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Phase III Trial of Coenzyme Q10 in Mitochondrial Disease

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ClinicalTrials.gov Identifier: NCT00432744
Recruitment Status : Completed
First Posted : February 8, 2007
Results First Posted : May 1, 2014
Last Update Posted : September 11, 2017
Sponsor:
Collaborators:
FDA Office of Orphan Products Development
Food and Drug Administration
Information provided by (Responsible Party):
University of Florida

Study Description
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Brief 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.

Condition or disease Intervention/treatment Phase
Mitochondrial Diseases Drug: CoenzymeQ10 Drug: Placebo Phase 3

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Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Phase 3 Trial of Coenzyme Q10 in Mitochondrial Disease
Study Start Date : January 2007
Actual Primary Completion Date : May 2013
Actual Study Completion Date : May 2013

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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.
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.


Outcome Measures
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Primary Outcome Measures :
  1. McMaster Gross Motor Function (GMFM 88) [ Time Frame: Taken at 6 and 12 Months ]
    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.

  2. Pediatric Quality of Life Scale [ Time Frame: At 6 and 12 Months ]
    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.

  3. 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. ]
    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.


Eligibility Criteria
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Ages Eligible for Study:   12 Months to 17 Years   (Child)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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
FDA Office of Orphan Products Development
Food and Drug Administration
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
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Additional Information:
University of Florida Clinical Research Center, Clinical and Translational Science Institute  This link exits the ClinicalTrials.gov site
Describes the 23 item Pediatric Quality of Life  This link exits the ClinicalTrials.gov site

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: 1R01FD003032-01A1 ( U.S. FDA Grant/Contract )
R01FD003032-01A1 ( U.S. FDA Grant/Contract )
First Posted: February 8, 2007    Key Record Dates
Results First Posted: May 1, 2014
Last Update Posted: September 11, 2017
Last Verified: September 2017

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
Ubiquinone
 Micronutrients
Growth Substances
Physiological Effects of Drugs
Vitamins