Background Studies suggest that dihydropyridine calcium-channel blockers may be associated with reduced risk for Parkinson disease (PD). Objective To assess the effect of isradipine, a dihydropyridine calcium-channel blocker, on the rate of clinical progression of PD. Design Multicenter, randomized, parallel-group, double-blind, placebo-controlled trial. (ClinicalTrials.gov: NCT02168842). Setting 57 Parkinson Study Group sites in North America. Participants Patients with early-stage PD (duration <3 years) who were not taking dopaminergic medications at enrollment. Intervention 5 mg of immediate-release isradipine twice daily or placebo for 36 months. Measurements The primary outcome was change in the Unified Parkinson's Disease Rating Scale (UPDRS) parts I to III score measured in the antiparkinson medication "ON" state between baseline and 36 months. Secondary outcomes included time to initiation and use of antiparkinson medications, time to onset of motor complications, change in nonmotor disability, and quality-of-life measures. Results 336 patients were randomly assigned (mean age, 62 years [SD, 9]; 68% men; disease duration, 0.9 year [SD, 0.7]; mean UPDRS part I to III score, 23.1 [SD, 8.6]); 95% of patients completed the study. Adjusted least-squares mean changes in total UPDRS score in the antiparkinson medication ON state over 36 months for isradipine and placebo recipients were 2.99 (95% CI, 0.95 to 5.03) points versus 3.26 (CI, 1.25 to 5.26) points, respectively, with a treatment effect of -0.27 (CI, -3.02 to 2.48) point (P = 0.85). Statistical adjustment for antiparkinson medication use did not change the findings. Secondary outcomes showed no effect of isradipine treatment. The most common adverse effects of isradipine were edema and dizziness. Limitation The isradipine dose may have been insufficient to engage the target calcium channels associated with neuroprotective effects. Conclusion Long-term treatment with immediate-release isradipine did not slow the clinical progression of early-stage PD. Primary Funding Source National Institute of Neurological Disorders and Stroke.

中文翻译：

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早期帕金森病中伊斯拉地平与安慰剂的比较：一项随机试验。

背景研究表明，二氢吡啶类钙通道阻滞剂可能与帕金森病（PD）的风险降低有关。目的评估二氢吡啶钙通道阻滞剂伊拉地平对PD临床进展率的影响。设计多中心，随机，平行分组，双盲，安慰剂对照试验。（ClinicalTrials.gov：NCT02168842）。在北美设置57个Parkinson Study Group网站。参与者入选时未服用多巴胺能药物的早期PD（持续时间<3年）患者。每天两次或每次使用安慰剂干预5毫克伊拉地平36个月。测量主要结果是使用帕金森抗癌药物“ ON”测得的统一帕金森氏病评分量表（UPDRS）I至III部分得分。状态在基线到36个月之间。次要结果包括开始和使用抗帕金森药物的时间，开始运动并发症的时间，非运动残疾的改变以及生活质量的衡量标准。结果336名患者被随机分配（平均年龄62岁[SD，9]；男性68％；疾病持续时间，0.9年[SD，0.7]； UPDRS第I至III部分平均评分，23.1 [SD，8.6]）；95％的患者完成了研究。异丁烷和安慰剂接受者在36个月的抗帕金森药物开启状态下，校正后的最小二乘平均UPDRS总得分变化分别为2.99（95％CI，0.95至5.03）点和3.26（CI，1.25至5.26）点。 -0.27（CI，-3.02至2.48）点的治疗效果（P = 0.85）。对抗帕金森药物使用情况的统计调整并未改变结果。次要结果显示，伊沙地平治疗无效。伊拉地平最常见的不良反应是浮肿和头晕。局限性依地平的剂量可能不足以使与神经保护作用相关的目标钙通道参与。结论长期使用速释伊拉地平治疗不能减慢早期PD的临床进展。国家神经病学和中风研究所的主要资金来源。