• Gross motor function and [ Time Frame: Every six months ] [ Designated as safety issue: No ]
• home quality of life (QOL) [ Time Frame: Monthly ] [ Designated as safety issue: No ]

• Gross motor function and
• home quality of life (QOL)

• diagnostic laboratory data; [ Time Frame: Every three months ] [ Designated as safety issue: Yes ]
• H&P: patient demographic information and pertinent physiologic measures; [ Time Frame: Every three months ] [ Designated as safety issue: Yes ]
• motor assessments: Gross Motor Function Measure, [ Time Frame: Every six months ] [ Designated as safety issue: No ]
• neurobehavioral assessments: NIHM neurobehavioral examination, the Child Development Inventory and the American Association on Mental Retardation Adaptive Behavior Scales; [ Time Frame: Every six months ] [ Designated as safety issue: No ]
• QOL assessment; [ Time Frame: Every three months ] [ Designated as safety issue: No ]
• sleep questionnaire; [ Time Frame: Every three months ] [ Designated as safety issue: No ]
• CoQ10 profile data; [ Time Frame: Once upon entrance into trial ] [ Designated as safety issue: No ]
• LiQ-nol parent survey Effects Report and [ Time Frame: Every three months ] [ Designated as safety issue: Yes ]
• QOL Validity Studies [ Time Frame: Every three months ] [ Designated as safety issue: No ]

• diagnostic laboratory data;
• H&P: patient demographic information and pertinent physiologic measures;
• motor assessments: Gross Motor Function Measure,
• neurobehavioral assessments: NIHM neurobehavioral examination, the Child Development Inventory and the American Association on Mental Retardation Adaptive Behavior Scales;
• QOL assessment;
• sleep questionnaire;
• CoQ10 profile data;
• LiQ-nol parent survey Effects Report and
• QOL Validity Studies

Our central hypothesis is that oral CoQ10 is a safe and effective treatment for children with inborn errors of mitochondrial energy metabolism due to defects in specific respiratory chain (RC) complexes or mitochondrial DNA (mtDNA) mutations, and that this beneficial action is reflected in improved motor and neurobehavioral 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.

• Drug: CoenzymeQ10
• Drug: Coenzyme Q10
• Drug: Placebo

• Active Comparator: Draw CoQ10 troughs every three months
• Placebo Comparator: Placebo

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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