Schizophrenia
Conditions
Keywords
Treatment resistant, DAAOI, NMDA
Brief summary
Pharmacotherapy for schizophrenia has limitations such as residual positive and negative symptoms, cognitive deficits and intolerable side effects. Refractory schizophrenia is still a difficult clinical issue at present. According to the N-methyl-D-aspartate (NMDA) hypothesis, adjuvant NMDA-enhancing agents may have therapeutic benefit. DAAOI-2, a D-amino acid oxidase (DAAO) inhibitor, is a NMDA-enhancing agent. The aim of this project is to examine the effectiveness and safety of DAAOI-2 add-on treatment for treatment-resistant schizophrenia patients in a randomized, double-blind, placebo-controlled trial.
Detailed description
Pharmacotherapy for schizophrenia has limitations such as residual positive and negative symptoms, cognitive deficits and intolerable side effects. Refractory schizophrenia is still a difficult clinical issue at present. According to the N-methyl-D-aspartate (NMDA) hypothesis, many clinical trials on NMDA-enhancing agents were studied. Adjuvant NMDA-enhancing agents, including glycine, D-amino acids such as D-serine, and sarcosine (a glycine transporter I inhibitor), revealed beneficial but limited efficacy for positive and negative symptoms. The aim of this project is to examine the effectiveness and safety of DAAOI-2 add-on treatment for treatment resistant schizophrenia patients in a randomized, double-blind, placebo - controlled trial.
Interventions
DRUGDAAOI-2
500-2000mg/d, oral, for 6 weeks
DRUGplacebo
oral, for 6 weeks
Sponsors
Ministry of Science and Technology, Taiwan
China Medical University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Fulfill the DSM-IV criteria of schizophrenia * Treatment resistant: No satisfactory response to at least two kinds of antipsychotics * Remain symptomatic but without clinically significant fluctuation and the antipsychotic doses are unchanged for at least 3 months * Have a minimum baseline total score of 70 on the Positive and Negative Syndrome Scale (PANSS) * Agree to participate in the study and provide informed consent
Exclusion criteria
* Meet DSM-IV criteria of substance (including alcohol) abuse or dependence * Meet DSM-IV criteria of mental retardation * Serious medical or neurological illness * Pregnancy or lactation * Inability to follow protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Positive and Negative Syndrome Scale(PANSS) | baseline |
| Assessment of Negative symptoms(SANS) | baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Global assessment of function (GAF) | baseline | — |
| Hamilton Depression Rating Scale (HAMD) | baseline | — |
| PANSS subscales | baseline | — |
| Measurement and Treatment Research to Improve Cognition in Schizophrenia [MATRICS] | baseline | An intergrated score from 7 domains: 1. speed of processing: category fluency, trail making A, and digit symbol - coding from Wechsler adult intelligence scale (WAIS-III); 2. sustained attention: continuous performance test; 3. verbal and nonverbal working memory: backward digit span and spatial span from Wechsler memory scale (WMS-III); 4. verbal learning and memory: word listing from WMS-III; 5. visual learning and memory: visual reproduction from WMS-III; 6. reasoning and problem solving: maze from Wechsler intelligence scale for children (WISC-III); 7. social cognition: the managing emotions branch of Mayer-Salovey-Caruso emotional intelligence test (MSCEIT) |
| Quality of life scale (QOL) | baseline | — |
| Clinical Global Impression (CGI) | baseline | — |
Countries
Taiwan
Outcome results
None listed