Suspended

A Placebo Controlled Trial of Glycine Added to Clozapine in Schizophrenia

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What is being tested

Glycine

+ Clozapine

+ Clozapine

Drug
Who is being recruted

Mental Disorders

+ Schizophrenia Spectrum and Other Psychotic Disorders

+ Schizophrenia

From 18 to 65 Years
+7 Eligibility Criteria
See all eligibility criteria
How is the trial designed

Treatment Study

Placebo-ControlledPhase 3
Interventional
Study Start: March 1998
See protocol details

Summary

Principal SponsorMassachusetts General Hospital
Last updated: June 12, 2014
Sourced from a government-validated database.Claim as a partner

Study start date: March 1, 1998

Actual date on which the first participant was enrolled.

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.

NCT00000372
Principal SponsorMassachusetts General Hospital
Last updated: June 12, 2014
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Treatment Study

These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria

Any sex

Biological sex of participants that are eligible to enroll.

From 18 to 65 Years

Range of ages for which participants are eligible to join.

Healthy volunteers not allowed

If individuals who are healthy and do not have the condition being studied can participate.

Conditions

Pathology

Mental DisordersSchizophrenia Spectrum and Other Psychotic DisordersSchizophrenia

Criteria

4 inclusion criteria required to participate
Between 18 and 65 years old
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
3 exclusion criteria prevent from participating
Current major depressive episode
Current substance abuse diagnosis
No other antipsychotic medications in oral for for at least 3 months or in depot form for 6 months

Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives

3 intervention groups are designated in this study

33.333% chance of being blinded to the placebo group

Treatment Groups

Group I

Experimental
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.

Group II

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.

Group III

Experimental
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.

Study Objectives

Primary Objectives

Secondary Objectives

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.

This study has 1 location

Freedom Trail Clinic

Boston, United StatesOpen Freedom Trail Clinic in Google Maps
SuspendedOne Study Center