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

China Medical University

Status and phase

Completed

Phase 2

Conditions

Schizophrenic Disorders

Psychotic Disorders

Schizophrenias

Psychoses

Treatments

Drug: placebo

Drug: D-amino acid oxidase inhibition (DAAOI-1)

Study type

Interventional

Funder types

Other

Identifiers

NCT00960219

NSC-97-2314-B-039-006-MY3

Details and patient eligibility

About

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.

Full 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.

Enrollment

52 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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