A Randomized Clinical Trial of High-Dosage Coenzyme Q10 in Early Parkinson Disease No Evidence of Benefit
A Randomized Clinical Trial of High-Dosage Coenzyme Q10 in Early Parkinson Disease No Evidence of Benefit
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DOI：
10.1001/jamaneurol.2014.131
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发表时间：
2014-05-01
期刊：
影响因子：
29
通讯作者：
Boyar, Karyn
中科院分区：
文献类型：
--
作者：
Beal, M. Flint;Oakes, David;Boyar, Karyn
辅酶Q10（CoQ 10）是一种支持线粒体功能的抗氧化剂，已在临床前帕金森病（PD）模型中显示可减少多巴胺神经元的损失，并且在早期人体研究中安全且耐受性良好。先前的II期研究建议可能的clinical benefit.Objective要检查辅酶Q10是否可以减缓疾病进展在早期PD.DESIGN，设置，和参与者一个III期随机，安慰剂对照，双盲临床试验在67个北美网站组成的参与者30岁或以上谁收到的PD诊断在5年内，谁有以下纳入标准：存在静止性震颤、运动迟缓和僵硬;改良Hoehn和Yahr分期为2.5或更低;并且预期在3个月内不需要多巴胺能治疗。排除标准包括在60天内使用任何PD药物，使用任何症状性PD药物超过90天，非典型或药物诱导的帕金森综合征，任何肢体的统一帕金森病评定量表（Unified Parkinson's Disease Rating Scale，简称EADS）静息震颤评分为3或更高，简易精神状态检查评分为25或更低，中风史，使用某些补充剂，以及最近大量接触辅酶Q10 696名参与者筛选，78人被发现是不合格的，18人拒绝participation.INTERVENTIONS其余600名参与者被随机分配到接受安慰剂，1200毫克/天的辅酶Q10，或2400毫克/天的辅酶Q10;所有参与者均接受1200 IU/d的维生素E。主要结果和措施参与者观察16个月或直到残疾需要多巴胺能治疗。前瞻性定义的主要结局指标是从基线到最终访视的UPDRS总分（第I-III部分）的变化。该研究的动力，以检测一个积极的治疗和安慰剂之间的3点差异。结果的基线特征的参与者是平衡的，平均年龄为62.5岁，66%的参与者是男性，平均基线总的CRISPR评分为22.7。共有267名参与者需要治疗（94名接受安慰剂，87名接受1200 mg/d辅酶Q10，86名接受2400 mg/d辅酶Q10），65名参与者（29名接受安慰剂，19名接受1200 mg/d辅酶Q10，17名接受2400 mg/d辅酶Q10）提前退出。治疗耐受性良好，无安全性问题。达到预先规定的无效标准后，终止研究。在研究终止时，两个活性治疗组均显示出相对于安慰剂的轻微不良趋势。调整后的平均变化从基线至最终访视的总OSAS评分（恶化）分别为6.9分（安慰剂组）、7.5分（安慰剂组）、7.5分（安慰剂组）和7.5分（安慰剂组）。（1200 mg/d辅酶Q10;相对于安慰剂P = 0.49），8.0分辅酶Q10 2400 mg/d;相对于安慰剂，P = 0.21）。结论和相关性辅酶Q10在该人群中安全且耐受性良好，但没有表现出临床益处的证据。
IMPORTANCE Coenzyme Q10 (CoQ10), an antioxidant that supports mitochondrial function, has been shown in preclinical Parkinson disease (PD) models to reduce the loss of dopamine neurons, and was safe and well tolerated in early-phase human studies. A previous phase II study suggested possible clinical benefit.OBJECTIVE To examine whether CoQ10 could slow disease progression in early PD.DESIGN, SETTING, AND PARTICIPANTS A phase III randomized, placebo-controlled, double-blind clinical trial at 67 North American sites consisting of participants 30 years of age or older who received a diagnosis of PD within 5 years and who had the following inclusion criteria: the presence of a rest tremor, bradykinesia, and rigidity; a modified Hoehn and Yahr stage of 2.5 or less; and no anticipated need for dopaminergic therapy within 3 months. Exclusion criteria included the use of any PD medication within 60 days, the use of any symptomatic PD medication for more than 90 days, atypical or drug-induced parkinsonism, a Unified Parkinson's Disease Rating Scale (UPDRS) rest tremor score of 3 or greater for any limb, a Mini-Mental State Examination score of 25 or less, a history of stroke, the use of certain supplements, and substantial recent exposure to CoQ10. Of 696 participants screened, 78 were found to be ineligible, and 18 declined participation.INTERVENTIONS The remaining 600 participants were randomly assigned to receive placebo, 1200 mg/d of CoQ10, or 2400 mg/d of CoQ10; all participants received 1200 IU/d of vitamin E.MAIN OUTCOMES AND MEASURES Participants were observed for 16 months or until a disability requiring dopaminergic treatment. The prospectively defined primary outcome measure was the change in total UPDRS score (Parts I-III) from baseline to final visit. The study was powered to detect a 3-point difference between an active treatment and placebo.RESULTS The baseline characteristics of the participants were well balanced, the mean age was 62.5 years, 66% of participants were male, and the mean baseline total UPDRS score was 22.7. A total of 267 participants required treatment (94 received placebo, 87 received 1200 mg/d of CoQ10, and 86 received 2400 mg/d of CoQ10), and 65 participants (29 who received placebo, 19 who received 1200 mg/d of CoQ10, and 17 who received 2400 mg/d of CoQ10) withdrew prematurely. Treatments were well tolerated with no safety concerns. The study was terminated after a prespecified futility criterion was reached. At study termination, both active treatment groups showed slight adverse trends relative to placebo. Adjusted mean changes (worsening) in total UPDRS scores from baseline to final visit were 6.9 points (placebo), 7.5 points (1200 mg/d of CoQ10; P =.49 relative to placebo), and 8.0 points (2400 mg/d of CoQ10; P =.21 relative to placebo).CONCLUSIONS AND RELEVANCE Coenzyme Q10 was safe and well tolerated in this population, but showed no evidence of clinical benefit.