Sarcosine or D-Serine Add-on Treatment for Chronic Schizophrenia

Study Overview
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Brief Summary
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Both GlyT-1 inhibitors and NMDA-glycine site agonists have been demonstrated to be beneficial for chronic schizophrenia patients. The purpose of this study is to compare efficacy and safety of add-on treatment of sarcosine, a GlyT-1 inhibitor, and D-serine, an NMDA-glycine site agonist, in chronically stable schizophrenia patients who have been stabilized with antipsychotics.

Detailed Description
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The etiology of schizophrenia remains unclear. Schizophrenia patients reveal positive symptoms, negative symptoms, and cognitive impairments. In addition to dopamine system hyperactivity, hypofunction of N-methyl-D-aspartate (NMDA) receptor plays a role in the pathophysiology of schizophrenia. Consequently, enhancing NMDA receptor neurotransmission has been regarded as a novel treatment approach. To date, there have been several reported trials on NMDA enhancers. Both sarcosine (N-methylglycine, a glycine transporter I inhibitor) and D-serine (a potent NMDA-glycine site agonist) showed therapeutic effects in chronically stable patients. Interestingly, sarcosine appeared more efficacious than D-serine in acutely exacerbated ones when added-on to antipsychotics. Both sarcosine and D-serine yielded excellent safety profiles. It remains unclear whether sarcosine can be also more efficacious than D-serine in the treatment for chronically stable schizophrenia. The aim of this project is to examine the efficacy and safety of add-on treatment of sarcosine vs. D-serine in chronically stable schizophrenia patients who have been stabilized with antipsychotics. In the study, 60-75 schizophrenic patients are recruited into the 6-week trial and randomly assigned into the three groups (2 gm/d sarcosine, 2 gm/d D-serine, or placebo) with a double-blind manner. Clinical manifestation (Positive and Negative Syndrome Scale [PANSS], side effects and quality of life (QOL) are evaluated every two weeks during the trial.. The efficacies of three groups are compared.

Official Title
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NMDA Enhancers in the Treatment of Schizophrenia: Sarcosine vs. D-Serine

Conditions
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Schizophrenias, Psychoses, Psychotic Disorders, Schizophrenic Disorders

Intervention / Treatment
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* Drug: Sarcosine and D-serine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fulfill the criteria of schizophrenia according to the Diagnostic and Statistic Manual, fourth edition (DSM-IV). Agree to participate in the study and provide informed consent. Exclusion Criteria: Meet DSM-IV criteria of major mood disorder, current substance dependence or mental retardation History of epilepsy, head trauma or CNS diseases Major, untreated medical diseases Pregnancy or lactation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Sarcosine and D-serine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total scores of Positive and Negative Syndrome Scale (PANSS) and Quality of Life (QOL) |  | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subscales of PANSS |  | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, sarcosine, D-serine, NMDA