- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00000372
Glycine and D-Cycloserine in Schizophrenia
A Placebo Controlled Trial of Glycine Added to Clozapine in Schizophrenia
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 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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
To determine if glycine produces improvement in negative symptoms and D-cycloserine produces worsening in symptoms compared to placebo, patients will undergo a double blind study of d-cycloserine and glycine treatment added to clozapine.
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.
Study Type
Phase
- Phase 3
Contacts and Locations
Study Locations
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Massachusetts
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Boston, Massachusetts, United States, 02114
- Freedom Trail Clinic
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Diagnosis of Schizophrenia
- 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:
- No other antipsychotic medications in oral for for at least 3 months or in depot form for 6 months
- Current major depressive episode
- Current substance abuse diagnosis
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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.
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Placebo Comparator: 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.
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Experimental: 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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change in SANS Total Score from Baseline to Week 8
Time Frame: Baseline, Week 8
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Baseline, Week 8
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change in Positive and Negative Syndrome Score from Baseline to Week 8
Time Frame: Baseline, Week 8
|
Baseline, Week 8
|
Other Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change in Brief Psychotic Rating Scale from Baseline to Week 8
Time Frame: Baseline, Week 8
|
Baseline, Week 8
|
Change in Global Assessment Scale from Baseline to Week 8
Time Frame: Baseline, Week 8
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Baseline, Week 8
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Donald Goff, MD
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Schizophrenia Spectrum and Other Psychotic Disorders
- Schizophrenia
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Central Nervous System Depressants
- Antimetabolites
- Anti-Bacterial Agents
- Antipsychotic Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Serotonin Agents
- Serotonin Antagonists
- GABA Agents
- Antitubercular Agents
- Antibiotics, Antitubercular
- Anti-Infective Agents, Urinary
- Renal Agents
- GABA Antagonists
- Glycine Agents
- Cycloserine
- Clozapine
- Glycine
Other Study ID Numbers
- R01MH057708-02 (U.S. NIH Grant/Contract)
- DSIR
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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