Glycine and D-Cycloserine in Schizophrenia
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Purpose
The purpose of this study is to compare the effects of D-cycloserine and glycine for treating negative symptoms (such as loss of interest, loss of energy, loss of warmth, and loss of humor) which occur between phases of positive symptoms (marked by hallucinations, delusions, and thought confusions) in schizophrenics.
Clozapine is currently the most effective treatment for negative symptoms of schizophrenia. Two other drugs, D-cycloserine and glycine, are being investigated as new treatments. D-cycloserine improves negative symptoms when added to some drugs, but may worsen these symptoms when given with clozapine. Glycine also improves negative symptoms and may still be able to improve these symptoms when given with clozapine. This study gives either D-cycloserine or glycine (or an inactive placebo) with clozapine to determine which is the best combination.
Patients will be assigned to 1 of 3 groups. Group 1 will receive D-cycloserine plus clozapine. Group 2 will receive glycine plus clozapine. Group 3 will receive an inactive placebo plus clozapine. Patients will receive these medications for 8 weeks. Negative symptoms of schizophrenia will be monitored, and tests will be done on blood and cerebrospinal fluid (CSF) to measure the body's response to the medications.
An individual may be eligible for this study if he/she:
Is 18 to 65 years old and has been diagnosed with schizophrenia.
| Condition | Intervention | Phase |
|---|---|---|
|
Schizophrenia |
Drug: D-cycloserine Drug: Glycine Drug: Clozapine |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Intervention Model: Parallel Assignment Primary Purpose: Treatment |
| Study Start Date: | March 1998 |
| Estimated Study Completion Date: | February 2001 |
To determine if glycine produces improvement in negative symptoms and D-cycloserine produces worsening in symptoms compared to placebo. To determine whether cerebrospinal fluid concentrations of glycine and other relevant amino acids predict response and measure effects of D-cycloserine and glycine on serum amino acid concentrations.
Clozapine is more effective for negative symptoms of schizophrenia than conventional neuroleptics, but the neurochemical actions contributing to this superior clinical efficacy remain unclear. Recent evidence points to a role for glutamatergic dysregulation in schizophrenia, as well as important differences between conventional agents and clozapine in effects upon glutamatergic systems. D-cycloserine, a partial agonist at the glycine modulatory site of the NMDA receptor, improves negative symptoms when added to conventional agents and worsens negative symptoms when added to clozapine. High-dose glycine also improves negative symptoms and has provided preliminary evidence suggesting that glycine improves negative symptoms when added to clozapine. Serum concentrations of glycine predicted response to both high-dose glycine and D-cycloserine. Both clozapine and D-cycloserine may improve negative symptoms by activation of the glycine modulatory site of the NMDA receptor complex. Because D-cycloserine is a partial agonist, it may act as an antagonist at the glycine site in the presence of clozapine, whereas the full agonist, glycine, would not be expected to worsen negative symptoms in the presence of clozapine.
A fixed-dose of D-cycloserine, glycine, or placebo is added to clozapine in 45 patients with schizophrenia. Because assessments are standardized between studies, results from this study can be compared with results from a previous study of D-cycloserine added to conventional neuroleptic.
Eligibility| Ages Eligible for Study: | 18 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
-
Patients must have:
Schizophrenia.
Contacts and Locations More Information
No publications provided
| ClinicalTrials.gov Identifier: | NCT00000372 History of Changes |
| Other Study ID Numbers: | MH57708, DSIR |
| Study First Received: | November 2, 1999 |
| Last Updated: | December 6, 2005 |
| Health Authority: | United States: Federal Government |
Keywords provided by National Institute of Mental Health (NIMH):
|
Adult Amino Acids Cycloserine Female Glycine Human Male N-Methylaspartate |
Placebos Schizophrenia Amino Acids -- blood Cycloserine -- *therapeutic use Glycine -- *therapeutic use Schizophrenia -- *drug therapy Schizophrenia -- physiopathology |
Additional relevant MeSH terms:
|
Schizophrenia Schizophrenia and Disorders with Psychotic Features Mental Disorders Clozapine Glycine Cycloserine Serotonin Antagonists Serotonin Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Physiological Effects of Drugs Antipsychotic Agents Tranquilizing Agents |
Central Nervous System Depressants Central Nervous System Agents Therapeutic Uses Psychotropic Drugs GABA Antagonists GABA Agents Anti-Infective Agents, Urinary Anti-Infective Agents Renal Agents Antibiotics, Antitubercular Anti-Bacterial Agents Antitubercular Agents Antimetabolites Glycine Agents |
ClinicalTrials.gov processed this record on May 21, 2013