Trial record 1 of 1 for:    NCT00432744.
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Phase III Trial of Coenzyme Q10 in Mitochondrial Disease

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT00432744
First received: February 6, 2007
Last updated: April 30, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Mitochondrial Diseases
Drug: CoenzymeQ10
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Phase 3 Trial of Coenzyme Q10 in Mitochondrial Disease

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • McMaster Gross Motor Function (GMFM 88) [ Time Frame: Taken at 6 and 12 Months ] [ Designated as safety issue: No ]
    The McMaster Gross Motor Function is a validated scale ranging from 0 to 100 (the higher the better). Since there was the possibility of a subject becoming totally disabled our FDA peer reviewed design called for its use as follows: If the subject completed both periods, the score was calculated as the difference in scores between the end of Period 2 (at 12 months) minus that at the end of Period 1 (6 months). If a subject became totally disabled, this difference was considered as plus infinity if it occurred in period 1 (Penalizes period 1), and minus infinity if it occurred in Period 2 (Penalizes period 2). The two treatments were compared via the Wilcoxon test, and the effect size was estimated using Kendall's Tau-B. This is interpreted in a similar manner to correlation with positive values favoring COQenzyme10 and negative values favoring placebo. One of the links in this report is to the the GMFM scale and how it is scored. A link to the instrument is included.

  • Pediatric Quality of Life Scale [ Time Frame: At 6 and 12 Months ] [ Designated as safety issue: No ]
    The Pediatric Quality of Life Scale is a validated scale ranging from 0 to 100 (the higher the better). Since there was the possibility of a subject becoming totally disabled our FDA peer reviewed design called for its use as follows: If the subject completed both periods, the score was calculated as the difference in scores between the end of Period 2 (at 12 months) minus that at the end of Period 1 (6 months). If a subject became totally disabled, this difference was considered as plus infinity if it occurred in period 1 (Penalizes period 1), and minus infinity if it occurred in Period 2 (Penalizes period 2). The two treatments were compared via the Wilcoxon test, and the effect size was estimated using Kendall's Tau-B. This is interpreted in a similar manner to correlation with positive values favoring COQenzyme10 and negative values favoring placebo. Goggle "pedsQL and Mapi" to browse the copyrighted manual. A link to the instrument is included.

  • Non-parametric Hotelling T-square Bivariate Analysis of GMGF 88 and OPeds QOL. [ Time Frame: end of 12 month minus end of 6 month difference. ] [ Designated as safety issue: No ]
    This is a multivariate analysis of the first two outcomes: Period 2 minus Period 1 GMFM88 and Peds Quality of Life, analyzed as follows: First, to be in the analysis, subjects must contribute at least one of these endpoints. Second, if the subject became totally disabled during period 1, the difference was defined as + infinity, (highest possible evidence favoring period 2), and if the subject became totally disabled in period 2, the subject was scored as - infinity (highest possible evidence favoring period 1). Period 2 minus period 1 differences were ranked form low to high with missing values scores at the mid-rank. The Hotelling T-square was computed on these ranks and the P-value was obtained from 100,000 rerandomizations as the fraction of rerandomizations with T-sq at least as large as that observed.


Enrollment: 24
Study Start Date: January 2007
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: CoenzymeQ10
CoenzymeQ10: patients will be randomized to receive CoenzymeQ10 in either Period #1 (Months 0-6) or Period #2 (Months 7-12).
Drug: CoenzymeQ10
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.
Other Name: CoenzymeQ10
Placebo Comparator: Placebo
Placebo: patients will be randomized to receive placebo either ion Period #1 (months 1-6) or Period #2 (months 7-12).
Drug: Placebo
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.
Other Name: Placebo

  Hide Detailed Description

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.

  Eligibility

Ages Eligible for Study:   12 Months to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00432744

Locations
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45267
Case Western Reserve University
Cleveland, Ohio, United States, 44106
Canada, Ontario
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Sponsors and Collaborators
University of Florida
Investigators
Principal Investigator: Douglas S. Kerr, MD, PhD Case Western Reserve University
Principal Investigator: Ton J deGrauw, MD, PhD Children's Hospital Medical Center, Cincinnati
Principal Investigator: Annette S. Feigenbaum, MD SickKids, Toronto, Canada/University of Toronto
  More Information

Additional Information:
Publications:
Kerr DS. Treatment of congenital lactic acidosis: a review. Intern Pediatr, 1995;10:75-81.

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT00432744     History of Changes
Other Study ID Numbers: 1 R01 FD003032-01A1
Study First Received: February 6, 2007
Results First Received: April 11, 2014
Last Updated: April 30, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Florida:
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

Additional relevant MeSH terms:
Mitochondrial Diseases
Metabolic Diseases
Coenzyme Q10
Growth Substances
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs
Vitamins

ClinicalTrials.gov processed this record on October 21, 2014