GlyT-1 Inhibitor Treatment for Refractory Schizophrenia

Schizophrenia Clinical Trial

Official title:

GlyT-1 Inhibitor Treatment for Refractory Schizophrenia and Its Effects on NMDA Modulation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01251055
• Other study ID #: DMR-98-096
• Status: Completed
• Phase: Phase 2
• First received: November 3, 2010
• Last updated: October 27, 2013
• Start date: April 2010
• Est. completion date: October 2013

Study information

• Verified date: October 2013
• Source: China Medical University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: October 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Schizophrenia
• Treatment Refractory

Intervention

Drug:
• GlyT-1 inhibitor-1
GlyT-1 inhibitor-1(500) 4# BID
• Placebo
starch

Locations

Country	Name	City	State
Taiwan	China Medical University Hospital	Taichung

Sponsors (1)

Lead Sponsor	Collaborator
China Medical University Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The severity of psychiatric symptoms	The severity of psychiatric symptoms will be assessed by: Positive and Negative Syndrome Scale(PANSS); Assessment of Negative symptoms(SANS); Global assessment of function(GAF)	baseline	No
Primary	The severity of psychiatric symptoms	The severity of psychiatric symptoms will be assessed by: Positive and Negative Syndrome Scale(PANSS); Assessment of Negative symptoms(SANS); Global assessment of function(GAF)	2 weeks after the trial	No
Primary	The severity of psychiatric symptoms	The severity of psychiatric symptoms will be assessed by: Positive and Negative Syndrome Scale(PANSS); Assessment of Negative symptoms(SANS); Global assessment of function(GAF)	4 weeks after the trial	No
Primary	The severity of psychiatric symptoms	The severity of psychiatric symptoms will be assessed by: Positive and Negative Syndrome Scale(PANSS); Assessment of Negative symptoms(SANS); Global assessment of function(GAF)	6 weeks after the trial (The end of the trial)	No
Secondary	Neurocognitive Function	The neurocognitive functions will be assessed by: Wisconsin Card Sorting Test (WCST); Wechsler Memory Scale- logical memory	baseline	No
Secondary	Neurocognitive function	The neurocognitive functions will be assessed by: Wisconsin Card Sorting Test (WCST); Wechsler Memory Scale- logical memory	6 weeks after the trial (The end of the trial)	No
Secondary	The severity of psychiatric symptoms	The severity of psychiatric symptoms will be assessed by: Clinical Global Impression(CGI); Subscales of PANSS	baseline	No
Secondary	The severity of psychiatric symptoms	The severity of psychiatric symptoms will be assessed by: Clinical Global Impression(CGI); Subscales of PANSS	2 weeks after the trial	No
Secondary	The severity of psychiatric symptoms	The severity of psychiatric symptoms will be assessed by: Clinical Global Impression(CGI); Subscales of PANSS	4 weeks after the trial	No
Secondary	The severity of psychiatric symptoms	The severity of psychiatric symptoms will be assessed by: Clinical Global Impression(CGI); Subscales of PANSS	6 weeks after the trial (the end of the trial)	No