Schizophrenia, Treatment Refractory
Conditions
Keywords
N-methyl-D-aspartate receptor, glycine transporter, schizophrenia
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.
Interventions
DRUGGlyT-1 inhibitor-1
GlyT-1 inhibitor-1(500) 4# BID
DRUGPlacebo
starch
Sponsors
China Medical University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The severity of psychiatric symptoms | baseline | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | baseline | The severity of psychiatric symptoms will be assessed by: 1. Clinical Global Impression(CGI) 2. Subscales of PANSS |
Countries
Taiwan
Outcome results
None listed