Data_Sheet_1_Slower progression of amyotrophic lateral sclerosis with external application of a Chinese herbal plaster–The randomized, placebo-controlled triple-blinded ALS-CHEPLA trial.docx

BackgroundAmyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disease characterized by gradually increasing damage to the upper and lower motor neurons. However, definitive and efficacious treatment for ALS is not available, and oral intake in ALS patients with bulbar involvement is complicated due to swallowing difficulties.
Hypothesis/purposeThis study investigated whether the external plaster application of the herbal composition Ji-Wu-Li efficiently slows ALS progression because prior studies obtained promising evidence with oral herbal applications.
Study designThe randomized, triple-blinded study compared the efficacy, safety, and tolerability of the application of Ji-Wu-Li plaster (JWLP) with placebo plaster (PLAP).
MethodsIn total, 120 patients with definite ALS, clinically probable ALS, or clinically probable laboratory-supported ALS were randomized in a 1:1 ratio to receive JWLP or PLAP. Patients were treated and observed for 20 weeks. The primary outcome was the ALSFRS-R score, while the secondary outcomes were the ALS-SSIT score and weight loss.
ResultsThe mean±SD decrease in the ALSFRS-R over 20 weeks differed by 0.84 points in a group comparison (JWLP, −4.44 ± 1.15; PLAP, −5.28 ± 1.98; p = 0.005). The mean increase in the ALS-SSIT over 20 weeks differed by 2.7 points in a group comparison (JWLP, 5.361.15; PLAP, 8.06 ± 1.72; p < 0.001). The mean weight loss over 20 weeks differed by 1.65 kg in a group comparison (JWLP, −3.98 ± 2.61; PLAP, −5.63 ± 3.17; p = 0.002). Local allergic dermatitis suspected as causal to the intervention occurred in 10 of 60 participants in the JWLP group and 9 of 60 participants in the PLAP group. Systemic adverse events were mild, temporary, and considered unrelated to the intervention.
ConclusionThe JWLP showed clinical efficacy in the progression of ALS, as measured by the ALSFRS-R, ALS-SSIT, and weight loss in a randomized, placebo-controlled trial. Because skin reactions occurred in both groups, the covering material needs improvement. All of the Ji Wu Li herbal ingredients regulate multiple mechanisms of neurodegeneration in ALS. Hence, JWLP may offer a promising and safe add-on therapy for ALS, particularly in patients with bulbar involvement, but a confirmative long-term multicentre study is required.

背景：肌萎缩侧索硬化症（Amyotrophic lateral sclerosis, ALS）是一类慢性神经退行性疾病，以上下运动神经元进行性损伤为核心特征。目前临床尚无确切有效的治疗方案，伴球部受累的ALS患者因存在吞咽困难，经口进食面临复杂障碍。
假设/研究目的：本研究旨在探讨外用中药复方芪五利（Ji-Wu-Li）贴剂能否有效延缓ALS进展，既往已有研究证实口服中药制剂对此类疾病具有潜在应用价值。
研究设计：本研究为随机三盲临床试验，对比芪五利贴剂（Ji-Wu-Li plaster, JWLP）与安慰剂贴剂（placebo plaster, PLAP）的疗效、安全性及耐受性。
研究方法：共纳入120例确诊ALS、临床拟诊ALS或临床拟诊实验室支持型ALS患者，以1:1比例随机分配至JWLP组或PLAP组，接受为期20周的治疗与随访。本研究的主要结局指标为ALSFRS-R评分，次要结局指标为ALS-SSIT评分与体重变化量。
研究结果：20周随访期间，两组ALSFRS-R评分的平均±标准差降幅相差0.84分（JWLP组：-4.44±1.15；PLAP组：-5.28±1.98；p=0.005）。ALS-SSIT评分的平均增幅组间相差2.7分（JWLP组：5.36±1.15；PLAP组：8.06±1.72；p<0.001）。20周内的平均体重降幅组间相差1.65kg（JWLP组：-3.98±2.61；PLAP组：-5.63±3.17；p=0.002）。JWLP组60例受试者中，10例出现疑似与干预措施相关的局部过敏性皮炎；PLAP组60例受试者中则有9例出现此类反应。全身性不良事件均为轻度、一过性，且被判定与干预无关。
研究结论：本随机安慰剂对照临床试验结果显示，通过ALSFRS-R、ALS-SSIT评分及体重变化评估，JWLP可显著延缓ALS的疾病进展。由于两组均出现皮肤不良反应，贴剂的覆盖材料仍需进一步优化。所有芪五利中药活性成分均可调控ALS神经退行性变的多条通路。因此，JWLP或可为ALS患者（尤其是伴球部受累者）提供一种兼具前景与安全性的附加治疗方案，但仍需开展长期多中心的确证性研究以验证其疗效。