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

China Medical University

Status and phase

Completed

Phase 2

Conditions

Schizophrenic Disorders

Psychotic Disorders

Schizophrenias

Psychoses

Treatments

Drug: Sarcosine and D-serine

Study type

Interventional

Funder types

Other

Identifiers

NCT00491569

NSC-94-2314-B-039-026

Details and patient eligibility

About

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.

Full 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.

Enrollment

60 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No 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