Mitochondrial DiseasesPhase 3NCT00432744
Phase III Trial of Coenzyme Q10 in Mitochondrial Disease
A Phase 3 study testing CoenzymeQ10 in people with Mitochondrial Diseases, run by University of Florida at 3 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 months to 17 years
- Conditions the study is for
- Mitochondrial Diseases
- What is being tested?
- CoenzymeQ10
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Jan 2007to May 2013
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 months to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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)
Show all 12Show fewer
- 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
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
United States2 sites
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45267
Case Western Reserve University
Cleveland, Ohio, 44106
About this study
Official title: Phase 3 Trial of Coenzyme Q10 in Mitochondrial Disease
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.
Read the 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.
- Conditions
- Mitochondrial Diseases
- Being tested
- CoenzymeQ10, Placebo
- 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
- Medical subject headings
- Mitochondrial Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CoenzymeQ10Drug
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| CoenzymeQ10 | Active comparator | CoenzymeQ10: patients will be randomized to receive CoenzymeQ10 in either Period #1 (Months 0-6) or Period #2 (Months 7-12). Receives: Drug: CoenzymeQ10 |
| Placebo | Placebo comparator | Placebo: patients will be randomized to receive placebo either ion Period #1 (months 1-6) or Period #2 (months 7-12). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
McMaster Gross Motor Function (GMFM 88)
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.
Measured: Taken at 6 and 12 Months
Pediatric Quality of Life Scale
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.
Measured: At 6 and 12 Months
Non-parametric Hotelling T-square Bivariate Analysis of GMGF 88 and OPeds QOL.
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.
Measured: end of 12 month minus end of 6 month difference.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2007 (estimated)
- Study startJan 2007
- Primary completionMay 2013
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (26)Papers the sponsor has linked to this study.
- Other trials for Mitochondrial DiseasesStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- FDA Office of Orphan Products Development, Food and Drug Administration (FDA)
- Responsible party
- Sponsor
- Investigators
- Douglas S. Kerr, MD, PhD, Principal investigator, Case Western Reserve UniversityTon J deGrauw, MD, PhD, Principal investigator, Children's Hospital Medical Center, CincinnatiAnnette S. Feigenbaum, MD, Principal investigator, SickKids, Toronto, Canada/University of Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00432744
- Sponsor's protocol ID
- 1R01FD003032-01A1
- Other IDs
- R01FD003032-01A1
- Status last verified
- Sep 2017
- First submitted
- 6 Feb 2007
- Last updated
- 11 Sep 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Hanna MG, Nelson IP. Genetics and molecular pathogenesis of mitochondrial respiratory chain diseases. Cell Mol Life Sci. 1999 May;55(5):691-706. doi: 10.1007/s000180050327.
PubMed 10379358Kerr DS. Treatment of congenital lactic acidosis: a review. Intern Pediatr, 1995;10:75-81.
Abe K, Fujimura H, Nishikawa Y, Yorifuji S, Mezaki T, Hirono N, Nishitani N, Kameyama M. Marked reduction in CSF lactate and pyruvate levels after CoQ therapy in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Acta Neurol Scand. 1991 Jun;83(6):356-9. doi: 10.1111/j.1600-0404.1991.tb03962.x.
PubMed 1887756Ogasahara S, Nishikawa Y, Yorifuji S, Soga F, Nakamura Y, Takahashi M, Hashimoto S, Kono N, Tarui S. Treatment of Kearns-Sayre syndrome with coenzyme Q10. Neurology. 1986 Jan;36(1):45-53. doi: 10.1212/wnl.36.1.45.
PubMed 3941783Gold R, Seibel P, Reinelt G, Schindler R, Landwehr P, Beck A, Reichmann H. Phosphorus magnetic resonance spectroscopy in the evaluation of mitochondrial myopathies: results of a 6-month therapy study with coenzyme Q. Eur Neurol. 1996;36(4):191-6. doi: 10.1159/000117246.
PubMed 8814419Matthews PM, Ford B, Dandurand RJ, Eidelman DH, O'Connor D, Sherwin A, Karpati G, Andermann F, Arnold DL. Coenzyme Q10 with multiple vitamins is generally ineffective in treatment of mitochondrial disease. Neurology. 1993 May;43(5):884-90. doi: 10.1212/wnl.43.5.884.
PubMed 8492942Bresolin N, Doriguzzi C, Ponzetto C, Angelini C, Moroni I, Castelli E, Cossutta E, Binda A, Gallanti A, Gabellini S, et al. Ubidecarenone in the treatment of mitochondrial myopathies: a multi-center double-blind trial. J Neurol Sci. 1990 Dec;100(1-2):70-8. doi: 10.1016/0022-510x(90)90015-f.
PubMed 2089142Shults CW, Oakes D, Kieburtz K, Beal MF, Haas R, Plumb S, Juncos JL, Nutt J, Shoulson I, Carter J, Kompoliti K, Perlmutter JS, Reich S, Stern M, Watts RL, Kurlan R, Molho E, Harrison M, Lew M; Parkinson Study Group. Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol. 2002 Oct;59(10):1541-50. doi: 10.1001/archneur.59.10.1541.
PubMed 12374491Ogasahara S, Engel AG, Frens D, Mack D. Muscle coenzyme Q deficiency in familial mitochondrial encephalomyopathy. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2379-82. doi: 10.1073/pnas.86.7.2379.
PubMed 2928337Musumeci O, Naini A, Slonim AE, Skavin N, Hadjigeorgiou GL, Krawiecki N, Weissman BM, Tsao CY, Mendell JR, Shanske S, De Vivo DC, Hirano M, DiMauro S. Familial cerebellar ataxia with muscle coenzyme Q10 deficiency. Neurology. 2001 Apr 10;56(7):849-55. doi: 10.1212/wnl.56.7.849.
PubMed 11294920Lamperti C, Naini A, Hirano M, De Vivo DC, Bertini E, Servidei S, Valeriani M, Lynch D, Banwell B, Berg M, Dubrovsky T, Chiriboga C, Angelini C, Pegoraro E, DiMauro S. Cerebellar ataxia and coenzyme Q10 deficiency. Neurology. 2003 Apr 8;60(7):1206-8. doi: 10.1212/01.wnl.0000055089.39373.fc.
PubMed 12682339Rahman S, Hargreaves I, Clayton P, Heales S. Neonatal presentation of coenzyme Q10 deficiency. J Pediatr. 2001 Sep;139(3):456-8. doi: 10.1067/mpd.2001.117575.
PubMed 11562630Argov Z, Bank WJ, Maris J, Eleff S, Kennaway NG, Olson RE, Chance B. Treatment of mitochondrial myopathy due to complex III deficiency with vitamins K3 and C: A 31P-NMR follow-up study. Ann Neurol. 1986 Jun;19(6):598-602. doi: 10.1002/ana.410190615.
PubMed 3014998Geromel V, Darin N, Chretien D, Benit P, DeLonlay P, Rotig A, Munnich A, Rustin P. Coenzyme Q(10) and idebenone in the therapy of respiratory chain diseases: rationale and comparative benefits. Mol Genet Metab. 2002 Sep-Oct;77(1-2):21-30. doi: 10.1016/s1096-7192(02)00145-2.
PubMed 12359126Beal MF. Mitochondria, oxidative damage, and inflammation in Parkinson's disease. Ann N Y Acad Sci. 2003 Jun;991:120-31. doi: 10.1111/j.1749-6632.2003.tb07470.x.
PubMed 12846981
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 3 Trial of Coenzyme Q10 in Mitochondrial Disease
- ClinicalTrials.gov ID
- NCT00432744
- Acronym / sponsor ID
- 1R01FD003032-01A1
- Conditions
- Mitochondrial Diseases
- 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
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- FDA Office of Orphan Products Development, Food and Drug Administration (FDA)
- Study start
- Jan 2007
- Primary completion
- May 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 8 Feb 2007 (estimated)
- Results
- Posted 1 May 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CoenzymeQ10 | Active comparator | Drug: CoenzymeQ10CoenzymeQ10: patients will be randomized to receive CoenzymeQ10 in either Period #1 (Months 0-6) or Period #2 (Months 7-12). |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo: patients will be randomized to receive placebo either ion Period #1 (months 1-6) or Period #2 (months 7-12). |
Who may qualify
- Ages
- 12 months to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CoenzymeQ10CoenzymeQ10 will be given in 10 mg/kg daily up to 400 mg. Then a draw of CoQ10 troughs every three months will be performed. | Drug | CoenzymeQ10 |
| PlaceboPlacebo 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. | Drug | Placebo |
Primary outcome
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.
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 10379358Hanna MG, Nelson IP. Genetics and molecular pathogenesis of mitochondrial respiratory chain diseases. Cell Mol Life Sci. 1999 May;55(5):691-706. doi: 10.1007/s000180050327.
- BackgroundKerr DS. Treatment of congenital lactic acidosis: a review. Intern Pediatr, 1995;10:75-81.
- Background: PubMed 1887756Abe K, Fujimura H, Nishikawa Y, Yorifuji S, Mezaki T, Hirono N, Nishitani N, Kameyama M. Marked reduction in CSF lactate and pyruvate levels after CoQ therapy in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Acta Neurol Scand. 1991 Jun;83(6):356-9. doi: 10.1111/j.1600-0404.1991.tb03962.x.
- Background: PubMed 3941783Ogasahara S, Nishikawa Y, Yorifuji S, Soga F, Nakamura Y, Takahashi M, Hashimoto S, Kono N, Tarui S. Treatment of Kearns-Sayre syndrome with coenzyme Q10. Neurology. 1986 Jan;36(1):45-53. doi: 10.1212/wnl.36.1.45.
- Background: PubMed 8814419Gold R, Seibel P, Reinelt G, Schindler R, Landwehr P, Beck A, Reichmann H. Phosphorus magnetic resonance spectroscopy in the evaluation of mitochondrial myopathies: results of a 6-month therapy study with coenzyme Q. Eur Neurol. 1996;36(4):191-6. doi: 10.1159/000117246.
- Background: PubMed 8492942Matthews PM, Ford B, Dandurand RJ, Eidelman DH, O'Connor D, Sherwin A, Karpati G, Andermann F, Arnold DL. Coenzyme Q10 with multiple vitamins is generally ineffective in treatment of mitochondrial disease. Neurology. 1993 May;43(5):884-90. doi: 10.1212/wnl.43.5.884.
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- University of Florida Clinical Research Center, Clinical and Translational Science InstituteLink provided by the sponsor.
- Describes the 23 item Pediatric Quality of LifeLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Douglas S. Kerr, MD, PhD principal investigator
Case Western Reserve University
Ton J deGrauw, MD, PhD principal investigator
Children's Hospital Medical Center, Cincinnati
Annette S. Feigenbaum, MD principal investigator
SickKids, Toronto, Canada/University of Toronto
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing CoenzymeQ10 in people with Mitochondrial Diseases, run by University of Florida at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
McMaster Gross Motor Function (GMFM 88) (time frame: Taken at 6 and 12 Months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00432744, which also lists 26 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2017; AzTrials last refreshed its copy on 8 Nov 2026.