Rehabilitation Medicine Department, Hatfield Clinical Research Center, National Institutes of Health, Bethesda, MD 20892-1604, USA.
Arch Phys Med Rehabil. 2010 Jul;91(7):1044-50. doi: 10.1016/j.apmr.2010.04.007.
To determine the exercise capacity of children and adolescents with Friedreich's Ataxia (FA) and to evaluate the effects of 6 months of idebenone treatment on exercise capacity.
Exploratory endpoint in a randomized double-blind, placebo-controlled, phase II clinical trial designed to investigate the effects of idebenone on a biomarker of oxidative stress.
Exercise physiology laboratory in a single clinical research center.
Ambulatory subjects (N=48; age range, 9-17 y) with genetically confirmed FA.
Idebenone administered orally 3 times a day for a total daily dose of approximately 5, 15, and 45 mg/kg or matching placebo for 6 months.
Peak oxygen consumption per unit time (peak VO(2)) and peak work rate (WR) were measured during incremental exercise testing at baseline and after treatment. Echocardiography and neurologic assessments were also completed before and after treatment.
Baseline mean peak VO(2) +/- SD was 746+/-246 mL/min (16.2+/-5.8 mL/kg/min), and WR was 40+/-23 W for all subjects. Peak VO(2) and WR were correlated with short guanine-adenine-adenine allele length and neurologic function. Relative left ventricular wall thickness was increased but left ventricular ejection fraction was normal in most subjects; there was no relationship between any exercise and echocardiographic measures. There were no significant changes in mean peak VO(2) or WR after idebenone treatment at any dose level relative to placebo.
Exercise capacity in children and adolescents with FA was significantly impaired. The basis for the impairment appears to be multifactorial and correlated to the degree of neurologic impairment. Although idebenone has previously been shown potentially to improve features of FA, idebenone treatment did not increase exercise capacity relative to placebo.
确定弗里德里希共济失调（FA）患儿和青少年的运动能力，并评估 6 个月艾地苯醌治疗对运动能力的影响。
在一项旨在研究艾地苯醌对氧化应激生物标志物影响的随机双盲、安慰剂对照、二期临床试验中，探索终点。
单一临床研究中心的运动生理学实验室。
48 名（年龄范围，9-17 岁）经基因证实的 FA 患儿，能进行日常活动。
艾地苯醌每天口服 3 次，总日剂量约为 5、15 和 45mg/kg，或匹配的安慰剂，共 6 个月。
在基线和治疗后进行递增运动试验时，测量单位时间的峰值耗氧量（峰值 VO₂）和峰值工作率（WR）。在治疗前后还完成了超声心动图和神经评估。
所有受试者的基线平均峰值 VO₂±SD 为 746±246mL/min（16.2±5.8mL/kg/min），WR 为 40±23W。峰值 VO₂和 WR 与短鸟嘌呤-腺嘌呤-腺嘌呤等位基因长度和神经功能相关。大多数受试者的左心室壁相对厚度增加，但左心室射血分数正常；运动与超声心动图测量之间没有关系。与安慰剂相比，任何剂量水平的艾地苯醌治疗后，平均峰值 VO₂或 WR 均无显著变化。
FA 患儿和青少年的运动能力明显受损。这种损伤的基础似乎是多因素的，并与神经损伤的程度相关。尽管艾地苯醌以前曾显示出可能改善 FA 的特征，但与安慰剂相比，艾地苯醌治疗并未增加运动能力。
