Treatment of N-methyl-D-aspartate (NMDA) Enhancers for Schizophrenia

N-methyl-D-aspartate (NMDA) Enhancers' Benefit to Schizophrenia Treatment

Hypofunction of N-methyl-D-aspartate (NMDA) receptor has been implicated in the pathophysiology of schizophrenia. To date, several reported trials on adjuvant NMDA-enhancing agents, including glycine and sarcosine (a glycine transporter I inhibitor), demonstrated clinical benefits for schizophrenia patients. This project aims to compare the efficacy and safety of sarcosine and combination of sarcosine and BE, as adjunctive therapy for schizophrenia, and to explore the possible synergistic effects of them. Sixty chronic schizophrenic inpatients will be enrolled in the 12-week double-blind, placebo-controlled trial. The participants receive stable antipsychotic regimens concomitant with sarcosine (2 g/d) (N=21), sarcosine(2 g/d) + BE(1 g/d ) (N=21), and placebo(N=21). Measures of clinical efficacy and side-effects were determined every 3 weeks. Measures of cognitive function were determined at the beginning and the end of the study. The efficacies of three groups are compared, and the characteristics of better responders are analyzed.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: sarcosine; Drug: sarcosine+ BE; Drug: placebo

Detailed Description

We will measure clinical efficacy every 3 weeks during the treatment. At the beginning and the end of the trial,We will utilize a battery of tests to assess the effect of the treatment on cognitive functions.The side effect assessments are also performed every 3 weeks. Side effect assessments include Simpson-Angus Rating Scale for extrapyramidal side-effects, Abnormal Involuntary Movement Scale (AIMS) for dyskinesia, and Barnes Akathisia Scale. Systemic side effects are reviewed by applying the Udvalg for Kliniske Undersogelser (UKU) Side-effects Rating Scale. DAAO level, routine laboratory tests, including CBC, biochemistry , urine analysis, and EKG, will be checked at baseline and the end of week 12.

To compare the metabolic syndrome parameters among groups, body mass index, hip size, waist size, blood pressure, fasting blood sugar, triglyceride, and total-cholesterol will be checked at baseline and the end of the study.

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Changhua, Taiwan, 513
    • Changhua Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The participants fulfill the criteria of schizophrenia according to the
• Diagnostic and Statistic Manual, fourth edition (DSM-IV).
• The participants remain stable schizophrenic symptoms and receive stable antipsychotic regimens at last 8 weeks before enrollment.
• The participants agree to participate in the study and provide informed consent.

Exclusion Criteria:

• History of alcohol or substance dependence, history of epilepsy, head trauma or CNS diseases, history of major, untreated medical diseases, mental retardation, pregnancy or lactation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: placebo; placebo,oral, for 12 weeks
Active Comparator: sarcosine	Drug: sarcosine; sarcosine, 2 g/d , oral, for 12 weeks
Active Comparator: sarcosine+ BE	Drug: sarcosine+ BE; sarcosine(2 g/d) + BE (1 g/d ), oral, for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Positive, negative, cognitive symptoms of schizophrenia, laboratory tests.	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
The subscales of PANSS,MATRICS, and serum DAAO levels.	12 weeks

Collaborators and Investigators

• Sponsor: Chang-Hua Hospital
• Collaborators: China Medical University Hospital
• Investigators: Principal Investigator: Chun-yuan Lin, MD, Changhua Hospital; Study Director: Hsien-yuan Lane, MD,PHD, China Medical University Hospital

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: January 12, 2010
• First Submitted That Met QC Criteria: January 12, 2010
• First Posted (Estimate): January 13, 2010

Study Record Updates

• Last Update Posted (Estimate): July 8, 2014
• Last Update Submitted That Met QC Criteria: July 6, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Schizophrenia; cognitive function; N-methyl-D-aspartate receptor
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: DMR98-IR-014; HAC9814 (Other Identifier: Hospital Adminstration Comission, DOH, Taiwan)