帕金森病患者应用N-乙酰半胱氨酸的随机、安慰剂对照试验：一项初步研究。
完整摘要 · 中文译文
这项先导试验评估了口服N-乙酰半胱氨酸（NAC）1200 mg/天在帕金森病（PD）患者中的一年耐受性，并探索其与临床进展、左旋多巴剂量和纹状体多巴胺转运蛋白显像的相关性。42名患者在常规治疗基础上被随机分配至NAC或匹配安慰剂组，每日两次，持续12个月。完成者（n = 32）在基线和12个月时接受评估，包括原始UPDRS第I-IV部分、99mTc-TRODAT-1 SPECT、处方左旋多巴剂量以及肝/肾功能检查。分析包括配对t检验、变化分数的Welch检验，以及含组别×时间交互作用并经年龄、性别和病程校正的线性混合效应模型。未进行多重性校正；结果为探索性。42名随机患者中有32名完成了两次访视。两组UPDRS总分均升高，但NAC组的升高小于安慰剂组（平均Δ +5.4 vs. +9.5分；差异 -4.1，95% CI -7.6至-0.5；p = 0.028；混合模型组别×时间 p = 0.024）。情绪项变化也存在差异（差异 -0.64，95% CI -1.17至-0.11；p = 0.020）。NAC组的TRODAT结合下降较少（变化差异 +5.5单位，95% CI 1.7至9.3；p = 0.006；组别×时间 p = 0.004）。≤4年病程亚组包括NAC组9/17（53%）和安慰剂组7/15（47%）的参与者，并显示出相似模式。经ANCOVA对基线剂量、年龄、性别和病程校正后，两组间左旋多巴剂量变化无显著性（校正后差异 -86 mg/天，95% CI -235至+64；p = 0.25）。完成者的实验室检查值稳定；停药情况不常见。 对不良事件进行了特征描述。与安慰剂相比，为期一年的口服NAC与更有利的探索性临床和影像学轨迹相关。完成者的实验室检查结果无异常，但仅凭完成者无法确立安全性。这些数据并未证实疾病修饰作用，需在更大规模、预先设定检验效力的试验中加以确认。
完整摘要 · 英文原文
This pilot trial evaluated the one-year tolerability of oral N-acetylcysteine (NAC) 1200 mg/day in Parkinson's disease (PD) and explored associations with clinical progression, levodopa dose, and striatal dopamine-transporter imaging. Forty-two patients were randomized to NAC or matching placebo twice daily for 12 months in addition to usual care. Completers (n = 32) were assessed at baseline and 12 months with the original UPDRS parts I-IV, 99mTc-TRODAT-1 SPECT, prescribed levodopa dose, and liver/kidney tests. Analyses included paired t-tests, Welch tests of change scores, and linear mixed-effects models with a group × time interaction adjusted for age, sex, and disease duration. No multiplicity correction was applied; results are exploratory. Thirty-two of 42 randomized patients completed both visits. Total UPDRS increased in both groups, but less with NAC than placebo (mean Δ + 5.4 vs. + 9.5 points; difference - 4.1, 95% CI - 7.6 to - 0.5; p = 0.028; mixed-model group × time p = 0.024). Mood-item change also differed (difference - 0.64, 95% CI - 1.17 to - 0.11; p = 0.020). TRODAT binding declined less with NAC (difference in change + 5.5 units, 95% CI 1.7 to 9.3; p = 0.006; group × time p = 0.004). The ≤ 4-year subgroup comprised 9/17 (53%) NAC and 7/15 (47%) placebo participants and showed a similar pattern. Levodopa-dose change was not significant between groups after ANCOVA adjustment for baseline dose, age, sex, and disease duration (adjusted difference - 86 mg/day, 95% CI - 235 to + 64; p = 0.25). Completer laboratory values were stable; discontinuations were not characterized for adverse events. One-year oral NAC was associated with more favorable exploratory clinical and imaging trajectories than placebo. Completer laboratories were unremarkable, but safety cannot be established from completers alone. These data do not establish disease modification and require confirmation in a larger, prospectively powered trial.