Clinical trial NCT01251055: GlyT-1 Inhibitor Treatment for Refractory Schizophrenia
Official title: GlyT-1 Inhibitor Treatment for Refractory Schizophrenia and Its Effects on NMDA Modulation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenia
Treatment Refractory
Keywords: N-methyl-D-aspartate receptor
glycine transporter
schizophrenia
Lead sponsor: China Medical University Hospital
Sponsor class: OTHER
First posted: 2010-12-01
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: The severity of psychiatric symptoms
timeFrame: baseline
measure: The severity of psychiatric symptoms
timeFrame: 2 weeks after the trial
measure: The severity of psychiatric symptoms
timeFrame: 4 weeks after the trial
measure: The severity of psychiatric symptoms
timeFrame: 6 weeks after the trial (The end of the trial)
Secondary outcomes:
measure: Neurocognitive Function
timeFrame: baseline
measure: Neurocognitive function
timeFrame: 6 weeks after the trial (The end of the trial)
measure: The severity of psychiatric symptoms
timeFrame: baseline
measure: The severity of psychiatric symptoms
timeFrame: 2 weeks after the trial
measure: The severity of psychiatric symptoms
timeFrame: 4 weeks after the trial
measure: The severity of psychiatric symptoms
timeFrame: 6 weeks after the trial (the end of the trial)
Other outcomes:
Locations:
city: Taichung
country: Taiwan
facility: China Medical University Hospital
Study officials:
affiliation: Department of Psychiatry, China Medical University Hospital
name: Hsien-Yuan Lane, MD.PhD.
role: PRINCIPAL_INVESTIGATOR
References: