Schizophrenia
Conditions
Keywords
Schizophrenia, NMDA, DAAOI, Clozapine resistant schizophrenia
Brief summary
Pharmacotherapy for schizophrenia has limitations such as residual positive and negative symptoms, cognitive deficits and intolerable side effects. Refractory schizophrenia (particularly clozapine-resistant) 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-1, a D-amino acid oxidase (DAAO) inhibitor, is a NMDA-enhancing agents. The aim of this project is to examine the effectiveness and safety of DAAOI-1 adjuvant treatment for clozapine-resistant refractory 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 (particularly clozapine-resistant) is still a difficult clinical issue at present. Among schizophrenia patients, around 20-25%are treatment-resistant. 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 (D-serine, D-alanine), and sarcosine (a glycine transporter I inhibitor), revealed beneficial but limited efficacy for positive and negative symptoms. The investigators recently started to study the potential of DAAOI-1, a D-amino acid oxidase (DAAO) inhibitor which can elevate synaptic concentration of D-amino acids. The aims of this project is to examine the effectiveness and safety of DAAOI-1 adjuvant treatment for clozapine-resistant refractory schizophrenia patients in a randomized, double-blind, placebo - controlled trial.
Interventions
DRUGDAAOI-1
DAAOI-1 1g
DRUGplacebo
starch pill
Sponsors
Department of Health, Executive Yuan, R.O.C. (Taiwan)
China Medical University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Fulfilled the DSM-IV criteria of schizophrenia * Poor responder of clozapine: a 12-week treatment without satisfactory response: a minimal total score of 70 on the Positive and Negative Syndrome Scale (PANSS) (Kay 1987), and a minimal total score of 40 on the Scale for the Assessment of Negative Symptoms (SANS) (Andreasen 1983). * Agree to participate in the study and provide informed consent
Exclusion criteria
* Meet DSM-IV criteria of other AXIS I disorder, current substance dependence or mental retardation * Serious medical or neurological illness * Pregnancy or lactation * Use of depot antipsychotic in the past 6 months * Inability to follow protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The severity of psychiatric symptoms | week 0, 2, 4, 6 | 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) 4. Quality of life scale(QOL) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PANSS subscales | week 0,2,4,6 | score changes |
| Hamilton Depression Rating Scale (HAMD) | Week 0,2,4, 6 | — |
| Cognitive function | week 0, 6 | 7 domains of Measurement and Treatment Research to Improve Cognition in Schizophrenia \[MATRICS\] |
Countries
Taiwan
Outcome results
None listed