GlyT-1 Inhibitor Treatment for Refractory Schizophrenia

Phase 2

Completed

• Conditions: Schizophrenia; Treatment Refractory
• Interventions: Drug: Placebo; Drug: GlyT-1 inhibitor-1

• Registration Number: NCT01251055
• Lead Sponsor: China Medical University Hospital

Brief Summary

The etiology of schizophrenia remains unclear In recent one decade, hypofunction of N-methyl-D-aspartate (NMDA) receptor has been implicated in the pathophysiology of schizophrenia. Hence, enhancing NMDA neurotransmission was considered as a new approach for schizophrenia treatment.

To date, refractory schizophrenia (particularly clozapine-resistant) is still a difficult clinical issue. However, the effect of NMDA treatment in refractory schizophrenia is still unknown. Therefore, the primary goal of this study is to investigate the efficacy and safety of NMDA adjuvant therapy in refractory schizophrenia, and to identify the predictors for treatment response to NMDA enhancers.

Detailed Description

The etiology of schizophrenia remains unclear. In recent one decade, hypofunction of N-methyl-D-aspartate (NMDA) receptor has been implicated in the pathophysiology of schizophrenia. Hence, enhancing NMDA neurotransmission was considered as a new approach for schizophrenia treatment. To date, there have been a few pilot studies exploring the efficacy of NMDA enhancers as adjuvant therapy for schizophrenia, for instance, D-serine (an endogenous agonist of the NMDA-glycine site). They were not only well-tolerated but also synergistic in improving positive, negative and cognitive symptoms in those receiving typical and atypical antipsychotics (except clozapine).

Refractory schizophrenia (particularly clozapine-resistant) is still a difficult clinical issue at present. Previous studies revealed that add-on treatment of D-serine or other agonists of NMDA receptor failed to give significant benefits in such patients. The primary goal of this study is to investigate the efficacy and safety of glycine transporter(GlyT)-1 inhibitor adjuvant therapy in refractory schizophrenia, and to identify the predictors for treatment response to NMDA enhancers.

Study Timeline

• Study Start: 2010-04
• Study First Submitted: 2010-11-03
• Study First Submitted QC: 2010-11-30
• Study First Posted: 2010-12-01
• Status Verified: 2013-10
• Primary Completion: 2013-10
• Study Completion: 2013-10
• Last Update Submitted: 2013-10-27
• Last Update Posted: 2013-10-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Fulfill the criteria of schizophrenia according to the Diagnostic and Statistic Manual, fourth edition (DSM-IV).
• Poor response of clozapine treatment: a 12-week treatment of clozapine without satisfactory response: a severity score of Clinical Global Impression Scale(CGI)>=4, a total score of Positive and Negative Syndrome Scale(PANSS)>= 60, and a Scale for the Assessment of Negative Symptoms(SANS)score of >=40. the doses of clozapine remain stable for at least 12 weeks prior to their enrollment in this proposed study,
• Agree to participate in the study and provide informed consent.

Exclusion Criteria

• current substance abuse or history of substance dependence in the past 6 months
• use of depot antipsychotic in the past 6 months
• serious medical or neurological illness
• pregnancy
• inability to follow protocol.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
GlyT-1 inhibitor-1	GlyT-1 inhibitor-1	GlyT-1 inhibitor-1 4000 mg/day

Primary Outcome Measures

Name	Time	Method
The severity of psychiatric symptoms	6 weeks after the trial (The end of the trial)	The severity of psychiatric symptoms will be assessed by: 1. Positive and Negative Syndrome Scale(PANSS); 2. Assessment of Negative symptoms(SANS); 3. Global assessment of function(GAF)

Secondary Outcome Measures

Name	Time	Method
Neurocognitive Function	baseline	The neurocognitive functions will be assessed by: 1. Wisconsin Card Sorting Test (WCST); 2. Wechsler Memory Scale- logical memory
Neurocognitive function	6 weeks after the trial (The end of the trial)	The neurocognitive functions will be assessed by: 1. Wisconsin Card Sorting Test (WCST); 2. Wechsler Memory Scale- logical memory
The severity of psychiatric symptoms	6 weeks after the trial (the end of the trial)	The severity of psychiatric symptoms will be assessed by: 1. Clinical Global Impression(CGI); 2. Subscales of PANSS

Trial Locations

Locations (1)

China Medical University Hospital; 🇨🇳 Taichung, Taiwan