DAAOI-2 add-on 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 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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: DAAOI-2; Drug: placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• 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: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)

Collaborators and Investigators

• Sponsor: China Medical University Hospital
• Collaborators: Ministry of Science and Technology, Taiwan

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: August 10, 2015
• First Submitted That Met QC Criteria: August 23, 2015
• First Posted (Estimate): August 26, 2015

Study Record Updates

• Last Update Posted (Actual): January 30, 2018
• Last Update Submitted That Met QC Criteria: January 29, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Treatment resistant; NMDA; DAAOI
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: NSC-101-2314-B-039-030-MY3