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

Abstract

Objective To determine the effects of idebenone on exercise capacity in children and adolescents with Friedreich’s Ataxia. Design Secondary analysis of a randomized double-blind, placebo controlled, phase II clinical trial. Setting Clinical research center, exercise physiology laboratory. Participants 42 subjects (ages 9–17) with genetically confirmed FA. Intervention Six-month idebenone regimens of approximately 5, 15, and 45 mg/kg/day or placebo. Main Outcome Variables Peak oxygen consumption (peak VO2) and peak work rate (WR) were measured during incremental exercise tests before and after treatment. Echocardiography and neurological assessments were also completed before and after theidebenone regimen. Results Baseline peak VO2 was 746+246 ml/min (16.2 ± 5.8 ml/kg/min) and WR was 40+23 watts in all subjects combined. Peak VO2 and WR were correlated with short GAA repeat length and neurological assessments. Relative left ventricular wall thickness (RWT) was increased but left ventricular ejection fraction was normal in the majority of subjects; there was no relationship between any exercise and echocardiographic measure. There were no significant changes in peak VO2 or WR after idebenone treatment. Conclusions Exercise capacity was severely impaired in these children and adolescents with FA and after 6 months of idebenone treatment did not change by an amount thought to be clinically relevant.

Hypertrophic cardiomyopathy in children

“…Treatment with the antioxidant idebenone may reduce the degree of LV hypertrophy,28 although the clinical significance of this has not yet been evaluated 29. In a placebo-controlled trial in children with FA, treatment with idebenone did not improve exercise capacity 30. Other neuromuscular disorders associated with HCM include myotonic dystrophy, Refsum disease and mutations in lamin-associated protein genes.…”

Improvements in Quality of Life in Individuals with Friedreich’s Ataxia after Participation in a 5-Year Program of Physical Activity: An observational Study Pre-Post Test Design, and Two Years Follow-Up

“…As recommended by other authors [23]. Caring for individuals with FA, the scales were administered in a single, one-hour session, to minimize the effects of fatigue and thereby maximize accuracy.…”

“…Furthermore, this treatment had the usual objectives of a physical program in such patients [23][24][25][26]. Specifically, the objective of each physical session was to develop the patients' functional capacity (aerobic capacity, flexibility, upper and lower limb strength, motor coordination and balance).…”

Childhood Ataxia

“…The study found no evidence that idebenone improved exercise capacity relative to placebo. 28 Exercise has been advised for patients with neuromuscular diseases. In 1986 at the Sixth International Congress of Neuromuscular Disease, Perlman described an exercise study where out of the 20 patients participating, all 10 patients with Friedreich ataxia were more likely to improve or stabilize after a 2-year home exercise program.…”