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
  Purpose

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.


Condition Intervention Phase
Schizophrenias
Psychoses
Psychotic Disorders
Schizophrenic Disorders
Drug: D-amino acid oxidase inhibition (DAAOI-1)
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: D-amino Acid Oxidase Inhibition for NMDA Modulation in Schizophrenia

Resource links provided by NLM:


Further study details as provided by China Medical University Hospital:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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 ]

Enrollment: 52
Study Start Date: April 2009
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DAAOI-1 Drug: D-amino acid oxidase inhibition (DAAOI-1)
1g/day(500mg BID), oral, for 6 weeks
Other Name: DAAOI-1
Placebo Comparator: placebo Drug: placebo
1# BID, oral, for 6 weeks
Other Name: starch

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00960219

Locations
Taiwan
Department of Psychiatry, China Medical University Hospital
Taichung, Taiwan
Sponsors and Collaborators
China Medical University Hospital
Investigators
Principal Investigator: Hsien-Yuan Lane, M.D., Ph.D Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan
  More Information

No publications provided by China Medical University Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hsien-Yuan Lane, M.D., Ph.D, Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan
ClinicalTrials.gov Identifier: NCT00960219     History of Changes
Other Study ID Numbers: NSC-97-2314-B-039-006-MY3, NSC-97-2314-B-039-006-MY3
Study First Received: August 14, 2009
Last Updated: July 7, 2011
Health Authority: Taiwan: Department of Health

Additional relevant MeSH terms:
Mental Disorders
Psychotic Disorders
Schizophrenia
Schizophrenia and Disorders with Psychotic Features

ClinicalTrials.gov processed this record on August 20, 2014