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

Phase 2
Completed
Conditions
Schizophrenia
Interventions
Drug: placebo
Registration Number
NCT02532686
Lead Sponsor
China Medical University Hospital
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
40
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
DAAOI-2DAAOI-2DAAOI-2: 500-2000mg/d
placeboplacebo-
Primary Outcome Measures
NameTimeMethod
Positive and Negative Syndrome Scale(PANSS)6 weeks after the trial (The end of the trial)
Assessment of Negative symptoms(SANS)6 weeks after the trial (The end of the trial)
Secondary Outcome Measures
NameTimeMethod
Clinical Global Impression (CGI)6 weeks after the trial (The end of the trial)
Quality of life scale (QOL)6 weeks after the trial (The end of the trial)
Hamilton Depression Rating Scale (HAMD)6 weeks after the trial (The end of the trial)
"Measurement and Treatment Research to Improve Cognition in Schizophrenia [MATRICS]6 weeks after the trial (The end of the trial)

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)

Global assessment of function (GAF)6 weeks after the trial (The end of the trial)
PANSS subscales6 weeks after the trial (The end of the trial)

Trial Locations

Locations (1)

Department of Psychiatry, China Medical University Hospital

🇨🇳

Taichung, Taiwan

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