TY - JOUR
T1 - Exercise Capacity and Idebenone Intervention in Children and Adolescents With Friedreich Ataxia
AU - Drinkard, Bart E.
AU - Keyser, Randall E.
AU - Paul, Scott M.
AU - Arena, Ross
AU - Plehn, Jonathan F.
AU - Yanovski, Jack A.
AU - Di Prospero, Nicholas A.
N1 - Funding Information:
The present investigation was an exploratory, secondary endpoint in a phase II clinical trial conducted at the National Institutes of Health (Mark O. Hatfield Clinical Research Center, Bethesda, MD; Clinicaltrials.gov registry NCT00229632 ). 19 Forty-eight subjects with genetically confirmed FA were enrolled in a 6-month, randomized, double-blind, placebo-controlled study of the effects of idebenone treatment on an oxidative stress biomarker. Eligible participants were age 9 to 17 years, weighed 30 to 80kg, were neurologically symptomatic, and were able to walk 7.5 meters with or without an assistive device. No subject was exposed to idebenone or other antioxidants or dietary supplements for at least 1 month prior to enrollment. Exclusion criteria included hypersensitivity to idebenone, serious concomitant illness, and safety laboratory values outside the normal reference ranges (hematology, biochemistry, coagulation, urinalysis) as previously described. 19 All subjects underwent medical screening and physical examination prior to enrollment. At screening, informed assent was obtained from all subjects and informed consent from their parents or legal guardians. This study was approved and conducted in accordance with policies and procedures set forth by the National Institute of Neurological Disorders and Stroke Institutional Review Board in compliance with the Declaration of Helsinki.
PY - 2010/7
Y1 - 2010/7
N2 - 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.
AB - 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.
KW - Exercise
KW - Friedreich Ataxia
KW - Idebenone [substance name]
KW - Rehabilitation
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U2 - 10.1016/j.apmr.2010.04.007
DO - 10.1016/j.apmr.2010.04.007
M3 - Article
C2 - 20599042
AN - SCOPUS:77953832142
SN - 0003-9993
VL - 91
SP - 1044
EP - 1050
JO - Archives of physical medicine and rehabilitation
JF - Archives of physical medicine and rehabilitation
IS - 7
ER -