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

Sponsor:	University of Florida
Collaborator:	FDA Office of Orphan Products Development
Information provided by (Responsible Party):	University of Florida
ClinicalTrials.gov Identifier:	NCT00432744

Purpose

Our central hypothesis is 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 and in quality of life.

Condition	Intervention	Phase
Mitochondrial Diseases	Drug: CoenzymeQ10 Drug: Coenzyme Q10 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

Resource links provided by NLM:

Genetics Home Reference related topics: ataxia neuropathy spectrum childhood myocerebrohepatopathy spectrum myoclonic epilepsy myopathy sensory ataxia Help Me Understand Genetics

Drug Information available for: Ubidecarenone

U.S. FDA Resources

Further study details as provided by University of Florida:

Primary Outcome Measures:

Gross motor function and [ Time Frame: Every six months ] [ Designated as safety issue: No ]
home quality of life (QOL) [ Time Frame: Monthly ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

diagnostic laboratory data; [ Time Frame: Every three months ] [ Designated as safety issue: Yes ]
H&P: patient demographic information and pertinent physiologic measures; [ Time Frame: Every three months ] [ Designated as safety issue: Yes ]
motor assessments: Gross Motor Function Measure, [ Time Frame: Every six months ] [ Designated as safety issue: No ]
neurobehavioral assessments: NIHM neurobehavioral examination, the Child Development Inventory and the American Association on Mental Retardation Adaptive Behavior Scales; [ Time Frame: Every six months ] [ Designated as safety issue: No ]
QOL assessment; [ Time Frame: Every three months ] [ Designated as safety issue: No ]
sleep questionnaire; [ Time Frame: Every three months ] [ Designated as safety issue: No ]
CoQ10 profile data; [ Time Frame: Once upon entrance into trial ] [ Designated as safety issue: No ]
LiQ-nol parent survey Effects Report and [ Time Frame: Every three months ] [ Designated as safety issue: Yes ]
QOL Validity Studies [ Time Frame: Every three months ] [ Designated as safety issue: No ]

Estimated Enrollment:	50
Study Start Date:	January 2007
Estimated Study Completion Date:	May 2013
Estimated Primary Completion Date:	May 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 Draw CoQ10 troughs every three months	Drug: CoenzymeQ10 Draw CoQ10 troughs every three months Drug: Coenzyme Q10 10 mg/k daily up to 400 mg
Placebo Comparator: 2 Placebo	Drug: Placebo Placebo daily

Detailed Description:

This postulate will be tested by accomplishing the following specific aims:

Specific Aim 1. Conduct a multicenter, prospective, randomized, double-blind, placebo controlled crossover trial of oral CoQ10 in children with biochemically proven deficiencies of complex I, III or IV of the RC or with mutations of a gene coding for an RC component (mtDNA and nDNA). This aim tests the hypothesis that supplementation with CoQ10 (10 mg/kg/d) is safe and more effective in improving outcome than placebo. General Clinical Research Centers (GCRCs) or similar facilities will be the venues for this phase 3 clinical trial.

Specific Aim 2. Determine the effectiveness of CoQ10 in improving the morbidity of affected patients. This aim addresses the postulate that high dose CoQ10 improves quality of life and motor function as determined by a validated questionnaire for this patient population, and by objective, standardized measures of motor function.

Specific Aim 3. Determine the safety of CoQ10 in the target population. This aim tests the postulate that the formulation and dose of CoQ10 employed is well tolerated and the administration of this product is not associated with significantly more numerous or more severe adverse events than is administration of placebo.

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

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

Contacts

Contact: Peter W Stacpoole, PhD, MD	352/392-2321	peter.stacpoole@medicine.ufl.edu
Contact: Tracie L Kurtz, RN	(888) 961-9068	tracie.kurtz@medicine.ufl.edu

Locations

United States, Ohio
Cincinnati Children's Hospital Medical Center	Recruiting
Cincinnati, Ohio, United States, 45267
Contact: Ton J deGrauw, MD, PhD 513-636-8680 t.degrauw@cchmc.org
Contact: Prajakta Mangeshkar, RN (513) 636-8016 prajakta.mangeshkar@cchmc.org
Principal Investigator: Ton J deGrauw, MD, PhD
Case Western Reserve University	Recruiting
Cleveland, Ohio, United States, 44106
Contact: Shawn McCandless, MD 216-844-1612 sxm32@case.edu
Contact: Mary Beth Frohnapfel, RN (216) 844-0343 marybeth.frohnapfel@Uhhospitals.com
Principal Investigator: Douglas S. Kerr, MD, PhD
Canada, Ontario
Hospital for Sick Children	Recruiting
Toronto, Ontario, Canada, M5G 1X8
Contact: Annette S. Feigenbaum, MD (416) 813-5340 annette.feigenbaum@sickkids.ca
Contact: Mohammed Hussain (416) 813-7654 ext 2646 mohammed.hussain@sickkids.ca
Principal Investigator: Annette S. Feigenbaum, MD

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 General Clinical Research Center 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:	1 R01 FD003032-01A1
Study First Received:	February 6, 2007
Last Updated:	March 19, 2012
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
Pharmacologic Actions
Vitamins

ClinicalTrials.gov processed this record on May 22, 2012