Treatment of mitochondrial diseases has been generally disappointing and has usually been approached in an uncontrolled manner. Although there is no proven therapy for any congenital mitochondrial disease, CoQ10 is a potential treatment for specific deficiencies of the respiratory chain, because of its apparent safety, its integral role in the processes of electron transport and cellular energetics and its antioxidative properties. The investigators postulate that CoQ10 is a safe and effective treatment for children with inborn errors of mitochondrial energetics due to defects in specific respiratory chain (RC) complexes or mitochondrial DNA (mtDNA) mutations, and that this beneficial action will be reflected in improved motor function and in quality of life. This postulate will be tested by accomplishing the following specific aims:
Specific Aim 1. Conduct a multicenter, prospective, randomized, double-blind, placebo controlled crossover trial of oral CoQ10 in children with biochemically proven deficiencies of complex I, III or IV of the RC or with mutations of a gene coding for an RC component (mtDNA and nDNA).
This aim tests the hypothesis that supplementation with CoQ10 (10 mg/kg/d) is safe and more effective in improving outcome than placebo. General Clinical Research Centers (GCRCs) or similar facilities will be the venues for this Phase 3 clinical trial.
Specific Aim 2. Determine the effectiveness of CoQ10 in improving the morbidity of affected patients.
This aim addresses the postulate that high dose CoQ10 improves quality of life and motor function as determined by a validated questionnaire for this patient population, and by objective, standardized measures of motor function.
Specific Aim 3. Determine the safety of CoQ10 in the target population.
This aim tests the postulate that the formulation and dose of CoQ10 employed is well tolerated and the administration of this product is not associated with significantly more numerous or more severe adverse events than is administration of placebo. This controlled trial of oral CoQ10 in children with congenital RC defects or mtDNA mutations should provide important insight into the future role of this cofactor in treating inborn errors of mitochondrial energy metabolism. Furthermore, the multicenter collaboration should provide a model for future clinical trials in this clinical population.
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