Phase III Trial of Coenzyme Q10 in Mitochondrial Disease - Full Text View

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:

Genetics Home Reference related topics: ataxia neuropathy spectrum childhood myocerebrohepatopathy spectrum cytochrome c oxidase deficiency deoxyguanosine kinase deficiency mitochondrial neurogastrointestinal encephalopathy disease myoclonic epilepsy myopathy sensory ataxia

MedlinePlus related topics: Mitochondrial Diseases

Drug Information available for: Ubidecarenone

U.S. FDA Resources

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.
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.

Show Detailed Description

Eligibility


Ages Eligible for Study:	12 Months to 17 Years (Child)
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

FDA Office of Orphan Products Development

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:

University of Florida Clinical Research Center, Clinical and Translational Science Institute This link exits the ClinicalTrials.gov site

Publications:

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Responsible Party:	University of Florida
ClinicalTrials.gov Identifier:	NCT00432744 History of Changes
Other Study ID Numbers:	1R01FD003032-01A1
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 Ubiquinone	Micronutrients Growth Substances Physiological Effects of Drugs Vitamins

ClinicalTrials.gov processed this record on September 29, 2016