Design and implementation of the first randomized controlled trial of coenzyme Q10 in children with primary mitochondrial diseases

Abstract

We report the design and implementation of the first phase 3 trial of CoenzymeQ10 (CoQ10) in children with genetic mitochondrial diseases. A novel, rigorous set of eligibility criteria was established. The trial, which remains open to recruitment, continues to address multiple challenges to the recruitment of patients, including widely condoned empiric use of CoQ10 by individuals with proven or suspected mitochondrial disease and skepticism among professional and lay mitochondrial disease communities about participating in placebo-controlled trials. These attitudes represent significant barriers to the ethical and scientific evaluation–and ultimate approval–of nutritional and pharmacological therapies for patients with life-threatening inborn errors of energy metabolism.

Muscle oxidative phosphorylation quantitation using creatine chemical exchange saturation transfer (CrCEST) MRI in mitochondrial disorders

“…We prioritized eligible subjects with disorders confirmed to be caused by pathogenic mitochondrial DNA or nuclear DNA mutations affecting subunits or assembly of mitochondrial respiratory chain complexes that are associated with known clinical/pathological features. These disorders include CPEO; Kearns-Sayre syndrome; MELAS; mitochondrial encephalopathy and ragged red fibers (MERRF); neuropathy, ataxia and retinitis pigmentosa (NARP); or Leigh syndrome (44). Individuals affected with FA were also studied.…”

Mitochondrial dysfunction in cardiac aging

“…Mouse studies involving ApoA1 −/− mice demonstrate that addition of CoQ10 improves infarct size to that of a wild-type mouse [213]. Current human studies using CoQ10 in dietary supplements in adults have hint at improved health with an optimal diet [214, 215], and clinical study in children with primary mitochondrial diseases is underway[214, 215]. …”

Review of Clinical Trials for Mitochondrial Disorders: 1997–2012

“…A phase III, placebo-controlled, double-blind, randomized, multicentered trial of CoQ 10 in children and adolescents with mitochondrial disorders has been in progress for the past few years, based at the University of Florida, which is not yet completed [26]. Design of this study is to administer ubiquinol (LiQnol®) 10 mg/kg d (up to 400 mg) or placebo for 6 months, followed by crossover to the alternative agent for another 6 months ( Table 1).…”

“…Secondary outcome measures are a standard neurological examination, Child Development Inventory, and plasma CoQ 10 levels. Eligibility criteria for patients include a well-characterized deficiency of one or more ETC complexes with evidence of sample integrity, or a pathogenic mutation affecting ETC or oxidative phosphorylation, and associated phenotypic features of a mitochondrial disorder [26].…”