■肌萎缩侧索硬化症(ALS)是一种难以治愈的神经系统疾病。它是一种进行性疾病,其特征是由上运动神经元和下运动神经元的选择性易损性引起的肌肉萎缩和无力。在疾病研究中,通常使用在家族性ALS的负责基因中携带突变的小鼠模型作为ALS的病理模型。然而,没有模型可以再现人类脊髓病理的实际情况。因此,我们开发了一种使用人诱导多能干细胞(iPSCs)产生人脊髓运动神经元的方法,以及一种用于药物筛选的创新实验技术。因此,盐酸罗匹尼罗在考虑了其在大脑中的较好的传递性和耐受性后,最终被发现,包括可能的不良反应。因此,我们探索安全,在这项临床试验中,盐酸罗匹尼罗作为ALS治疗的耐受性和有效性。
■ROPALS试验是一项安全性的单中心双盲随机平行组对照试验,耐受性,以及2至16mg剂量的盐酸罗匹尼罗缓释片(RequipCR)在ALS患者中的疗效。将招募20名患者用于活性药物组(15名患者)和安慰剂组(5名患者)。如果在该试验期间不改变剂量,所有患者将能够接受利鲁唑的标准ALS治疗。主要结果是24周时的安全性和耐受性,从随机化之日起定义。次要结果将是疗效,包括ALS功能评定量表(ALSFRS-R)的任何更改,功能和生存综合评估(CAFS)的变化,和复合终点为各种临床项目的Z转换评分的总和。值得注意的是,我们将进行探索性搜索,使用患者来源的iPSCs进行药物效果评估,以证明本试验的概念.符合条件的患者将有ElEscorial可能性,临床可能和实验室支持,临床上可能的,或临床明确的肌萎缩侧索硬化症,病程小于60个月(含60个月),所有项目的ALSFRS-R评分≥2分,年龄为20~80岁.
患者招募于2018年12月开始,最后一名患者预计将于2020年11月完成试验方案。
■当前对照试验UMIN000034954和JMA-IA00397。
■1.6版(日期;2019年4月5日)。
UNASSIGNED: Amyotrophic lateral sclerosis (ALS) is an intractable and incurable neurological disease. It is a progressive disease characterized by muscle atrophy and weakness caused by selective vulnerability of upper and lower motor neurons. In disease research, it has been common to use mouse models carrying mutations in responsible genes for familial ALS as pathological models of ALS. However, there is no model that has reproduced the actual conditions of human spinal cord pathology. Thus, we developed a method of producing human spinal motor neurons using human induced pluripotent stem cells (iPSCs) and an innovative experimental technique for drug screening. As a result, ropinirole hydrochloride was eventually discovered after considering such results as its preferable transitivity in the brain and tolerability, including possible adverse reactions. Therefore, we explore the safety, tolerability and efficacy of ropinirole hydrochloride as an ALS treatment in this clinical
trial.
UNASSIGNED: The ROPALS
trial is a single-center double-blind randomized parallel group-controlled
trial of the safety, tolerability, and efficacy of the ropinirole hydrochloride extended-release tablet (Requip CR) at 2- to 16-mg doses in patients with ALS. Twenty patients will be recruited for the active drug group (fifteen patients) and placebo group (five patients). All patients will be able to receive the standard ALS treatment of riluzole if not changed the dosage during this
trial. The primary outcome will be safety and tolerability at 24 weeks, defined from the date of randomization. Secondary outcome will be the efficacy, including any change in the ALS Functional Rating Scale-Revised (ALSFRS-R), change in the Combined Assessment of Function and Survival (CAFS), and the composite endpoint as a sum of Z-transformed scores on various clinical items. Notably, we will perform an explorative search for a drug effect evaluation using the patient-derived iPSCs to prove this
trial concept. Eligible patients will have El Escorial Possible, clinically possible and laboratory-supported, clinically probable, or clinically definite amyotrophic lateral sclerosis with disease duration less than 60 months (inclusive), an ALSFRS-R score ≥2 points on all items and age from 20 to 80 years.
UNASSIGNED: Patient recruitment began in December 2018 and the last patient is expected to complete the trial protocol in November 2020.
UNASSIGNED: Current controlled trials UMIN000034954 and JMA-IIA00397.
UNASSIGNED: version 1.6 (Date; 5/Apr/2019).