Phase III Trial of Coenzyme Q10 in Mitochondrial Disease

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.

Inclusion Criteria:

- Age 12 m - 17 y

- Biochemical proof of a deficiency of complex I, III or IV of the RC or a molecular
genetic proof of a mutation in mtDNA, or an nDNA mutation in a gene known to be
associated with dysfunction of the electron transport chain (e.g., SURF1)

- Willingness to stop all other medication regimens and supplements other than what the
Steering and Planning Committee deems medically necessary

Exclusion Criteria:

- A genetic mitochondrial disease other than those stipulated under inclusion criteria

- Intractable epilepsy, defined as grand mal seizures occurring with a frequency >
4/month, despite treatment with conventional antiepileptic drugs

- Primary, defined organic acidurias other than lactic acidosis (e.g., propionic
aciduria

- Primary disorders of amino acid metabolism

- Primary disorders of fatty acid oxidation

- Secondary lactic acidosis due to impaired oxygenation or circulation (e.g., due to
severe cardiomyopathy or congenital heart defects)

- Severe anemia, defined as a hematocrit <30%

- Malabsorption syndromes associated with D-lactic acidosis

- Renal insufficiency, defined as (1) a requirement for chronic dialysis or (2) serum
creatinine ≥ 1.2 mg/dl or creatinine clearance <60 ml/min

- Primary hepatic disease unrelated to mitochondrial disease

- Allergy to CoQ10 or placebo ingredients

- Pregnancy