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

Psychotic Disorders Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00491569
• Other study ID #: NSC-94-2314-B-039-026
• Status: Completed
• Phase: Phase 2
• First received: June 24, 2007
• Last updated: June 24, 2007
• Start date: January 2005
• Est. completion date: December 2006

Study information

• Verified date: June 2007
• Source: China Medical University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: National Science Council
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: December 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Disease
• Mental Disorders
• Psychoses
• Psychotic Disorders
• Schizophrenia
• Schizophrenias
• Schizophrenic Disorders

Intervention

Drug:
• Sarcosine and D-serine

Locations

Country	Name	City	State
Taiwan	China Medical University Hospital	Taichung

Sponsors (3)

Lead Sponsor	Collaborator
China Medical University Hospital	National Health Research Institutes, Taiwan, National Science Council, Taiwan

Country where clinical trial is conducted

Taiwan, 

References & Publications (1)

Lane HY, Chang YC, Liu YC, Chiu CC, Tsai GE. Sarcosine or D-serine add-on treatment for acute exacerbation of schizophrenia: a randomized, double-blind, placebo-controlled study. Arch Gen Psychiatry. 2005 Nov;62(11):1196-204. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total scores of Positive and Negative Syndrome Scale (PANSS) and Quality of Life (QOL)		6 weeks
Secondary	Subscales of PANSS		6 weeks