GlyT-1 Inhibitor Treatment for Refractory Schizophrenia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hsien-Yuan Lane, China Medical University Hospital
ClinicalTrials.gov Identifier:
NCT01251055
First received: November 3, 2010
Last updated: October 27, 2013
Last verified: October 2013

November 3, 2010
October 27, 2013
April 2010
October 2013   (final data collection date for primary outcome measure)
  • 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)
  • The severity of psychiatric symptoms [ Time Frame: baseline ] [ Designated as safety issue: No ]

    The severity of psychiatric symptoms will be assessed by:

    1. Clilnical Global Impression(CGI)
    2. Positive and Negative Syndrome Scale(PANSS)
    3. Assessment of Negative symptoms(SANS)
  • 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. Clilnical Global Impression(CGI)
    2. Positive and Negative Syndrome Scale(PANSS)
    3. Assessment of Negative symptoms(SANS)
  • 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. Clilnical Global Impression(CGI)
    2. Positive and Negative Syndrome Scale(PANSS)
    3. Assessment of Negative symptoms(SANS)
  • 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. Clilnical Global Impression(CGI)
    2. Positive and Negative Syndrome Scale(PANSS)
    3. Assessment of Negative symptoms(SANS)
Complete list of historical versions of study NCT01251055 on ClinicalTrials.gov Archive Site
  • 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
  • Extrapyramidal Movement [ Time Frame: 2 weeks after trial ] [ Designated as safety issue: Yes ]

    The side effect of extrapyramidal movement will be evaluated by:

    1. Simpson-Angus Rating Scale
    2. abnormal involuntary movement scale(AIMS)
    3. Barnes Akathisia Scale
  • extrapyramidal movement [ Time Frame: 4 weeks after the trial ] [ Designated as safety issue: Yes ]

    The side effect of extrapyramidal movement will be evaluated by:

    1. Simpson-Angus Rating Scale
    2. abnormal involuntary movement scale(AIMS)
    3. Barnes Akathisia Scale
  • extrapyramidal movement [ Time Frame: 6 weeks after the tiral(The end of the trial) ] [ Designated as safety issue: Yes ]

    The side effect of extrapyramidal movement will be evaluated by:

    1. Simpson-Angus Rating Scale
    2. abnormal involuntary movement scale(AIMS)
    3. Barnes Akathisia Scale
  • 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
  • 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
Not Provided
Not Provided
 
GlyT-1 Inhibitor Treatment for Refractory Schizophrenia
GlyT-1 Inhibitor Treatment for Refractory Schizophrenia and Its Effects on NMDA Modulation

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
  • Schizophrenia
  • Treatment Refractory
  • Drug: GlyT-1 inhibitor-1
    GlyT-1 inhibitor-1(500) 4# BID
  • Drug: Placebo
    starch
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
  • Experimental: GlyT-1 inhibitor-1
    GlyT-1 inhibitor-1 4000 mg/day
    Intervention: Drug: GlyT-1 inhibitor-1
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
40
October 2013
October 2013   (final data collection date for primary outcome measure)

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.
Both
18 Years to 55 Years
No
Contact information is only displayed when the study is recruiting subjects
Taiwan
 
NCT01251055
DMR-98-096
No
Hsien-Yuan Lane, China Medical University Hospital
China Medical University Hospital
Not Provided
Principal Investigator: Hsien-Yuan Lane, MD.PhD. Department of Psychiatry, China Medical University Hospital
China Medical University Hospital
October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP