DAAOI-1 Treatment for Treatment-resistant Schizophrenia

Study Overview
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Brief Summary
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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
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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.

Official Title
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DAAOI-1 Treatment for Treatment-resistant Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: DAAOI-1
* Drug: DAAOI-1
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BE 1<br>DAAOI-1 1g | Drug: DAAOI-1<br>* DAAOI-1 1g<br>|
| Experimental: BE 2<br>DAAOI-1 2g | Drug: DAAOI-1<br>* DAAOI-1 2g<br>|
| Placebo Comparator: starch pill<br> | Drug: placebo<br>* starch pill<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The severity of psychiatric symptoms | The severity of psychiatric symptoms will be assessed by: Positive and Negative Syndrome Scale(PANSS) Assessment of Negative symptoms(SANS) Global assessment of function(GAF) Quality of life scale(QOL) | week 0, 2, 4, 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PANSS subscales | score changes | week 0,2,4,6 | 
| Hamilton Depression Rating Scale (HAMD) |  | Week 0,2,4, 6 | 
| Cognitive function | 7 domains of Measurement and Treatment Research to Improve Cognition in Schizophrenia [MATRICS] | week 0, 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, NMDA, DAAOI, Clozapine resistant schizophrenia