Coenzyme Q10 in Huntington's Disease (HD)

Summary

The goals of this trial are to determine if coenzyme Q10 is effective in slowing the worsening symptoms of Huntington's disease and to learn about the safety and acceptability of long-term coenzyme Q10 use by determining its effects on people with Huntington's disease.

Timeline

Start

2008-03

Primary completion

2014-11

Completion

2015-05

Publications

• Background Kowall N, Ferrante R, Martin J. Patterns of cell loss in Huntington's disease. Trends in Neurosciences 1987;10:24-29.
• Background Riley D, Lang A. Movement Disorders. In: Bradley W, Daroff R, Fenichel G, eds. Neurology in Clinical Practice. The Neurological Disorders. Boston: Butterworth-Heinemann, 1991: 1563-1601.
• Background Adams P, Falek A, Arnold J. Huntington disease in Georgia: age at onset. Am J Hum Genet. 1988 Nov;43(5):695-704.
• Background Conneally PM. Huntington disease: genetics and epidemiology. Am J Hum Genet. 1984 May;36(3):506-26.
• Background Harper PS. The epidemiology of Huntington's disease. Hum Genet. 1992 Jun;89(4):365-76. doi: 10.1007/BF00194305.
• Background Tanner CM, Goldman SM. Epidemiology of movement disorders. Curr Opin Neurol. 1994 Aug;7(4):340-5. doi: 10.1097/00019052-199408000-00011. No abstract available.
• Background Young AB, Shoulson I, Penney JB, Starosta-Rubinstein S, Gomez F, Travers H, Ramos-Arroyo MA, Snodgrass SR, Bonilla E, Moreno H, et al. Huntington's disease in Venezuela: neurologic features and functional decline. Neurology. 1986 Feb;36(2):244-9. doi: 10.1212/wnl.36.2.244.
• Background Bruyn G. Huntington's chorea: Historical clinical and laboratory synopsis. In: Vinken P, Bruyn G, eds. Handbook of Clinical Neurology. Amsterdam, 1968: 298-378.
• Background Leigh RJ, Newman SA, Folstein SE, Lasker AG, Jensen BA. Abnormal ocular motor control in Huntington's disease. Neurology. 1983 Oct;33(10):1268-75. doi: 10.1212/wnl.33.10.1268.
• Background Caine ED, Hunt RD, Weingartner H, Ebert MH. Huntington's dementia. Clinical and neuropsychological features. Arch Gen Psychiatry. 1978 Mar;35(3):377-84. doi: 10.1001/archpsyc.1978.01770270127013.
• Background Bamford KA, Caine ED, Kido DK, Plassche WM, Shoulson I. Clinical-pathologic correlation in Huntington's disease: a neuropsychological and computed tomography study. Neurology. 1989 Jun;39(6):796-801. doi: 10.1212/wnl.39.6.796.
• Background Sorensen SA, Fenger K. Causes of death in patients with Huntington's disease and in unaffected first degree relatives. J Med Genet. 1992 Dec;29(12):911-4. doi: 10.1136/jmg.29.12.911.
• Background Oliver JE. Huntington's chorea in Northamptonshire. Br J Psychiatry. 1970 Mar;116(532):241-53. doi: 10.1192/bjp.116.532.241. No abstract available.
• Background Greenamyre J, Shoulson I. Huntington's Disease. In: Calne D, ed. Neurodegenerative Diseases. Philadelphia: WB Saunders, 1994: 685-704.
• Background Shoulson I, Fahn S. Huntington disease: clinical care and evaluation. Neurology. 1979 Jan;29(1):1-3. doi: 10.1212/wnl.29.1.1. No abstract available.
• Background Feigin A, Kieburtz K, Bordwell K, Como P, Steinberg K, Sotack J, Zimmerman C, Hickey C, Orme C, Shoulson I. Functional decline in Huntington's disease. Mov Disord. 1995 Mar;10(2):211-4. doi: 10.1002/mds.870100213.
• Background Myers RH, Sax DS, Koroshetz WJ, Mastromauro C, Cupples LA, Kiely DK, Pettengill FK, Bird ED. Factors associated with slow progression in Huntington's disease. Arch Neurol. 1991 Aug;48(8):800-4. doi: 10.1001/archneur.1991.00530200036015.
• Background Penney JB Jr, Young AB, Shoulson I, Starosta-Rubenstein S, Snodgrass SR, Sanchez-Ramos J, Ramos-Arroyo M, Gomez F, Penchaszadeh G, Alvir J, et al. Huntington's disease in Venezuela: 7 years of follow-up on symptomatic and asymptomatic individuals. Mov Disord. 1990;5(2):93-9. doi: 10.1002/mds.870050202.
• Background Young AB, Penney JB, Starosta-Rubinstein S, Markel DS, Berent S, Giordani B, Ehrenkaufer R, Jewett D, Hichwa R. PET scan investigations of Huntington's disease: cerebral metabolic correlates of neurological features and functional decline. Ann Neurol. 1986 Sep;20(3):296-303. doi: 10.1002/ana.410200305.
• Background Kido D, Shoulson I, Manzione J, Harnish P. Measurement of caudate nucleus and putamen atrophy in patients with Huntington's disease. Neuroradiology 1991;33:604-606.
• Background Mazziotta JC. Huntington's disease: studies with structural imaging techniques and positron emission tomography. Semin Neurol. 1989 Dec;9(4):360-9. doi: 10.1055/s-2008-1041346. No abstract available.
• Background Beal MF, Ferrante RJ. Experimental therapeutics in transgenic mouse models of Huntington's disease. Nat Rev Neurosci. 2004 May;5(5):373-84. doi: 10.1038/nrn1386. No abstract available.
• Background A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group. Cell. 1993 Mar 26;72(6):971-83. doi: 10.1016/0092-8674(93)90585-e.
• Background Tabrizi SJ, Workman J, Hart PE, Mangiarini L, Mahal A, Bates G, Cooper JM, Schapira AH. Mitochondrial dysfunction and free radical damage in the Huntington R6/2 transgenic mouse. Ann Neurol. 2000 Jan;47(1):80-6. doi: 10.1002/1531-8249(200001)47:13.3.co;2-b.
• Background Cha JH. Transcriptional dysregulation in Huntington's disease. Trends Neurosci. 2000 Sep;23(9):387-92. doi: 10.1016/s0166-2236(00)01609-x.
• Background Ona VO, Li M, Vonsattel JP, Andrews LJ, Khan SQ, Chung WM, Frey AS, Menon AS, Li XJ, Stieg PE, Yuan J, Penney JB, Young AB, Cha JH, Friedlander RM. Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's disease. Nature. 1999 May 20;399(6733):263-7. doi: 10.1038/20446.
• Background Chen M, Ona VO, Li M, Ferrante RJ, Fink KB, Zhu S, Bian J, Guo L, Farrell LA, Hersch SM, Hobbs W, Vonsattel JP, Cha JH, Friedlander RM. Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat Med. 2000 Jul;6(7):797-801. doi: 10.1038/77528.
• Background Beal MF, Hyman BT, Koroshetz W. Do defects in mitochondrial energy metabolism underlie the pathology of neurodegenerative diseases? Trends Neurosci. 1993 Apr;16(4):125-31. doi: 10.1016/0166-2236(93)90117-5.
• Background Wellington CL, Ellerby LM, Hackam AS, Margolis RL, Trifiro MA, Singaraja R, McCutcheon K, Salvesen GS, Propp SS, Bromm M, Rowland KJ, Zhang T, Rasper D, Roy S, Thornberry N, Pinsky L, Kakizuka A, Ross CA, Nicholson DW, Bredesen DE, Hayden MR. Caspase cleavage of gene products associated with triplet expansion disorders generates truncated fragments containing the polyglutamine tract. J Biol Chem. 1998 Apr 10;273(15):9158-67. doi: 10.1074/jbc.273.15.9158.
• Background Brouillet E, Hantraye P, Ferrante RJ, Dolan R, Leroy-Willig A, Kowall NW, Beal MF. Chronic mitochondrial energy impairment produces selective striatal degeneration and abnormal choreiform movements in primates. Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):7105-9. doi: 10.1073/pnas.92.15.7105.
• Background Gu M, Gash MT, Mann VM, Javoy-Agid F, Cooper JM, Schapira AH. Mitochondrial defect in Huntington's disease caudate nucleus. Ann Neurol. 1996 Mar;39(3):385-9. doi: 10.1002/ana.410390317.
• Background Koroshetz WJ, Jenkins BG, Rosen BR, Beal MF. Energy metabolism defects in Huntington's disease and effects of coenzyme Q10. Ann Neurol. 1997 Feb;41(2):160-5. doi: 10.1002/ana.410410206.
• Background Sawa A, Wiegand GW, Cooper J, Margolis RL, Sharp AH, Lawler JF Jr, Greenamyre JT, Snyder SH, Ross CA. Increased apoptosis of Huntington disease lymphoblasts associated with repeat length-dependent mitochondrial depolarization. Nat Med. 1999 Oct;5(10):1194-8. doi: 10.1038/13518.
• Background Jenkins BG, Koroshetz WJ, Beal MF, Rosen BR. Evidence for impairment of energy metabolism in vivo in Huntington's disease using localized 1H NMR spectroscopy. Neurology. 1993 Dec;43(12):2689-95. doi: 10.1212/wnl.43.12.2689.
• Background Lodi R, Schapira AH, Manners D, Styles P, Wood NW, Taylor DJ, Warner TT. Abnormal in vivo skeletal muscle energy metabolism in Huntington's disease and dentatorubropallidoluysian atrophy. Ann Neurol. 2000 Jul;48(1):72-6.
• Background Panov AV, Gutekunst CA, Leavitt BR, Hayden MR, Burke JR, Strittmatter WJ, Greenamyre JT. Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines. Nat Neurosci. 2002 Aug;5(8):731-6. doi: 10.1038/nn884.
• Background Gines S, Seong IS, Fossale E, Ivanova E, Trettel F, Gusella JF, Wheeler VC, Persichetti F, MacDonald ME. Specific progressive cAMP reduction implicates energy deficit in presymptomatic Huntington's disease knock-in mice. Hum Mol Genet. 2003 Mar 1;12(5):497-508. doi: 10.1093/hmg/ddg046.
• Background Browne SE, Bowling AC, MacGarvey U, Baik MJ, Berger SC, Muqit MM, Bird ED, Beal MF. Oxidative damage and metabolic dysfunction in Huntington's disease: selective vulnerability of the basal ganglia. Ann Neurol. 1997 May;41(5):646-53. doi: 10.1002/ana.410410514.
• Background Ferrante RJ, Andreassen OA, Jenkins BG, Dedeoglu A, Kuemmerle S, Kubilus JK, Kaddurah-Daouk R, Hersch SM, Beal MF. Neuroprotective effects of creatine in a transgenic mouse model of Huntington's disease. J Neurosci. 2000 Jun 15;20(12):4389-97. doi: 10.1523/JNEUROSCI.20-12-04389.2000.
• Background Ferrante RJ, Andreassen OA, Dedeoglu A, Ferrante KL, Jenkins BG, Hersch SM, Beal MF. Therapeutic effects of coenzyme Q10 and remacemide in transgenic mouse models of Huntington's disease. J Neurosci. 2002 Mar 1;22(5):1592-9. doi: 10.1523/JNEUROSCI.22-05-01592.2002.
• Background Dedeoglu A, Kubilus JK, Yang L, Ferrante KL, Hersch SM, Beal MF, Ferrante RJ. Creatine therapy provides neuroprotection after onset of clinical symptoms in Huntington's disease transgenic mice. J Neurochem. 2003 Jun;85(6):1359-67. doi: 10.1046/j.1471-4159.2003.01706.x.
• Background Schilling G, Coonfield ML, Ross CA, Borchelt DR. Coenzyme Q10 and remacemide hydrochloride ameliorate motor deficits in a Huntington's disease transgenic mouse model. Neurosci Lett. 2001 Nov 27;315(3):149-53. doi: 10.1016/s0304-3940(01)02326-6.
• Background Matthews RT, Yang L, Browne S, Baik M, Beal MF. Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects. Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8892-7. doi: 10.1073/pnas.95.15.8892.
• Background Beal MF, Henshaw DR, Jenkins BG, Rosen BR, Schulz JB. Coenzyme Q10 and nicotinamide block striatal lesions produced by the mitochondrial toxin malonate. Ann Neurol. 1994 Dec;36(6):882-8. doi: 10.1002/ana.410360613.
• Background Pepping J. Coenzyme Q10. Am J Health Syst Pharm. 1999 Mar 15;56(6):519-21. doi: 10.1093/ajhp/56.6.519. No abstract available.
• 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 Ernster L, Dallner G. Biochemical, physiological and medical aspects of ubiquinone function. Biochim Biophys Acta. 1995 May 24;1271(1):195-204. doi: 10.1016/0925-4439(95)00028-3.
• Background Yamagami T, Okishio T, Toyama S, Kishi T. Correlation of serum coenzyme Q10 level and leukocute complex II activity in nformal and cardiovascular patients. In: Folkers K, Yamagami T, eds. Biomedical and clinical aspects of coenzyme Q: Elsevier Science Publishers, 1981: 79-89.
• Background Soderberg M, Edlund C, Kristensson K, Dallner G. Lipid compositions of different regions of the human brain during aging. J Neurochem. 1990 Feb;54(2):415-23. doi: 10.1111/j.1471-4159.1990.tb01889.x.
• Background Peyser CE, Folstein M, Chase GA, Starkstein S, Brandt J, Cockrell JR, Bylsma F, Coyle JT, McHugh PR, Folstein SE. Trial of d-alpha-tocopherol in Huntington's disease. Am J Psychiatry. 1995 Dec;152(12):1771-5. doi: 10.1176/ajp.152.12.1771.
• Background Ranen NG, Peyser CE, Coyle JT, Bylsma FW, Sherr M, Day L, Folstein MF, Brandt J, Ross CA, Folstein SE. A controlled trial of idebenone in Huntington's disease. Mov Disord. 1996 Sep;11(5):549-54. doi: 10.1002/mds.870110510.
• Background Kremer B, Clark CM, Almqvist EW, Raymond LA, Graf P, Jacova C, Mezei M, Hardy MA, Snow B, Martin W, Hayden MR. Influence of lamotrigine on progression of early Huntington disease: a randomized clinical trial. Neurology. 1999 Sep 22;53(5):1000-11. doi: 10.1212/wnl.53.5.1000.
• Background Puri BK, Leavitt BR, Hayden MR, Ross CA, Rosenblatt A, Greenamyre JT, Hersch S, Vaddadi KS, Sword A, Horrobin DF, Manku M, Murck H. Ethyl-EPA in Huntington disease: a double-blind, randomized, placebo-controlled trial. Neurology. 2005 Jul 26;65(2):286-92. doi: 10.1212/01.wnl.0000169025.09670.6d.
• Background Dubois B, Brand M, Garcia de Yebenes J, et al. European-Huntington's-disease-Initiative (EHDI)-Trial: Objectives, design, and description of the study population at the end of inclusion. Mov Dis 2002;17:S319.
• Background Bogentoft C, Edelund P, Olsson B, Widlund L, Westensen K. Biopharmaceutical aspects of intraveneous and oral administration of coenzyme Q10. In: Folkers K, Littarru G, Yamagami T, eds. Biomedical and clinical aspects of coenzyme Q.: Elsevier Science Publishers, 1991: 215-224.
• Background Lucker P, Wetselsberg N, Hennings G, Rehn D. Pharmacokinetics of coenzyme ubidecarenone in healthy volunteers. In: Folkers K, Littarru G, Yamagami T, eds. Biomedical and clinical aspects of coenzyme Q: Elsevier Science Publishers, 1984: 143-151.
• Background Mohr D, Bowry VW, Stocker R. Dietary supplementation with coenzyme Q10 results in increased levels of ubiquinol-10 within circulating lipoproteins and increased resistance of human low-density lipoprotein to the initiation of lipid peroxidation. Biochim Biophys Acta. 1992 Jun 26;1126(3):247-54. doi: 10.1016/0005-2760(92)90237-p.
• Background Micromedex. Ubidecarenone drug monograph. Engelwood 1995 May; Update 1998 Mar.
• Background Zhang Y, Aberg F, Appelkvist EL, Dallner G, Ernster L. Uptake of dietary coenzyme Q supplement is limited in rats. J Nutr. 1995 Mar;125(3):446-53. doi: 10.1093/jn/125.3.446.
• Background Weber C. Dietary intake and absorption of coenzyme Q. In: Kagan V, Quinn P, eds. Coenzyme Q: Molecular Mechanisms in Health and Disease. Boca Raton: CRC Press, 2001:209-215.
• Background Rundek T, Naini A, Sacco R, Coates K, DiMauro S. Atorvastatin decreases the coenzyme Q10 level in the blood of patients at risk for cardiovascular disease and stroke. Arch Neurol. 2004 Jun;61(6):889-92. doi: 10.1001/archneur.61.6.889.
• Background Saito Y, Kubo H, Bujo H, Yamamoto Y. The changes in plasma coenzyme Q10 level during the statin therapy for hypercholesterolemic patients. In: Second Conference of the International Coenzyme Q10 Association.; 2000, 2000: 59.
• Background De Pinieux G, Chariot P, Ammi-Said M, Louarn F, Lejonc JL, Astier A, Jacotot B, Gherardi R. Lipid-lowering drugs and mitochondrial function: effects of HMG-CoA reductase inhibitors on serum ubiquinone and blood lactate/pyruvate ratio. Br J Clin Pharmacol. 1996 Sep;42(3):333-7. doi: 10.1046/j.1365-2125.1996.04178.x.
• Background Watts GF, Castelluccio C, Rice-Evans C, Taub NA, Baum H, Quinn PJ. Plasma coenzyme Q (ubiquinone) concentrations in patients treated with simvastatin. J Clin Pathol. 1993 Nov;46(11):1055-7. doi: 10.1136/jcp.46.11.1055.
• Background Laaksonen R, Jokelainen K, Laakso J, Sahi T, Harkonen M, Tikkanen MJ, Himberg JJ. The effect of simvastatin treatment on natural antioxidants in low-density lipoproteins and high-energy phosphates and ubiquinone in skeletal muscle. Am J Cardiol. 1996 Apr 15;77(10):851-4. doi: 10.1016/S0002-9149(97)89180-1.
• Background Huntington Study Group. Minocycline safety and tolerability in Huntington disease. Neurology. 2004 Aug 10;63(3):547-9. doi: 10.1212/01.wnl.0000133403.30559.ff.
• Background Langsjoen H, Langsjoen P, Langsjoen P, Willis R, Folkers K. Usefulness of coenzyme Q10 in clinical cardiology: a long-term study. Mol Aspects Med. 1994;15 Suppl:s165-75. doi: 10.1016/0098-2997(94)90026-4.
• 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 Di Giovanni S, Mirabella M, Spinazzola A, Crociani P, Silvestri G, Broccolini A, Tonali P, Di Mauro S, Servidei S. Coenzyme Q10 reverses pathological phenotype and reduces apoptosis in familial CoQ10 deficiency. Neurology. 2001 Aug 14;57(3):515-8. doi: 10.1212/wnl.57.3.515.
• Background Lodi R, Hart PE, Rajagopalan B, Taylor DJ, Crilley JG, Bradley JL, Blamire AM, Manners D, Styles P, Schapira AH, Cooper JM. Antioxidant treatment improves in vivo cardiac and skeletal muscle bioenergetics in patients with Friedreich's ataxia. Ann Neurol. 2001 May;49(5):590-6.
• 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 Shults CW, Flint Beal M, Song D, Fontaine D. Pilot trial of high dosages of coenzyme Q10 in patients with Parkinson's disease. Exp Neurol. 2004 Aug;188(2):491-4. doi: 10.1016/j.expneurol.2004.05.003.
• Background Greenberg S, Frishman WH. Co-enzyme Q10: a new drug for cardiovascular disease. J Clin Pharmacol. 1990 Jul;30(7):596-608. doi: 10.1002/j.1552-4604.1990.tb01862.x.
• McGarry A, Auinger P, Kieburtz KD, Bredlau AL, Hersch SM, Rosas HD. Suicidality Risk Factors Across the CARE-HD, 2CARE, and CREST-E Clinical Trials in Huntington Disease. Neurol Clin Pract. 2022 Apr;12(2):131-138. doi: 10.1212/CPJ.0000000000001161.
• McGarry A, McDermott MP, Kieburtz K, Fung WLA, McCusker E, Peng J, de Blieck EA, Cudkowicz M; Huntington Study Group 2CARE Investigators and Coordinators. Risk factors for suicidality in Huntington disease: An analysis of the 2CARE clinical trial. Neurology. 2019 Apr 2;92(14):e1643-e1651. doi: 10.1212/WNL.0000000000007244. Epub 2019 Mar 8.
• McGarry A, McDermott M, Kieburtz K, de Blieck EA, Beal F, Marder K, Ross C, Shoulson I, Gilbert P, Mallonee WM, Guttman M, Wojcieszek J, Kumar R, LeDoux MS, Jenkins M, Rosas HD, Nance M, Biglan K, Como P, Dubinsky RM, Shannon KM, O'Suilleabhain P, Chou K, Walker F, Martin W, Wheelock VL, McCusker E, Jankovic J, Singer C, Sanchez-Ramos J, Scott B, Suchowersky O, Factor SA, Higgins DS Jr, Molho E, Revilla F, Caviness JN, Friedman JH, Perlmutter JS, Feigin A, Anderson K, Rodriguez R, McFarland NR, Margolis RL, Farbman ES, Raymond LA, Suski V, Kostyk S, Colcher A, Seeberger L, Epping E, Esmail S, Diaz N, Fung WL, Diamond A, Frank S, Hanna P, Hermanowicz N, Dure LS, Cudkowicz M; Huntington Study Group 2CARE Investigators and Coordinators. A randomized, double-blind, placebo-controlled trial of coenzyme Q10 in Huntington disease. Neurology. 2017 Jan 10;88(2):152-159. doi: 10.1212/WNL.0000000000003478. Epub 2016 Dec 2.

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Indications