Abstract

Objective: 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. Design: 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. Setting: Exercise physiology laboratory in a single clinical research center. Participants: Ambulatory subjects (N=48; age range, 9–17y) with genetically confirmed FA. Intervention: Idebenone administered orally 3 times a day for a total daily dose of approximately 5, 15, and 45mg/kg or matching placebo for 6 months. Main Outcome Measures: Peak oxygen consumption per unit time (peak VO2) 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. Results: Baseline mean peak VO2 ± SD was 746 ± 246mL/min (16.2 ± 5.8 mL/kg/min), and WR was 40 ± 23 W for all subjects. Peak VO2 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 VO2 or WR after idebenone treatment at any dose level relative to placebo. Conclusions: 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. Verf.-Referat