To determine if negative symptoms and cognitive function improve over time, if these improvements meaningfully impact quality of life factors, if they correlate with markers of neuronal function, and if subpopulations can be identified according to response.

Dysfunction of glutamatergic neuronal systems has recently been implicated in the pathophysiology of schizophrenia based on the finding that non-competitive inhibitors of the NMDA receptor can reproduce in normals the positive symptoms, negative symptoms and cognitive deficits of schizophrenia. Furthermore, glutamatergic dysfunction may alter forebrain dopaminergic neuronal activity, a system central to the antipsychotic action of typical neuroleptics. It is believed that enhancing NMDA receptor function by systemic treatment with D-cycloserine, a partial agonist at the glycine modulatory site of the NMDA receptor, will reduce symptoms in schizophrenia.

Sixty schizophrenic outpatients with prominent, primary negative symptoms are treated with antipsychotic medication and are randomly assigned to D-cycloserine or placebo for a 6-month, fixed-dose trial. The primary outcome measure is the total score on the Scale for Assessment of Negative Symptoms (SANS). A neuropsychological battery, which emphasizes tests sensitive to prefrontal cortical function, is administered. Blood is obtained at several time points and CSF is obtained at Week 8 for assay of concentrations of D-cycloserine, glutamate, HVA, and 5HIAA.


Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Six Month, Placebo-Controlled Trial of D-Cycloserine Co-Administered With Conventional Antipsychotics in Schizophrenia Patients
Study Start Date : August 1996
Actual Primary Completion Date : April 2002
Actual Study Completion Date : April 2002

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia
Drug Information available for: Cycloserine

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: D-Cycloserine
Subjects were given 50 mg/day of D-Cycloserine for 24 weeks
 Drug: D-cycloserine
50 mg/daily by mouth
Other Name: Cycloserine
Placebo Comparator: Placebo
Participants were given 50 mg/day of Placebo for 24 weeks.
 Drug: Placebo
50 mg/day of placebo by mouth


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Scale for the Assessment of Negative Symptoms (SANS) [ Time Frame: Baseline, Week 4, Week 8 ]
    The slope of SANS total score from baseline to week 8 in the treatment and placebo groups 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 slopes were obtained by plotting the group SANS total score mean for treatment vs. placebo on Baseline, Week 4, and Week 8 and performing a random slopes model.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of Schizophrenia as per DSM IV criteria
  • Have been treated for at least 6 months with any conventional neuroleptic
  • Have prominent negative symptoms as defined by a total score of 40 or greater on the scale for the assessment of negative symptoms (SANS)

Exclusion Criteria:

  • Active alcohol or drug abuse
  • Unstable Medical Illness, seizure disorder, or other serious neurological disorder
  • Pregnant or Nursing
  • Unable to complete a cognitive battery
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00000371


Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Layout table for investigator information
Principal Investigator: Donald Goff, MD
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications of Results:

Layout table for additonal information
Responsible Party: Donald C. Goff, MD, Director of the Schizophrenia Clinical and Research Program, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00000371     History of Changes
Other Study ID Numbers: R01MH054245-01A2 ( U.S. NIH Grant/Contract )
First Posted: November 3, 1999    Key Record Dates
Results First Posted: September 10, 2014
Last Update Posted: September 10, 2014
Last Verified: September 2014
Keywords provided by Donald C. Goff, MD, Massachusetts General Hospital:
Adult
Cognition
Cycloserine
Dopamine
Female
Glutamic Acid
Human
Male
Receptors, N-Methyl-D-Aspartate
Schizophrenia
 Serotonin
Quality of Life
Cycloserine -- *therapeutic use
Dopamine -- blood
Dopamine -- cerebrospinal fluid
Glutamic Acid -- blood
Glutamic Acid -- cerebrospinal fluid
Serotonin -- blood
Serotonin -- cerebrospinal fluid
Additional relevant MeSH terms:
Layout table for MeSH terms
Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Cycloserine
Dopamine
Serotonin
Cardiotonic Agents
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Dopamine Agents
 Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Protective Agents
Serotonin Receptor Agonists
Serotonin Agents
Anti-Infective Agents, Urinary
Anti-Infective Agents
Renal Agents
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Antimetabolites