D-amino Acid Oxidase Inhibition (DAAOI-1) add-on Treatment for Chronic Schizophrenia

Psychotic Disorders Clinical Trial

Official title:

D-amino Acid Oxidase Inhibition for NMDA Modulation in Schizophrenia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00960219
• Other study ID #: NSC-97-2314-B-039-006-MY3
• Secondary ID: NSC-97-2314-B-03
• Status: Completed
• Phase: Phase 2
• First received: August 14, 2009
• Last updated: July 7, 2011
• Start date: April 2009
• Est. completion date: July 2011

Study information

• Verified date: July 2011
• Source: China Medical University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Department of Health
• Study type: Interventional

Clinical Trial Summary

Adjuvant N-methyl-D-aspartic acid (NMDA)-enhancing agents, such as GlyT-1 inhibitors and NMDA-glycine site agonists have been demonstrated to be beneficial for chronic schizophrenia patients. The purpose of this study is to evaluate efficacy and safety of add-on treatment of an inhibitor of D-amino acid oxidase (DAAOI), DAAOI-1, in chronically stable schizophrenia patients who have been stabilized with antipsychotics.

Description:

The etiology of schizophrenia remains unclear. Schizophrenia patients reveal positive symptoms, negative symptoms, and cognitive impairments. In addition to dopamine system hyperactivity, hypofunction of N-methyl-D-aspartate (NMDA) receptor plays a role in the pathophysiology of schizophrenia. Consequently, enhancing NMDA receptor neurotransmission has been regarded as a novel treatment approach. To date, several reported trials on 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.

DAAOI-1 is a D-amino acid oxidase (DAAO) inhibitor which can elevate synaptic concentration of D-amino acids. The aim of this project is to examine the efficacy and safety of add-on treatment of DAAOI-1 in chronically stable schizophrenia patients who have been stabilized with antipsychotics.

In the study, 60 schizophrenic patients are recruited into the 6-week trial and randomly assigned into the two groups (1 gm/dDAAOI-1, or placebo) with a double-blind manner. Positive and Negative Syndrome Scale (PANSS), Scales for the Assessment of Negative symptoms (SANS), Global Assessment of Function (GAF), quality of life (QOL), Hamilton Depression rating scale 17(HAM-D 17), Clinical Global Impression(CGI)and side effects are evaluated every two weeks during the trial. Cognitive function ("7 domains of Measurement and Treatment Research to Improve Cognition in Schizophrenia" [MATRICS])are assessed at weeks 0 and 6. The efficacies of two groups are compared.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Are physically healthy and have all laboratory assessments (including urine/blood routine, biochemical tests, and electrocardiograph) within normal limits

• Aged 18-65 year

• Fulfill the criteria of schizophrenia according to the Diagnostic and Statistical Manual, fourth edition (DSM-IV)

• 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 60 on the Positive and Negative Syndrome Scale (PANSS)

• Agree to participate in the study and provide informed consent

Exclusion Criteria:

• DSM-IV diagnosis of substance (including alcohol) abuse or dependence,

• DSM_IV diagnosis of mental retardation

• History of epilepsy, head trauma or CNS diseases

• History of epilepsy, head trauma or CNS diseases

• Pregnancy or lactation

• Inability to follow protocol

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Disease
• Mental Disorders
• Psychoses
• Psychotic Disorders
• Schizophrenia
• Schizophrenias
• Schizophrenic Disorders

Intervention

Drug:
• D-amino acid oxidase inhibition (DAAOI-1)
1g/day(500mg BID), oral, for 6 weeks
• placebo
1# BID, oral, for 6 weeks

Locations

Country	Name	City	State
Taiwan	Department of Psychiatry, China Medical University Hospital	Taichung

Sponsors (1)

Lead Sponsor	Collaborator
China Medical University Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total scores of PANSS, SANS, GAF, and QOL		week 0, 2, 4, 6.	Yes
Primary	Cognitive function	MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia), including:1) speed of processing;(2) sustained attention; 3) working memory, verbal and nonverbal; 4) verbal learning and memory; 5) visual learning and memory; 6) reasoning and problem solving, and 7) social cognition	Week 0, 6	No
Secondary	The subscales of PANSS		week 0,2,4,6	Yes
Secondary	Hamilton Depression rating scale 17(HAM-D 17)		Week 0, 2, 4, 6	No
Secondary	Clinical Global Impression(CGI)		Week 0, 2, 4, 6	No