DAAOI-2 add-on 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 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
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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.

Official Title
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DAAOI-2 add-on Treatment for Treatment-resistant Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: DAAOI-2
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DAAOI-2<br>DAAOI-2: 500-2000mg/d | Drug: DAAOI-2<br>* 500-2000mg/d, oral, for 6 weeks<br>|
| Placebo Comparator: placebo<br> | Drug: placebo<br>* oral, for 6 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive and Negative Syndrome Scale(PANSS) |  | baseline | 
| Positive and Negative Syndrome Scale(PANSS) |  | 2 weeks after the trial | 
| Positive and Negative Syndrome Scale(PANSS) |  | 4 weeks after the trial | 
| Positive and Negative Syndrome Scale(PANSS) |  | 6 weeks after the trial (The end of the trial) | 
| Assessment of Negative symptoms(SANS) |  | baseline | 
| Assessment of Negative symptoms(SANS) |  | 2 weeks after the trial | 
| Assessment of Negative symptoms(SANS) |  | 4 weeks after the trial | 
| Assessment of Negative symptoms(SANS) |  | 6 weeks after the trial (The end of the trial) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PANSS subscales |  | baseline | 
| PANSS subscales |  | 2 weeks after the trial | 
| PANSS subscales |  | 4 weeks after the trial | 
| PANSS subscales |  | 6 weeks after the trial (The end of the trial) | 
| Clinical Global Impression (CGI) |  | baseline | 
| Clinical Global Impression (CGI) |  | 2 weeks after the trial | 
| Clinical Global Impression (CGI) |  | 4 weeks after the trial | 
| Clinical Global Impression (CGI) |  | 6 weeks after the trial (The end of the trial) | 
| Global assessment of function (GAF) |  | baseline | 
| Global assessment of function (GAF) |  | 2 weeks after the trial | 
| Global assessment of function (GAF) |  | 4 weeks after the trial | 
| Global assessment of function (GAF) |  | 6 weeks after the trial (The end of the trial) | 
| Hamilton Depression Rating Scale (HAMD) |  | baseline | 
| Hamilton Depression Rating Scale (HAMD) |  | 2 weeks after the trial | 
| Hamilton Depression Rating Scale (HAMD) |  | 4 weeks after the trial | 
| Hamilton Depression Rating Scale (HAMD) |  | 6 weeks after the trial (The end of the trial) | 
| Quality of life scale (QOL) |  | baseline | 
| Quality of life scale (QOL) |  | 2 weeks after the trial | 
| Quality of life scale (QOL) |  | 4 weeks after the trial | 
| Quality of life scale (QOL) |  | 6 weeks after the trial (The end of the trial) | 
| Measurement and Treatment Research to Improve Cognition in Schizophrenia [MATRICS] | An intergrated score from 7 domains: speed of processing: category fluency, trail making A, and digit symbol - coding from Wechsler adult intelligence scale (WAIS-III); sustained attention: continuous performance test; verbal and nonverbal working memory: backward digit span and spatial span from Wechsler memory scale (WMS-III); verbal learning and memory: word listing from WMS-III; visual learning and memory: visual reproduction from WMS-III; reasoning and problem solving: maze from Wechsler intelligence scale for children (WISC-III); social cognition: the managing emotions branch of Mayer-Salovey-Caruso emotional intelligence test (MSCEIT) | baseline | 
| Measurement and Treatment Research to Improve Cognition in Schizophrenia [MATRICS] | An intergrated score from 7 domains: speed of processing: category fluency, trail making A, and digit symbol - coding from Wechsler adult intelligence scale (WAIS-III); sustained attention: continuous performance test; verbal and nonverbal working memory: backward digit span and spatial span from Wechsler memory scale (WMS-III); verbal learning and memory: word listing from WMS-III; visual learning and memory: visual reproduction from WMS-III; reasoning and problem solving: maze from Wechsler intelligence scale for children (WISC-III); social cognition: the managing emotions branch of Mayer-Salovey-Caruso emotional intelligence test (MSCEIT) | 6 weeks after the trial (The end of the trial) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment resistant, DAAOI, NMDA