Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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WITHDRAWN
PHASE3
INTERVENTIONAL
1998-03-31
2005-11-30
Brief Summary
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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 through the Scale for the Assessment of Negative Symptoms, Positive symptoms will be monitored through the Positive and Negative Syndrome Scale, and additionally subjects will complete the Brief Psychiatric Rating Scale and the Global Assessment Scale.
An individual may be eligible for this study if he/she is 18 to 65 years old and has been diagnosed with schizophrenia.
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Detailed Description
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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 N-methyl-D-aspartate (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.
This study proposes to administer a fixed-dose of D-cycloserine, glycine, or placebo 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.
The study was ultimately suspended before participants were enrolled, due to definitive findings indicating that pairing treatment of D-cycloserine with Clozapine resulted in worsening of negative symptoms.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
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Glycine
The patients will undergo a 2 week single blind placebo lead in followed by an 8 week randomly assigned double blind treatment phase with 30 grams of glycine in 7 ounces of lemonade twice a day in addition to clozapine treatment.
Glycine
Clozapine
Placebo
The patients will undergo a 2 week single blind placebo lead in followed by an 8 week randomly assigned double blind treatment phase with 30 grams of placebo powder in 7 ounces of lemonade twice a day in addition to clozapine treatment.
Clozapine
Placebo
D-Cycloserine
The patients will undergo a 2 week single blind placebo lead in followed by an 8 week randomly assigned double blind treatment phase with D-cycloserine in addition to clozapine treatment.
D-cycloserine
Clozapine
Interventions
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D-cycloserine
Glycine
Clozapine
Placebo
Eligibility Criteria
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Inclusion Criteria
* Score of 27 or greater on the Scale for the Assessment of Negative Symptoms (SANS)
* Treatment with stable dose of clozapine for at least 4 weeks
* Between 18 and 65 years old
Exclusion Criteria
* Current major depressive episode
* Current substance abuse diagnosis
18 Years
65 Years
ALL
No
Sponsors
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Massachusetts General Hospital
OTHER
Responsible Party
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Donald C. Goff, MD
Director of the Schizophrenia Clinical and Research Program
Principal Investigators
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Donald Goff, MD
Role: PRINCIPAL_INVESTIGATOR
Locations
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Freedom Trail Clinic
Boston, Massachusetts, United States
Countries
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References
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Koc-Vural U, Kerimova-Kose L, Kiremitci A. Long-term clinical comparison of a resin-based composite and resin modified glass ionomer in the treatment of cervical caries lesions. Odontology. 2025 Jan;113(1):404-415. doi: 10.1007/s10266-024-00958-6. Epub 2024 Jun 5.
Other Identifiers
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DSIR
Identifier Type: -
Identifier Source: secondary_id
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