D-amino Acid Oxidase Inhibition for NMDA Modulation in Schizophrenia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Total scores of PANSS, SANS, GAF, and QOL
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
DAAOI-1
干预措施: D-amino acid oxidase inhibition (DAAOI-1) (Drug)
placebo
干预措施: placebo (Drug)
结局指标
主要结局
Total scores of PANSS, SANS, GAF, and QOL
时间窗: week 0, 2, 4, 6.
Cognitive function
时间窗: 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
次要结局
- 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)