Dual Modulation of Sigma-1 and NMDA Receptors in the Treatment of Schizophrenia
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Change of Positive and Negative Syndrome Scale (PANSS)
研究概览
简要总结
sigma-1 receptor (S1R) agonistic property have been tested in clinical trials for the treatment of schizophrenia. In addition, previous studies found that some NMDA receptor (NMDAR)-enhancing agents were able to improve clinical symptoms of patients with chronic schizophrenia. Whether combined treatment of an S1R agonist and an NMDA-enhancing agent can be better than an S1R agonist alone deserves study.
详细描述
The current treatment for schizophrenia remains unsatisfactory; thus, development of new treatments is vital. Both sigma-1 receptor (S1R) dysfunction and NMDA receptor (NMDAR) hypofunction contribute to pathogenesis of schizophrenia, especially treatment-resistant schizophrenia. Several S1R agonists have been tested for its potential for schizophrenia treatment; however, its efficacy appears limited. In addition, previous studies also found that some NMDA-enhancing agents were able to augment efficacy of antipsychotics in the treatment of chronic schizophrenia. Whether combined treatment of an S1R agonist and an NMDA-enhancer (NMDAE) can be better than an S1R agonist alone deserves study. Therefore, this study aims to compare an S1R agonist plus an NMDAE and an S1R agonist plus placebo in the treatment of treatment-resistant schizophrenia. The subjects are the patients with treatment-resistant schizophrenia who have responded poorly to two or more kinds of antipsychotics treatment. They keep their original treatment and are randomly, double-blindly assigned into two treatment groups for 12 weeks: (1) S1R agonist (S1RA) plus NMDAE, or (2) S1RA plus placebo. Clinical performances and side effects are measured at weeks 0, 2, 4, 6, and 8. Cognitive functions are assessed at baseline and at endpoint of treatment by a battery of tests. The efficacies of S1RA plus NMDAE and S1RA plus placebo will be compared.
Chi-square (or Fisher's exact test) will be used to compare differences of categorical variables and t-test (or Mann-Whitney test if the distribution is not normal) for continuous variables between treatment groups. Mean changes from baseline in repeated-measure assessments will be assessed using the generalized estimating equation (GEE). All p values for clinical measures will be based on two-tailed tests with a significance level of 0.05.
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
- Triple (Participant, 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
- •Have a DSM-5 (American Psychiatric Association) diagnosis of schizophrenia
- •Are resistant to adequate treatments of at least two antipsychotics (excluding clozapine)
- •Remain symptomatic but without clinically significant fluctuation, while their antipsychotic doses are unchanged for at least 3 months and will be maintained during the period of the 8-week trial
- •PANSS total score >70
- •Hamilton Depression Rating Scale-17 items (HAMD) <7
- •Are physically healthy and laboratory assessments (including blood routine, biochemical tests) are clinically insignificant.
- •Have sufficient education to communicate effectively and are capable of completing the assessments of the study.
- •Agree to participate in the study and provide informed consent
排除标准
- •DSM-5 diagnosis of intellectual disability or substance (including alcohol) use disorder
- •History of epilepsy, head trauma, central nervous system diseases or mental disorders other than schizophrenia (including major depressive disorder, bipolar disorders, persistent depressive disorder, obsessive-compulsive disorder)
- •Pregnancy or lactation
- •Inability to follow protocol
研究组 & 干预措施
S1R agonist (S1RA) plus NMDAE
An S1R agonist plus an NMDA enhancer
干预措施: S1RA plus NMDAE (Drug)
S1R agonist (S1RA) plus placebo
An S1R agonist plus placebo
干预措施: S1RA plus Placebo Cap (Drug)
结局指标
主要结局
Change of Positive and Negative Syndrome Scale (PANSS)
时间窗: week 0, 2, 4, 6, 8
Assessment of overall symptoms. Minimum value: 30, maximum value:210, the higher scores mean a worse outcome.
次要结局
- Change of scales for the Assessment of Negative Symptoms (SANS) total score(week 0, 2, 4, 6, 8)
- Positive subscale, Negative subscales, and General Psychopathology subscale of PANSS(week 0, 2, 4, 6, 8)
- Clinical Global Impression(week 0, 2, 4, 6, 8)
- Global Assessment of Functioning(week 0, 2, 4, 6, 8)
- Quality of Life Scale(week 0, 2, 4, 6, 8)
- Cognitive function(Week 0, 8)