Gut Microbiota Alteration and Improvement of Ataxia in Patients of Multiple System Atrophy Treating With Tllsh2910 - a Randomized, Placebo-controlled, Double-blinded, Cross-over, Single-center Clinical Trial
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- =Scale for the assessment and rating of ataxia (SARA) score
研究概览
简要总结
Multiple system atrophy (MSA) is a fetal, rare neurodegenerative disease presenting with parksinonism, autonomic dysfunction, and cerebellar ataxia. Numerous anti-parkinsonism agents have been developed. However, no medication has yet been proven effective for the symptomatic or even causative treatment in cerebellar ataxia. To our knowledge, cerebellar N-methyl-D- aspartic acid (NMDA) receptors play a special role in the modulation of motor learning and coordination. Tllsh2910, a NMDA modulator, has been found to attenuate the ataxic gait in the mouse model. Here, we designed a large-scale double-blind randomized controlled, cross-over phase III trial to investigate the efficacy of Tllsh2910 in neurodegenerative ataxic patients and the association of gut microbiota change.
详细描述
The study is terminated prematurely due to project replanning and difficulty in recruitment during the pandemic. The overall sample size is not adequate to meet the requirement of estimated power. The statistical results will be investigated. No severe drug-related adverse events were reported during the study period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinically confirmed cerebellar ataxia with a SARA total score ≥ 3 (range 0-40).
- •Clinical diagnosis of probable or possible MSA-C.
- •Patients older than 18 years old and younger than 80 years old.
排除标准
- •Major systemic diseases such as hepatic, renal or heart failure, malignancy, stroke.
- •Concomitant medication which inhibit CYP2C19 enzyme such as Clopidogrel, cimetidine, fluconazole, ketoconazole, voriconazole, etravirine, fluoxetine, fluvoxamine, ticlopidine.
- •Pregnancy and/or breastfeeding.
- •Acute diseases that might interfere with the trial.
研究组 & 干预措施
Tllsh2910 to placebo
Tllsh2910 160mg per day for 12 weeks with wash-out period 12 weeks and subsequent placebos for 12 weeks.
干预措施: Tllsh2910 (Drug)
Tllsh2910 to placebo
Tllsh2910 160mg per day for 12 weeks with wash-out period 12 weeks and subsequent placebos for 12 weeks.
干预措施: Placebo (Drug)
Placebo to Tllsh2910
Placebos for 12 weeks with wash-out period 12 weeks and subsequent Tllsh2910 160mg per day for 12 weeks
干预措施: Tllsh2910 (Drug)
Placebo to Tllsh2910
Placebos for 12 weeks with wash-out period 12 weeks and subsequent Tllsh2910 160mg per day for 12 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
=Scale for the assessment and rating of ataxia (SARA) score
时间窗: Baseline, 12 weeks, 24 weeks, 36 weeks
SARA is an 8-item performance based scale with gait, stance, sitting, speech disturbance, finger chase, nose-finger test, fast alternative hand movements, and heel-shin slide, yielding a total score of 0 (no ataxia) to 40 (most severe ataxia). The change in the SARA score will be recorded from period-level baseline to the end of the 12-week, 24-week, 36-week treatment period.
次要结局
- The change of total time needed for a 8-meter walking test(Baseline, 12 weeks, 24 weeks, 36 weeks)
- The total time needed for 9 hole peg test(Baseline, 12 weeks, 24 weeks, 36 weeks)
- International Cooperative Ataxia Rating Scale (ICARS) score(Baseline, 12 weeks, 24 weeks, 36 weeks)
- Unified multiple system atrophy rating scale (UMSARS) Part II score(Baseline, 12 weeks, 24 weeks, 36 weeks)
- The composition change of gut microbiota(Baseline, 12 weeks)
- The change of the World Health Organization Quality of Life (WHOQOL-BREF) scale(Baseline, 12 weeks, 24 weeks, 36 weeks)