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Sponsored by: |
National Institute of Mental Health (NIMH) |
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Information provided by: | National Institute of Mental Health (NIMH) |
ClinicalTrials.gov Identifier: | NCT00000371 |
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 | Intervention | Phase |
---|---|---|
Schizophrenia |
Drug: D-cycloserine Drug: Antipsychotic medication |
Phase III |
Study Type: | Interventional |
Study Design: | Treatment, Placebo Control |
Study Start Date: | August 1996 |
Estimated Study Completion Date: | April 1999 |
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.
Ages Eligible for Study: | 18 Years to 65 Years |
Genders Eligible for Study: | Both |
Inclusion Criteria:
-
Patients must have:
Schizophrenia with prominent, primary negative symptoms.
Study ID Numbers: | MH54245 |
Study First Received: | November 2, 1999 |
Last Updated: | November 14, 2005 |
ClinicalTrials.gov Identifier: | NCT00000371 |
Health Authority: | United States: Federal Government |
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 |
Cycloserine Schizophrenia Dopamine Mental Disorders Quality of Life |
Psychotic Disorders N-Methylaspartate Serotonin Schizophrenia and Disorders with Psychotic Features |
Antimetabolites Anti-Bacterial Agents Anti-Infective Agents Molecular Mechanisms of Pharmacological Action Therapeutic Uses |
Anti-Infective Agents, Urinary Antitubercular Agents Renal Agents Pharmacologic Actions Antibiotics, Antitubercular |