Exercise Capacity and Idebenone Intervention in Children and Adolescents With Friedreich Ataxia

• Published in: Archives of physical medicine and rehabilitation Vol. 91; no. 7; pp. 1044 - 1050
• Main Authors: Drinkard, Bart E., MSPT, Keyser, Randall E., PhD, Paul, Scott M., MD, Arena, Ross, PhD, PT, Plehn, Jonathan F., MD, Yanovski, Jack A., MD, PhD, Di Prospero, Nicholas A., MD, PhD
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.07.2010; Elsevier
• Subjects: Adolescence; Adolescent; Antioxidants - administration & dosage; Antioxidants - therapeutic use; Biological and medical sciences; Child; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - urine; Diseases of the osteoarticular system; Dose-Response Relationship, Drug; Double-Blind Method; Exercise; Exercise Test; Female; Friedreich Ataxia; Friedreich Ataxia - drug therapy; Friedreich Ataxia - metabolism; Friedreich Ataxia - physiopathology; Humans; Idebenone [substance name]; Male; Medical sciences; Miscellaneous; Neurology; Oxidative Stress - drug effects; Oxygen Consumption - drug effects; Physical Medicine and Rehabilitation; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Rehabilitation; Ubiquinone - administration & dosage; Ubiquinone - analogs & derivatives; Ubiquinone - therapeutic use; work rate; LV; ICARS; International Cooperative Ataxia Rating Scale; Exercise; deoxyribonucleic acid; Friedreich Ataxia Rating Scale; respiratory exchange ratio; left ventricular; WR; FARS; guanine-adenine-adenine; SV; GAA; peak VO 2; peak oxygen consumption per unit time; RWT; stroke volume; Idebenone [substance name]; DNA; adenosine triphosphate; Rehabilitation; FA; relative wall thickness; Friedreich Ataxia; ATP; RER; Human; Physical exercise; Nervous system diseases; Psychotropic; Benzoquinone derivatives; Idebenone; Genetic disease; Cerebral disorder; Reeducation; Nootropic agent; Orthopedics; Central nervous system disease; Adolescent; Degenerative disease; Friedreich ataxia; Spinal cord disease; Child
• ISSN: 0003-9993; 1532-821X
• DOI: 10.1016/j.apmr.2010.04.007

Abstract Drinkard BE, Keyser RE, Paul SM, Arena R, Plehn JF, Yanovski JA, Di Prospero NA. Exercise capacity and idebenone intervention in children and adolescents with Friedreich ataxia. 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±5.8mL/kg/min), and WR was 40±23W 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.