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

Condition(s) targeted: Schizophrenias; Psychoses; Psychotic Disorders; Schizophrenic Disorders

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

Phase: Phase 2

Status: Completed

Sponsored by: China Medical University Hospital

Official(s) and/or principal investigator(s):
Hsien-Yuan Lane, M.D., Ph.D, Principal Investigator, Affiliation: Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan

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.

Official title: D-amino Acid Oxidase Inhibition for NMDA Modulation in Schizophrenia

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

Primary outcome:

Total scores of PANSS, SANS, GAF, and QOL

Cognitive function

Secondary outcome:

The subscales of PANSS

Hamilton Depression rating scale 17(HAM-D 17)

Clinical Global Impression(CGI)

Detailed 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.

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

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

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

Starting date: April 2009
Last updated: July 7, 2011