Department of Neurology, Philipps University Marburg, Marburg, Germany.
Institute for Neurogenomics, Helmholtz Center for Environment and Health, Munich, Germany.
NEJM Evid. 2023 Sep;2(9):EVIDoa2200311. doi: 10.1056/EVIDoa2200311. Epub 2023 Aug 22.
Epidemiologic studies show that smokers have a lower incidence of Parkinson’s disease. Nicotine has been hypothesized to slow progression in early Parkinson’s disease. METHODS: In a double-blind, placebo-controlled multicenter trial, we randomly assigned patients with Parkinson’s disease, diagnosed within 18 months, who were in Hoehn and Yahr disease stage less than or equal to 2 (range from 0 to 5; higher scores indicate greater impairment), who were therapy naïve (except for stable monoamine-oxidase-B inhibition), and not requiring dopaminergic therapy, to transdermal nicotine or placebo. The primary end point was change in Unified Parkinson’s Disease Rating Scale parts I–III (Total UPDRS) score (range from 0 to 172; higher scores indicate greater impairment) between baseline and 60 weeks (52 weeks of trial therapy, 8 weeks of washout). The first secondary end point was change in Total UPDRS from baseline to 52 weeks. Differences between groups were estimated using the Hodges–Lehmann (HL) method and tested with the exact two-sided stratified Mann–Whitney–Wilcoxon test according to the intention-to-treat principle. RESULTS: Among 163 participants, 101 were assessed for the primary end point. Mean worsening of Total UPDRS was 3.5 in the placebo versus 6.0 in the nicotine group (HL-difference with 95% CI: –3 [–6 to 0], P=0.06). For the first secondary end point, analysis of 138 participants showed a mean worsening of 5.4 in the placebo versus 9.1 in the nicotine group (HL-difference with 95% CI: –4 [–7 to –1]). Dropout was mainly because of early treatment discontinuation or adverse events. Cutaneous adverse effects at the patch application site were common. In all, 34.6% of participants initiated dopaminergic therapy during participation. CONCLUSIONS: One-year transdermal nicotine treatment did not slow progression in early Parkinson’s disease. (Funded by the Michael J. Fox Foundation for Parkinson’s Research and others; ClinicalTrials.gov number, NCT01560754; EudraCT number, 2010-020299-42.)
流行病学研究表明，吸烟者帕金森病的发病率较低。尼古丁被假设可以减缓早期帕金森病的进展。
在一项双盲、安慰剂对照的多中心试验中，我们随机分配了在 Hoehn 和 Yahr 疾病阶段 1 至 2 级（范围为 0 至 5；分数越高表示损伤越严重）的帕金森病患者，这些患者在诊断后 18 个月内接受了治疗，他们没有接受过多巴胺能治疗，也不需要多巴胺能治疗，接受透皮尼古丁或安慰剂治疗。主要终点是统一帕金森病评定量表（UPDRS）I-III 部分（总分 UPDRS）评分从基线到 60 周（52 周试验治疗，8 周洗脱期）的变化（范围为 0 至 172；分数越高表示损伤越严重）。第一个次要终点是从基线到 52 周时总分 UPDRS 的变化。使用 Hodges–Lehmann（HL）方法估计组间差异，并根据意向治疗原则，使用精确的双侧分层 Mann–Whitney–Wilcoxon 检验进行检验。
在 163 名参与者中，有 101 名评估了主要终点。安慰剂组的总 UPDRS 恶化平均值为 3.5，尼古丁组为 6.0（HL 差值 95%CI：-3 [6 至 0]，P=0.06）。对于第一个次要终点，对 138 名参与者的分析显示，安慰剂组的总 UPDRS 恶化平均值为 5.4，尼古丁组为 9.1（HL 差值 95%CI：-4 [7 至-1]）。脱落主要是因为早期治疗中断或不良事件。贴片应用部位的皮肤不良反应很常见。共有 34.6%的参与者在参与期间开始接受多巴胺能治疗。
为期一年的透皮尼古丁治疗并不能减缓早期帕金森病的进展。（由迈克尔·J·福克斯帕金森病研究基金会等资助；ClinicalTrials.gov 编号，NCT01560754；EudraCT 编号，2010-020299-42。）
