Abstract：
Higher urate levels are associated with improved ALS survival in retrospective studies, however whether raising urate levels confers a survival advantage is unknown. In the Safety of Urate Elevation in Amyotrophic Lateral Sclerosis (SURE-ALS) trial, inosine raised serum urate and was safe and well-tolerated. The SURE-ALS2 trial was designed to assess longer term safety. Functional outcomes and a smartphone application were also explored.
Participants were randomized 2:1 to inosine (n = 14) or placebo (n = 9) for 20 weeks, titrated to serum urate of 7-8 mg/dL. Primary outcomes were safety and tolerability. Functional outcomes were measured with the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R). Mobility and ALSFRS-R were also assessed by a smartphone application.
During inosine treatment, mean urate ranged 5.68-6.82 mg/dL. Treatment-emergent adverse event (TEAE) incidence was similar between groups (p > .10). Renal TEAEs occurred in three (21%) and hypertension in one (7%) of participants randomized to inosine. Inosine was tolerated in 71% of participants versus placebo 67%. Two participants (14%) in the inosine group experienced TEAEs deemed related to treatment (nephrolithiasis); one was a severe adverse event. Mean ALSFRS-R decline did not differ between groups (p = .69). Change in measured home time was similar between groups. Digital and in-clinic ALSFRS-R correlated well.
Inosine met pre-specified criteria for safety and tolerability. A functional benefit was not demonstrated in this trial designed for safety and tolerability. Findings suggested potential utility for a smartphone application in ALS clinical and research settings.
Participants were randomized 2:1 to inosine (n = 14) or placebo (n = 9) for 20 weeks, titrated to serum urate of 7-8 mg/dL. Primary outcomes were safety and tolerability. Functional outcomes were measured with the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R). Mobility and ALSFRS-R were also assessed by a smartphone application.
During inosine treatment, mean urate ranged 5.68-6.82 mg/dL. Treatment-emergent adverse event (TEAE) incidence was similar between groups (p > .10). Renal TEAEs occurred in three (21%) and hypertension in one (7%) of participants randomized to inosine. Inosine was tolerated in 71% of participants versus placebo 67%. Two participants (14%) in the inosine group experienced TEAEs deemed related to treatment (nephrolithiasis); one was a severe adverse event. Mean ALSFRS-R decline did not differ between groups (p = .69). Change in measured home time was similar between groups. Digital and in-clinic ALSFRS-R correlated well.
Inosine met pre-specified criteria for safety and tolerability. A functional benefit was not demonstrated in this trial designed for safety and tolerability. Findings suggested potential utility for a smartphone application in ALS clinical and research settings.
摘要：
目的：在回顾性研究中，较高的尿酸水平与改善的ALS生存率相关，然而，提高尿酸水平是否赋予生存优势是未知的。在肌萎缩性侧索硬化症（SURE-ALS）试验中，乌兰度升高的安全性，肌苷可提高血清尿酸，安全且耐受性良好。SURE-ALS2试验旨在评估长期安全性。还探索了功能结果和智能手机应用程序。
方法：参与者被随机分为肌苷（n=14）或安慰剂（n=9），共20周，滴定至7-8mg/dL的血清尿酸。主要结果是安全性和耐受性。使用修订的肌萎缩侧索硬化功能评定量表（ALSFRS-R）测量功能结果。还通过智能手机应用程序评估了移动性和ALSFRS-R。
结果：在肌苷治疗期间，平均尿酸范围为5.68-6.82mg/dL。治疗引起的不良事件（TEAE）发生率在组间相似（P>0.10）。3例（21％）出现肾脏TEAE，1例（7％）出现高血压，随机接受肌苷治疗。71％的参与者耐受肌苷，而安慰剂为67％。肌苷组的两名参与者（14％）经历了被认为与治疗有关的TEAE（肾结石）；一个是SAE。平均ALSFRS-R下降在组间没有差异(P=0.69)。测量的家庭时间的变化在组间相似。数字和临床ALSFRS-R相关性良好。
结论：肌苷符合预先规定的安全性和耐受性标准。在设计安全性和耐受性的本试验中未证明功能益处。研究结果表明，智能手机在ALS临床和研究环境中的应用具有潜在的实用性。本文受版权保护。保留所有权利。
方法：参与者被随机分为肌苷（n=14）或安慰剂（n=9），共20周，
结果：在肌苷治疗期间，
结论：肌苷符合预先规定的安全性和耐受性标准。
