Clinical trial NCT00960219: D-amino Acid Oxidase Inhibition (DAAOI-1) add-on Treatment for Chronic Schizophrenia
Official title: D-amino Acid Oxidase Inhibition for NMDA Modulation in Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenias
Psychoses
Psychotic Disorders
Schizophrenic Disorders
Lead sponsor: China Medical University Hospital
Sponsor class: OTHER
First posted: 2009-08-17
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility 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

Primary outcomes:
measure: Total scores of PANSS, SANS, GAF, and QOL
timeFrame: week 0, 2, 4, 6.
measure: Cognitive function
timeFrame: Week 0, 6
Secondary outcomes:
measure: The subscales of PANSS
timeFrame: week 0,2,4,6
measure: Hamilton Depression rating scale 17(HAM-D 17)
timeFrame: Week 0, 2, 4, 6
measure: Clinical Global Impression(CGI)
timeFrame: Week 0, 2, 4, 6
Other outcomes:
Locations:
city: Taichung
country: Taiwan
facility: Department of Psychiatry, China Medical University Hospital
Study officials:
affiliation: Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan
name: Hsien-Yuan Lane, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lane HY, Lin CH, Green MF, Hellemann G, Huang CC, Chen PW, Tun R, Chang YC, Tsai GE. Add-on treatment of benzoate for schizophrenia: a randomized, double-blind, placebo-controlled trial of D-amino acid oxidase inhibitor. JAMA Psychiatry. 2013 Dec;70(12):1267-75. doi: 10.1001/jamapsychiatry.2013.2159.