Psychoses, Psychotic Disorders, Schizophrenias, Schizophrenic Disorders
Conditions
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.
Interventions
DRUGD-amino acid oxidase inhibition (DAAOI-1)
1g/day(500mg BID), oral, for 6 weeks
DRUGplacebo
1# BID, oral, for 6 weeks
Sponsors
China Medical University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total scores of PANSS, SANS, GAF, and QOL | week 0, 2, 4, 6. | — |
| Cognitive function | Week 0, 6 | 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
| Measure | Time frame |
|---|---|
| The subscales of PANSS | week 0,2,4,6 |
| Hamilton Depression rating scale 17(HAM-D 17) | Week 0, 2, 4, 6 |
| Clinical Global Impression(CGI) | Week 0, 2, 4, 6 |
Countries
Taiwan
Outcome results
None listed