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

NCT ID: NCT00960219

Last Updated: 2011-07-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-04-30
• Study Completion Date: 2011-07-31

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.

Conditions

Schizophrenias; Psychoses; Psychotic Disorders; Schizophrenic Disorders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

DAAOI-1

Group Type: EXPERIMENTAL

D-amino acid oxidase inhibition (DAAOI-1)

Intervention Type: DRUG

1g/day(500mg BID), oral, for 6 weeks

placebo

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

1# BID, oral, for 6 weeks

Interventions

D-amino acid oxidase inhibition (DAAOI-1)

1g/day(500mg BID), oral, for 6 weeks

Intervention Type: DRUG

placebo

1# BID, oral, for 6 weeks

Intervention Type: DRUG

Other Intervention Names

DAAOI-1; starch

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

China Medical University Hospital

OTHER

Sponsor Role: lead

Responsible Party

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

Principal Investigators

Hsien-Yuan Lane, M.D., Ph.D

Role: PRINCIPAL_INVESTIGATOR

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

Locations

Department of Psychiatry, China Medical University Hospital

Taichung, , Taiwan

Countries

Taiwan

References

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.

Reference Type: DERIVED

PMID: 24089054 (View on PubMed)

Other Identifiers

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

Identifier Type: -

Identifier Source: secondary_id

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

Identifier Type: -

Identifier Source: org_study_id