Phase III Trial of Coenzyme Q10 in Mitochondrial Disease

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.

Timeline

Start

2007-01

Primary completion

2013-05

Completion

2013-05

Publications

• Background 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.
• Background Kerr DS. Treatment of congenital lactic acidosis: a review. Intern Pediatr, 1995;10:75-81.
• Background 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.
• Background Ogasahara 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 Gold 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 Matthews 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.
• Background Bresolin 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.
• Background Shults 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.
• Background Ogasahara 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.
• Background Musumeci 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.
• Background Lamperti 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.
• Background Rahman 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.
• Background Argov 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.
• Background Geromel 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.
• Background Beal 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.
• Background Turunen M, Olsson J, Dallner G. Metabolism and function of coenzyme Q. Biochim Biophys Acta. 2004 Jan 28;1660(1-2):171-99. doi: 10.1016/j.bbamem.2003.11.012.
• Background Miles MV, Horn PS, Tang PH, Morrison JA, Miles L, DeGrauw T, Pesce AJ. Age-related changes in plasma coenzyme Q10 concentrations and redox state in apparently healthy children and adults. Clin Chim Acta. 2004 Sep;347(1-2):139-44. doi: 10.1016/j.cccn.2004.04.003.
• Background ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002 Jul 1;166(1):111-7. doi: 10.1164/ajrccm.166.1.at1102. No abstract available.
• Background Cerveri I, Fanfulla F, Zoia MC, Manni R, Tartara A. Sleep disorders in neuromuscular diseases. Monaldi Arch Chest Dis. 1993 Aug;48(4):318-21.
• Background Johnston K, Newth CJ, Sheu KF, Patel MS, Heldt GP, Schmidt KA, Packman S. Central hypoventilation syndrome in pyruvate dehydrogenase complex deficiency. Pediatrics. 1984 Dec;74(6):1034-40.
• Background Kotagal S, Archer CR, Walsh JK, Gomez C. Hypersomnia, bithalamic lesions, and altered sleep architecture in Kearns-Sayre syndrome. Neurology. 1985 Apr;35(4):574-7. doi: 10.1212/wnl.35.4.574.
• Background Pronicka E, Piekutowska-Abramczuk DH, Popowska E, Pronicki M, Karczmarewicz E, Sykut-Cegielska Y, Taybert J. Compulsory hyperventilation and hypocapnia of patients with Leigh syndrome associated with SURF1 gene mutations as a cause of low serum bicarbonates. J Inherit Metab Dis. 2001 Dec;24(7):707-14. doi: 10.1023/a:1012937204315.
• Background Sakaue S, Ohmuro J, Mishina T, Miyazaki H, Yamaguchi E, Nishimura M, Fujita M, Nagashima K, Tagami S, Kawakami Y. A case of diabetes, deafness, cardiomyopathy, and central sleep apnea: novel mitochondrial DNA polymorphisms. Tohoku J Exp Med. 2002 Mar;196(3):203-11. doi: 10.1620/tjem.196.203.
• Background Spranger M, Schwab S, Wiebel M, Becker CM. [Adult Leigh syndrome. A rare differential diagnosis of central respiratory insufficiency]. Nervenarzt. 1995 Feb;66(2):144-9. German.
• Background Yasaki E, Saito Y, Nakano K, Katsumori H, Hayashi K, Nishikawa T, Osawa M. Characteristics of breathing abnormality in Leigh and its overlap syndromes. Neuropediatrics. 2001 Dec;32(6):299-306. doi: 10.1055/s-2001-20405.
• Background Sembrano E, Barthlen GM, Wallace S, Lamm C. Polysomnographic findings in a patient with the mitochondrial encephalomyopathy NARP. Neurology. 1997 Dec;49(6):1714-7. doi: 10.1212/wnl.49.6.1714.

Drugs

Indications