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

Sponsor

China Medical University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT00491569

Collaborator

National Science Council, Taiwan (Other), National Health Research Institutes, Taiwan (Other)

Enrollment

Location

Duration (Months)

2.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenias Psychoses Psychotic Disorders Schizophrenic Disorders	Drug: Sarcosine and D-serine	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jan 1, 2005

Actual Study Completion Date :

Dec 1, 2006

Outcome Measures

Primary Outcome Measures

Total scores of Positive and Negative Syndrome Scale (PANSS) and Quality of Life (QOL) [6 weeks]

Secondary Outcome Measures

Subscales of PANSS [6 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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