DAAOI-1 Treatment for Treatment-resistant Schizophrenia

Phase 2

Completed

• Conditions: Schizophrenia
• Interventions: Drug: DAAOI-1; Drug: placebo

• Registration Number: NCT01390376
• 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 (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.

Study Timeline

• Study Start: 2010-09
• Study First Submitted: 2011-07-07
• Study First Submitted QC: 2011-07-08
• Study First Posted: 2011-07-11
• Primary Completion: 2014-09
• Study Completion: 2014-09
• Status Verified: 2016-03
• Last Update Submitted: 2016-03-29
• Last Update Posted: 2016-03-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BE 2	DAAOI-1	DAAOI-1 2g
BE 1	DAAOI-1	DAAOI-1 1g
starch pill	placebo	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Cognitive function	week 0, 6	7 domains of Measurement and Treatment Research to Improve Cognition in Schizophrenia" \[MATRICS\]
PANSS subscales	week 0,2,4,6	score changes
Hamilton Depression Rating Scale (HAMD)	Week 0,2,4, 6

Trial Locations

Locations (1)

Department of Psychiatry, China Medical University Hospital; 🇨🇳 Taichung, Taiwan