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GlyT-1 Inhibitor Treatment for Refractory Schizophrenia

This study is currently recruiting participants.
Verified April 2012 by China Medical University Hospital
Sponsor:
Information provided by (Responsible Party):
Hsien-Yuan Lane, China Medical University Hospital
ClinicalTrials.gov Identifier:
NCT01251055
First received: November 3, 2010
Last updated: April 9, 2012
Last verified: April 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Schizophrenia
Treatment Refractory
 Drug: GlyT-1 inhibitor-1
Drug: Placebo
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: GlyT-1 Inhibitor Treatment for Refractory Schizophrenia and Its Effects on NMDA Modulation

Resource links provided by NLM:

MedlinePlus related topics: Schizophrenia
U.S. FDA Resources

Further study details as provided by China Medical University Hospital:

Primary Outcome Measures:
  • The severity of psychiatric symptoms [ Time Frame: baseline ] [ Designated as safety issue: No ]

    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)

  • The severity of psychiatric symptoms [ Time Frame: 2 weeks after the trial ] [ Designated as safety issue: No ]

    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)

  • The severity of psychiatric symptoms [ Time Frame: 4 weeks after the trial ] [ Designated as safety issue: No ]

    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)

  • The severity of psychiatric symptoms [ Time Frame: 6 weeks after the trial (The end of the trial) ] [ Designated as safety issue: No ]

    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:
  • Neurocognitive Function [ Time Frame: baseline ] [ Designated as safety issue: No ]

    The neurocognitive functions will be assessed by:

    1. Wisconsin Card Sorting Test (WCST)
    2. Wechsler Memory Scale- logical memory

  • Neurocognitive function [ Time Frame: 6 weeks after the trial (The end of the trial) ] [ Designated as safety issue: No ]

    The neurocognitive functions will be assessed by:

    1. Wisconsin Card Sorting Test (WCST)
    2. Wechsler Memory Scale- logical memory

  • The severity of psychiatric symptoms [ Time Frame: baseline ] [ Designated as safety issue: No ]

    The severity of psychiatric symptoms will be assessed by:

    1. Clinical Global Impression(CGI)
    2. Subscales of PANSS

  • The severity of psychiatric symptoms [ Time Frame: 2 weeks after the trial ] [ Designated as safety issue: No ]

    The severity of psychiatric symptoms will be assessed by:

    1. Clinical Global Impression(CGI)
    2. Subscales of PANSS

  • The severity of psychiatric symptoms [ Time Frame: 4 weeks after the trial ] [ Designated as safety issue: No ]

    The severity of psychiatric symptoms will be assessed by:

    1. Clinical Global Impression(CGI)
    2. Subscales of PANSS

  • The severity of psychiatric symptoms [ Time Frame: 6 weeks after the trial (the end of the trial) ] [ Designated as safety issue: No ]

    The severity of psychiatric symptoms will be assessed by:

    1. Clinical Global Impression(CGI)
    2. Subscales of PANSS


Estimated Enrollment: 32
Study Start Date: April 2010
Estimated Study Completion Date: June 2012
Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Placebo
starch
Experimental: GlyT-1 inhibitor-1
GlyT-1 inhibitor-1 4000 mg/day
 Drug: GlyT-1 inhibitor-1
GlyT-1 inhibitor-1(500) 4# BID

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01251055

Contacts
Contact: Hsien-Yuan Lane, MD.PhD. 886-4-22052121 ext 1074 hylane@gmail.com

Locations
Taiwan
China Medical University Hospital Recruiting
Taichung, Taiwan, 400
Contact: Hsien-Yuan Lane, MD.PhD.     886-4-22052121 ext 1074     hylane@gmail.com    
Contact: Yu-Jhen Huang, MD.     886-4-22052121 ext 1074     hyj0514@gmail.com    
Principal Investigator: Hsien-Yuan Lane, MD.PhD.            
Sponsors and Collaborators
China Medical University Hospital
Investigators
Principal Investigator: Hsien-Yuan Lane, MD.PhD. Department of Psychiatry, China Medical University Hospital
Study Director: Guochuan E Tsai, MD, PhD Department of Psychiatry, Harbor-UCLA Medical Center, Torrance, California
  More Information

No publications provided

Responsible Party: Hsien-Yuan Lane, Department of Psychiatry, China Medical University Hospital, China Medical University Hospital
ClinicalTrials.gov Identifier: NCT01251055     History of Changes
Other Study ID Numbers: DMR-98-096
Study First Received: November 3, 2010
Last Updated: April 9, 2012
Health Authority: Taiwan: Institutional Review Board

Keywords provided by China Medical University Hospital:
N-methyl-D-aspartate receptor
glycine transporter
schizophrenia

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders

ClinicalTrials.gov processed this record on June 18, 2013