Phase III Trial of Coenzyme Q10 in Mitochondrial Disease
Condition: Mitochondrial Diseases
MeSH terms: Mitochondrial Diseases
Study type: Interventional
Phase: Phase 3

Summary: 
      To show 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.
    

Detailed description: 
      In many patients mitochondrial disease leads to progressive nerve and muscle damage that may
      be associated with problems with thinking, talking, remembering, walking or balancing.
      Sometimes it may also cause abnormal build up in the blood and spinal fluid of a substance
      called lactic acid. This problem makes the blood and spinal fluid too acid, which can be
      life-threatening. There is no known specific or effective treatment for mitochondrial
      diseases. Sometimes certain diets can improve the condition but seldom prevent the nerve or
      muscle damage or reduce the chance of developing life-threatening acidity of the blood.

      CoQ10 is not approved by the Food and Drug Administration (FDA) for the treatment of
      mitochondrial diseases. It is an investigational drug that we believe may help people with
      certain mitochondrial diseases, like the one you have, both in terms of reducing the acidity
      of your blood and preventing or decreasing nerve and muscle damage. Our belief is based on
      previous studies that have been conducted in children with mitochondrial diseases of various
      types. Therefore, a 12 month study has been designed to determine the safety and benefit of
      taking CoQ10 every day. This will be done by comparing the subjects response to taking CoQ10
      for 6 months to taking a placebo for 6 months. A placebo looks, smells, and tastes like the
      drug being tested (in this case, CoQ10) but has no effect. Placebo studies such as this one
      are very common in evaluating investigational drugs for any disease and are usually required
      by the FDA before a drug can be approved.

      CoQ10 or placebo will be given as a liquid once per day in the evening, by mouth or feeding
      tube. The CoQ10 dose will be 10 mg/kg with a maximum dose of 400 mg a day. Neither the
      subject nor the health care givers will know exactly when subjects are receiving CoQ10 or
      when subjects are receiving the placebo. However, subjects will receive CoQ10 for at least 6
      months. At each visit the subject will be given a seven month supply of CoQ10, nutritional
      cocktail, and multivitamins to take home and they will be asked to bring back any unused
      medications at the next visit. At each visit subjects will be given a medication diary to
      record the time and date that they take the medications that will be provided. This diary
      should be returned to the study coordinator at the subject's scheduled visit. During the 12
      month period that subjects are on the study, they will be expected to stop taking all
      medications and other supplements except for those provided by the study and those that the
      study doctor determines are medically needed. Except in the case of an emergency, the subject
      must contact the study doctor before taking any new medications or supplements. In the case
      of an emergency, subjects are required to inform the study doctor of the emergency and
      treatments as soon as possible.

      Subjects will be hospitalized on the General Clinical Research Center (GCRC) ward of Shands
      Hospital for 2-4 days every three to six months. A parent or legal guardian will be expected
      to stay with the subject. During that hospitalization, physical and intellectual development
      will be measured by standard tests. The GCRC dietician will ask questions about current diet
      at each visit and record answers. A general medical history and physical examination
      (including gross motor function and/or strength tests) will be performed during each visit as
      well as a six minute walking test. While enrolled in this study, a special "nutritional
      cocktail" and a Centrum-like multivitamin supplement will be provided for subjects to take
      daily. The nutritional cocktail has vitamin C, up to 10 mg/kg/day (max. 400 mg/day),
      riboflavin, up to 2.5 mg/kg/day (max. 100 mg/day), thiamine, up to 2.5 mg/kg/day (100
      mg/day), carnitine, up to 10 mg/kg/day (max. 400 mg/day). The nutritive cocktail is in
      capsule form and the number of capsules that the subject will take will be based on body
      weight (for every 4 kg. of body weight subjects will receive 1 capsule daily). Each capsule
      contains: Vitamin C 40 mg, Riboflavin 10 mg, thiamine 10 mg and carnitine 40 mg. The maximum
      amount of capsules that will be given daily to anyone in this study is 10 capsules daily. A
      parent or legal guardian will be asked to complete each of eight questionnaires regarding
      behavioral and developmental, quality of life (5), and sleep. The behavioral and
      developmental, four of the quality of life (QOL) questionnaires, and the sleep questionnaire
      should be completed at the 0, 6 and 12 month visits. One of the QOL questionnaires (46
      questions) will need to be completed monthly and mailed back to the study center after
      completion (self-addressed, stamped envelopes will be provided by the study and given to you
      by the coordinator). We expect that it will take up to 20 minutes to complete the monthly QOL
      questionnaire and up to 3 hours at the 0, 6 and 12 month visit to complete the rest of the
      questionnaires.

      About 15-20 ml. of blood (3-4 teaspoons) will be obtained during each hospitalization. A
      urine sample will also be collected during each hospital visit. In females of child-bearing
      age, urine will also be collected and tested for the presence of HCG (a hormone that
      determines pregnancy). Within 24 hours of blood and urine collection test results will be
      assessed by the study physician.
    

Intervention name(s): CoenzymeQ10; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): CoenzymeQ10 will be given in 10 mg/kg daily up to 400 mg. Then a draw of CoQ10 troughs every three months will be performed.; Placebo will be given in 10 mg/kg daily up to 400 mg. Then a draw of placebo troughs every three months will be performed. This treatment group will be treated as the active group.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: mitochondrial diseases; respiratory chain complex I deficiencies; respiratory chain complex II deficiencies; respiratory chain complex III deficiencies; respiratory chain complex IV deficiencies; mutations of a gene coding for a respiratory chain component