EPI-743 for Metabolism or Mitochondrial Disorders
Mitochondrial Disease, Neurology, Myopathy
About this trial
This is an interventional treatment trial for Mitochondrial Disease focused on measuring Oxidative Stress, Oxidative Phosphorylation, Mitochondrial Disease
Eligibility Criteria
- INCLUSION CRITERIA:
Inclusion criteria involve enrollment in protocol 76-HG-0238, Diagnosis and Treatment of Patients with Inborn Errors of Metabolism and Other Genetic Disorders . In addition, patients must:
- Be 2-11 years of age
- Manifest clinical findings of a neuromuscular disease with a component of impaired energy or oxidation/reduction. Typical symptoms would include hypotonia, dystonia, or seizures.
- Have a disorder that is untreatable or poorly treatable.
- Have cultured fibroblasts that exhibit reduced viability under conditions of oxidative stress, compared to age matched control fibroblasts.
- Have cultured fibroblasts that achieve at least 80% viability rescue with EPI-743 at 1micromolar upon exposure to oxidative stress and that have a half maximal effective concentration of EPI-743 of less than or equal to 50 nanomolar.
- Be willing to abstain from initiating the use of dietary supplements and nonprescribed medications, foods or beverages or bars fortified with coenzyme Q(10), vitamin E, super fortified functional foods or beverages, and idebenone.
- Be able to travel to the Clinical Center for at least 8 visits.
EXCLUSION CRITERIA:
- Age < 2 years or >11 years
- Diagnosis of mitochondrial diseases benefiting from treatment and at risk from being moved to placebo
- Allergy to EPI-743 or sesame oil
- Hepatic insufficiency with liver function tests greater than 3-times the upper limit of normal
- Renal insufficiency requiring dialysis
- Significant malabsorption of fats precluding drug absorption
- Allergy to vitamin E
- Significant coagulation abnormalities as evidenced by abnormal PT/PTT tests
- Severe end-organ hypo-perfusion syndrome secondary to cardiac failure resulting in lactic acidosis
- Ventilator-dependence
- Chronic pancreatitis
- Clinical history of bleeding requiring ongoing medical management
- Abnormal red cell parameters requiring ongoing medical management besides iron supplementation
- A platelet disorder
- Neutrophils less than 500 mm3
Sites / Locations
- National Institutes of Health Clinical Center, 9000 Rockville Pike
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
EPI-743, then Placebo
Placebo, then EPI-743
Received EPI-743, 15mg/kg up to a maximum dose of 200 mg orally or via gastric tube three times daily with meals, then placebo three times daily orally or via gastric tube with meals. EPI-743 is structurally related to Vitamin E and can be broadly classified as an antioxidant.
Received Placebo three times daily orally or via gastric tube with meals, then EPI-743, 15mg/kg up to a maximum dose of 200 mg three times daily orally or via gastric tube with meals. EPI-743 is structurally related to Vitamin E and can be broadly classified as an antioxidant.