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

This study has been completed.
Sponsor:
Information provided by:
China Medical University Hospital
ClinicalTrials.gov Identifier:
NCT00960219
First received: August 14, 2009
Last updated: July 7, 2011
Last verified: July 2011

August 14, 2009
July 7, 2011
April 2009
July 2011   (final data collection date for primary outcome measure)
  • Total scores of PANSS, SANS, GAF, and QOL [ Time Frame: week 0, 2, 4, 6. ] [ Designated as safety issue: Yes ]
  • Cognitive function [ Time Frame: Week 0, 6 ] [ Designated as safety issue: No ]
    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
Same as current
Complete list of historical versions of study NCT00960219 on ClinicalTrials.gov Archive Site
  • The subscales of PANSS [ Time Frame: week 0,2,4,6 ] [ Designated as safety issue: Yes ]
  • Hamilton Depression rating scale 17(HAM-D 17) [ Time Frame: Week 0, 2, 4, 6 ] [ Designated as safety issue: No ]
  • Clinical Global Impression(CGI) [ Time Frame: Week 0, 2, 4, 6 ] [ Designated as safety issue: No ]
The subscales of PANSS [ Time Frame: week 0,2,4,6 ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
D-amino Acid Oxidase Inhibition (DAAOI-1) add-on Treatment for Chronic Schizophrenia
D-amino Acid Oxidase Inhibition for NMDA Modulation in Schizophrenia

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Schizophrenias
  • Psychoses
  • Psychotic Disorders
  • Schizophrenic Disorders
  • Drug: D-amino acid oxidase inhibition (DAAOI-1)
    1g/day(500mg BID), oral, for 6 weeks
    Other Name: DAAOI-1
  • Drug: placebo
    1# BID, oral, for 6 weeks
    Other Name: starch
  • Experimental: DAAOI-1
    Intervention: Drug: D-amino acid oxidase inhibition (DAAOI-1)
  • Placebo Comparator: placebo
    Intervention: Drug: placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
52
July 2011
July 2011   (final data collection date for primary outcome measure)

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
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
Taiwan
 
NCT00960219
NSC-97-2314-B-039-006-MY3, NSC-97-2314-B-039-006-MY3
Yes
Hsien-Yuan Lane, M.D., Ph.D, Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan
China Medical University Hospital
Not Provided
Principal Investigator: Hsien-Yuan Lane, M.D., Ph.D Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan
China Medical University Hospital
July 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP