GlyT-1 Inhibitor Treatment for Refractory Schizophrenia and Its Effects on NMDA Modulation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- The severity of psychiatric symptoms
研究概览
简要总结
The etiology of schizophrenia remains unclear In recent one decade, hypofunction of N-methyl-D-aspartate (NMDA) receptor has been implicated in the pathophysiology of schizophrenia. Hence, enhancing NMDA neurotransmission was considered as a new approach for schizophrenia treatment.
To date, refractory schizophrenia (particularly clozapine-resistant) is still a difficult clinical issue. However, the effect of NMDA treatment in refractory schizophrenia is still unknown. Therefore, the primary goal of this study is to investigate the efficacy and safety of NMDA adjuvant therapy in refractory schizophrenia, and to identify the predictors for treatment response to NMDA enhancers.
详细描述
The etiology of schizophrenia remains unclear. In recent one decade, hypofunction of N-methyl-D-aspartate (NMDA) receptor has been implicated in the pathophysiology of schizophrenia. Hence, enhancing NMDA neurotransmission was considered as a new approach for schizophrenia treatment. To date, there have been a few pilot studies exploring the efficacy of NMDA enhancers as adjuvant therapy for schizophrenia, for instance, D-serine (an endogenous agonist of the NMDA-glycine site). They were not only well-tolerated but also synergistic in improving positive, negative and cognitive symptoms in those receiving typical and atypical antipsychotics (except clozapine).
Refractory schizophrenia (particularly clozapine-resistant) is still a difficult clinical issue at present. Previous studies revealed that add-on treatment of D-serine or other agonists of NMDA receptor failed to give significant benefits in such patients. The primary goal of this study is to investigate the efficacy and safety of glycine transporter(GlyT)-1 inhibitor adjuvant therapy in refractory schizophrenia, and to identify the predictors for treatment response to NMDA enhancers.
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
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Fulfill the criteria of schizophrenia according to the Diagnostic and Statistic Manual, fourth edition (DSM-IV).
- •Poor response of clozapine treatment: a 12-week treatment of clozapine without satisfactory response: a severity score of Clinical Global Impression Scale(CGI)>=4, a total score of Positive and Negative Syndrome Scale(PANSS)>= 60, and a Scale for the Assessment of Negative Symptoms(SANS)score of >=
- •the doses of clozapine remain stable for at least 12 weeks prior to their enrollment in this proposed study,
- •Agree to participate in the study and provide informed consent.
排除标准
- •current substance abuse or history of substance dependence in the past 6 months
- •use of depot antipsychotic in the past 6 months
- •serious medical or neurological illness
- •pregnancy
- •inability to follow protocol.
研究组 & 干预措施
Placebo
干预措施: Placebo (Drug)
GlyT-1 inhibitor-1
GlyT-1 inhibitor-1 4000 mg/day
干预措施: GlyT-1 inhibitor-1 (Drug)
结局指标
主要结局
The severity of psychiatric symptoms
时间窗: 6 weeks after the trial (The end of the trial)
The severity of psychiatric symptoms will be assessed by: 1. Positive and Negative Syndrome Scale(PANSS) 2. Assessment of Negative symptoms(SANS) 3. Global assessment of function(GAF)
次要结局
- Neurocognitive Function(baseline)
- Neurocognitive function(6 weeks after the trial (The end of the trial))
- The severity of psychiatric symptoms(6 weeks after the trial (the end of the trial))
研究者
Hsien-Yuan Lane
Department of Psychiatry, China Medical University Hospital
China Medical University Hospital