DAAOI-1 Treatment for Treatment-resistant Schizophrenia

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: DAAOI-1; Drug: DAAOI-1; Drug: placebo

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 Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Taichung, Taiwan
    • Department of Psychiatry, China Medical University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BE 1; DAAOI-1 1g	Drug: DAAOI-1; DAAOI-1 1g; Drug: DAAOI-1; DAAOI-1 2g
Experimental: BE 2; DAAOI-1 2g	Drug: DAAOI-1; DAAOI-1 1g; Drug: DAAOI-1; DAAOI-1 2g
Placebo Comparator: starch pill	Drug: placebo; starch pill

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: China Medical University Hospital
• Collaborators: Department of Health, Executive Yuan, R.O.C. (Taiwan)

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: July 7, 2011
• First Submitted That Met QC Criteria: July 8, 2011
• First Posted (Estimate): July 11, 2011

Study Record Updates

• Last Update Posted (Estimate): March 31, 2016
• Last Update Submitted That Met QC Criteria: March 29, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Schizophrenia; NMDA; DAAOI; Clozapine resistant schizophrenia
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: DOH99-TD-I-111-TM001