Journal article
A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit
JAMA neurology, Vol.71(5), pp.543-552
05/2014
DOI: 10.1001/jamaneurol.2014.131
PMID: 24664227
Abstract
Importance Coenzyme Q10 (CoQ10), an antioxidant that supports mitochondrial function, has been shown in preclinical Parkinson disease (PD) models to reduce the loss of dopamine neurons, and was safe and well tolerated in early-phase human studies. A previous phase II study suggested possible clinical benefit. Objective To examine whether CoQ10 could slow disease progression in early PD. Design, Setting, and Participants A phase III randomized, placebo-controlled, double-blind clinical trial at 67 North American sites consisting of participants 30 years of age or older who received a diagnosis of PD within 5 years and who had the following inclusion criteria: the presence of a rest tremor, bradykinesia, and rigidity; a modified Hoehn and Yahr stage of 2.5 or less; and no anticipated need for dopaminergic therapy within 3 months. Exclusion criteria included the use of any PD medication within 60 days, the use of any symptomatic PD medication for more than 90 days, atypical or drug-induced parkinsonism, a Unified Parkinson’s Disease Rating Scale (UPDRS) rest tremor score of 3 or greater for any limb, a Mini-Mental State Examination score of 25 or less, a history of stroke, the use of certain supplements, and substantial recent exposure to CoQ10. Of 696 participants screened, 78 were found to be ineligible, and 18 declined participation. Interventions The remaining 600 participants were randomly assigned to receive placebo, 1200 mg/d of CoQ10, or 2400 mg/d of CoQ10; all participants received 1200 IU/d of vitamin E. Main Outcomes and Measures Participants were observed for 16 months or until a disability requiring dopaminergic treatment. The prospectively defined primary outcome measure was the change in total UPDRS score (Parts I-III) from baseline to final visit. The study was powered to detect a 3-point difference between an active treatment and placebo. Results The baseline characteristics of the participants were well balanced, the mean age was 62.5 years, 66% of participants were male, and the mean baseline total UPDRS score was 22.7. A total of 267 participants required treatment (94 received placebo, 87 received 1200 mg/d of CoQ10, and 86 received 2400 mg/d of CoQ10), and 65 participants (29 who received placebo, 19 who received 1200 mg/d of CoQ10, and 17 who received 2400 mg/d of CoQ10) withdrew prematurely. Treatments were well tolerated with no safety concerns. The study was terminated after a prespecified futility criterion was reached. At study termination, both active treatment groups showed slight adverse trends relative to placebo. Adjusted mean changes (worsening) in total UPDRS scores from baseline to final visit were 6.9 points (placebo), 7.5 points (1200 mg/d of CoQ10; P = .49 relative to placebo), and 8.0 points (2400 mg/d of CoQ10; P = .21 relative to placebo). Conclusions and Relevance Coenzyme Q10 was safe and well tolerated in this population, but showed no evidence of clinical benefit.
Details
- Title: Subtitle
- A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit
- Creators
- M Flint Beal - Department of Neurology, Weill Cornell Medical College, New York Hospital, New YorkDavid Oakes - Department of Biostatistics, University of Rochester Medical Center, Rochester, New YorkIra Shoulson - Department of Neurology, Georgetown University, Washington, DCClaire Henchcliffe - Department of Neurology, Weill Cornell Medical College, New York Hospital, New YorkWendy R Galpern - National Institutes of Health, Bethesda, MarylandRichard Haas - Department of Neurosciences, University of California, San Diego, La JollaJorge L Juncos - Department of Neurology, Emory University School of Medicine, Wesley Woods Center, Atlanta, GeorgiaJohn G Nutt - Department of Neurology, Oregon Health and Science University, PortlandTiffini Smith Voss - Merck, New JerseyBernard Ravina - Biogen Idec, Cambridge, MassachusettsClifford M Shults - Department of Neurosciences, University of California, San Diego, La Jolla10VA Medical Center, San Diego, CaliforniaKaren Helles - Department of Biostatistics, University of Rochester Medical Center, Rochester, New YorkVictoria Snively - Department of Biostatistics, University of Rochester Medical Center, Rochester, New YorkMark F Lew - Department of Neurology, Keck School of Medicine, University of Southern California, Los AngelesBrian Griebner - Department of Biostatistics, University of Rochester Medical Center, Rochester, New YorkArthur Watts - Department of Biostatistics, University of Rochester Medical Center, Rochester, New York12Department of Neurology, University of Rochester, Rochester, New YorkShan Gao - Department of Biostatistics, University of Rochester Medical Center, Rochester, New YorkEmmanuelle Pourcher - Québec Memory and Motor Skills Disorders Research Center, Clinique Sainte-Anne, Québec, CanadaLouisette Bond - Québec Memory and Motor Skills Disorders Research Center, Clinique Sainte-Anne, Québec, CanadaKatie Kompoliti - Rush University Medical Center, Chicago, IllinoisPinky Agarwal - Booth Gardner Parkinson's Care Center, EvergreenHealth, Kirkland, WashingtonCherissa Sia - Booth Gardner Parkinson's Care Center, EvergreenHealth, Kirkland, WashingtonMandar Jog - London Health Sciences Centre, London, Ontario, CanadaLinda Cole - London Health Sciences Centre, London, Ontario, CanadaMunira Sultana - London Health Sciences Centre, London, Ontario, CanadaRoger Kurlan - Overlook Medical Center, Atlantic Neuroscience Institute, Summit, New JerseyIrene Richard - Department of Neurology, University of Rochester, Rochester, New YorkCheryl Deeley - Department of Neurology, University of Rochester, Rochester, New YorkCheryl H Waters - Columbia University Medical Center, Neurological Institute, New York, New YorkAngel Figueroa - Columbia University Medical Center, Neurological Institute, New York, New YorkAni Arkun - Department of Neurology, Weill Cornell Medical College, New York Hospital, New YorkWilliam G Ondo - Department of Neurology, University of Texas Health Science Center at HoustonMatthew Brodsky - Department of Neurology, Oregon Health and Science University, PortlandChristine B Hunter - Department of Neurology, Baylor College of Medicine, Houston, TexasJoohi Jimenez-Shahed - Department of Neurology, Baylor College of Medicine, Houston, TexasAlicia Palao - Department of Neurology, Baylor College of Medicine, Houston, TexasJanis M Miyasaki - Morton and Gloria Shulman Movement Disorders Centre, Toronto Western Hospital, University of Toronto, Toronto, Ontario, CanadaJulie So - Morton and Gloria Shulman Movement Disorders Centre, Toronto Western Hospital, University of Toronto, Toronto, Ontario, CanadaJames Tetrud - The Parkinson's Institute and Clinical Center, Sunnyvale, CaliforniaLiza Reys - The Parkinson's Institute and Clinical Center, Sunnyvale, CaliforniaKatharine Smith - The Parkinson's Institute and Clinical Center, Sunnyvale, CaliforniaCarlos Singer - Department of Neurology, University of Miami School of Medicine, Miami, FloridaAnita Blenke - Department of Neurology, University of Miami School of Medicine, Miami, FloridaDavid S Russell - Institute for Neurodegenerative Disorders, New Haven, ConnecticutCandace Cotto - Institute for Neurodegenerative Disorders, New Haven, ConnecticutJoseph H Friedman - Department of Neurology, Butler Hospital, Providence, Rhode Island26Alpert Medical School, Brown University, Providence, Rhode IslandMargaret Lannon - Department of Neurology, Butler Hospital, Providence, Rhode Island27Port City Neurology, Inc, Scarborough, MaineLin Zhang - Department of Neurology, University of California, Davis, School of Medicine and Sacramento VA Medical Center, SacramentoEdward Drasby - Port City Neurology, Inc, Scarborough, MaineRajeev Kumar - Colorado Neurological Institute, EnglewoodThyagarajan Subramanian - Milton S. Hershey Medical Center, Department of Neurology, Pennsylvania State Hershey College of Medicine, HersheyDonna Stuppy Ford - Milton S. Hershey Medical Center, Department of Neurology, Pennsylvania State Hershey College of Medicine, HersheyDavid A Grimes - Ottawa Hospital Civic Site, Ottawa, Ontario, CanadaDiane Cote - Ottawa Hospital Civic Site, Ottawa, Ontario, CanadaJennifer Conway - Ottawa Hospital Civic Site, Ottawa, Ontario, CanadaAndrew D Siderowf - Avid Radiopharmaceuticals, Philadelphia, PennsylvaniaMarian Leslie Evatt - Department of Neurology, Emory University School of Medicine, Wesley Woods Center, Atlanta, Georgia33Atlanta VA Medical Center, Atlanta, GeorgiaBarbara Sommerfeld - Department of Neurology, Emory University School of Medicine, Wesley Woods Center, Atlanta, GeorgiaAbraham N Lieberman - Muhammad Ali Parkinson Center, Barrow Neurological Institute, St Joseph's Hospital and Medical Center, Phoenix, ArizonaMichael S Okun - Department of Neurology, University of Florida Center for Movement Disorders and Neurorestoration, GainesvilleRamon L Rodriguez - Department of Neurology, University of Florida Center for Movement Disorders and Neurorestoration, GainesvilleStacy Merritt - Department of Neurology, University of Florida Center for Movement Disorders and Neurorestoration, GainesvilleCamille Louise Swartz - Department of Neurology, University of Florida Center for Movement Disorders and Neurorestoration, GainesvilleW R Wayne Martin - Glenrose Rehabilitation Hospital, University of Alberta, Edmonton, Alberta, CanadaPamela King - Glenrose Rehabilitation Hospital, University of Alberta, Edmonton, Alberta, CanadaNatividad Stover - Department of Neurology, University of Alabama at BirminghamStephanie Guthrie - Department of Neurology, University of Alabama at BirminghamRay L Watts - Department of Neurology, University of Alabama at BirminghamAnwar Ahmed - Center for Neurological Restoration, Department of Neurology, Cleveland Clinic, Cleveland, OhioHubert H Fernandez - Center for Neurological Restoration, Department of Neurology, Cleveland Clinic, Cleveland, OhioAdrienna Winters - Center for Neurological Restoration, Department of Neurology, Cleveland Clinic, Cleveland, OhioZoltan Mari - Department of Neurology, Johns Hopkins University, Baltimore, MarylandTed M Dawson - Department of Neurology, Johns Hopkins University, Baltimore, MarylandBecky Dunlop - Department of Neurology, Johns Hopkins University, Baltimore, MarylandAndrew S Feigin - Feinstein Institute for Medical Research, Center for Neurosciences, Manhasset, New YorkBarbara Shannon - Feinstein Institute for Medical Research, Center for Neurosciences, Manhasset, New YorkMelissa Jill Nirenberg - Department of Neurology, New York University Langone Medical Center, New YorkMattson Ogg - Department of Neurology, Weill Cornell Medical College, New York Hospital, New YorkSamuel A Ellias - Department of Neurology, Boston University School of Medicine, Boston, MassachusettsCathi-Ann Thomas - Department of Neurology, Boston University School of Medicine, Boston, MassachusettsKaren Frei - The Parkinson's and Movement Disorder Institute, Fountain Valley, CaliforniaIvan Bodis-Wollner - State University of New York, Downstate Medical Center, Brooklyn, New YorkSofya Glazman - State University of New York, Downstate Medical Center, Brooklyn, New YorkThomas Mayer - State University of New York, Downstate Medical Center, Brooklyn, New YorkRobert A Hauser - Department of Neurology, University of South Florida, TampaRajesh Pahwa - Department of Neurology, University of Kansas Medical Center, Kansas CityApril Langhammer - Department of Neurology, University of Kansas Medical Center, Kansas CityRanjit Ranawaya - Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, CanadaLorelei Derwent - Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, CanadaKapil D Sethi - Department of Neurology, Georgia Health Science University, AugustaBuff Farrow - Department of Neurology, Georgia Health Science University, AugustaRajan Prakash - Department of Neurology, Georgia Health Science University, AugustaIrene Litvan - Department of Neurosciences, University of California, San Diego, La JollaAnnette Robinson - Department of Neurology, University of Louisville, KentuckyAlok Sahay - University of Cincinnati College of Medicine, Cincinnati, OhioMaureen Gartner - University of Cincinnati College of Medicine, Cincinnati, OhioVanessa K Hinson - Department of Neurology, Medical University of South Carolina, CharlestonSamuel Markind - Associated Neurologists, PC, Danbury, ConnecticutMelisa Pelikan - Associated Neurologists, PC, Danbury, ConnecticutJoel S Perlmutter - Department of Neurology, Washington University in St Louis, MissouriJohanna Hartlein - Department of Neurology, Washington University in St Louis, MissouriEric Molho - Movement Disorders Center, Albany Medical Center, Albany, New YorkSharon Evans - Movement Disorders Center, Albany Medical Center, Albany, New YorkCharles H Adler - Parkinson's Disease and Movement Disorders Center, Department of Neurology, Mayo Clinic, Scottsdale, ArizonaAmy Duffy - Parkinson's Disease and Movement Disorders Center, Department of Neurology, Mayo Clinic, Scottsdale, ArizonaMarlene Lind - Parkinson's Disease and Movement Disorders Center, Department of Neurology, Mayo Clinic, Scottsdale, ArizonaLawrence Elmer - Center for Neurological Health, University of Toledo, Toledo, OhioKathy Davis - Department of Neurology, Medical University of Ohio at ToledoJulia Spears - Department of Neurology, Medical University of Ohio at ToledoStephanie Wilson - Department of Neurology, Medical University of Ohio at ToledoMaureen A Leehey - Department of Neurology, University of Colorado Health Science Center, DenverNeal Hermanowicz - Department of Neurology, University of California, Irvine Medical Center, IrvineShari Niswonger - Department of Neurology, University of California, Irvine Medical Center, IrvineHolly A Shill - Banner Sun Health Research Institute, Sun City, ArizonaSanja Obradov - Banner Sun Health Research Institute, Sun City, ArizonaAlex Rajput - Department of Neurology, University of Saskatchewan, Royal University Hospital, Saskatchewan, CanadaMarilyn Cowper - Department of Neurology, University of Saskatchewan, Royal University Hospital, Saskatchewan, CanadaStephanie Lessig - Department of Neurology, University of California, San Diego, La JollaDavid Song - Department of Neurology, University of California, San Diego, La JollaDeborah Fontaine - Department of Neurology, University of California, San Diego, La JollaCindy Zadikoff - Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IllinoisKaren Williams - Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IllinoisKaren A Blindauer - Department of Neurology, Medical College of Wisconsin, MilwaukeeJo Bergholte - Department of Neurology, Medical College of Wisconsin, MilwaukeeClara Schindler Propsom - Department of Neurology, Medical College of Wisconsin, MilwaukeeMark A Stacy - Department of Neurology, Duke University, Durham, North CarolinaJoanne Field - Department of Neurology, Duke University, Durham, North CarolinaDragos Mihaila - State University of New York Upstate Medical Center and Syracuse VA Medical Center, SyracuseMark Chilton - State University of New York Upstate Medical Center and Syracuse VA Medical Center, SyracuseErgun Y Uc - Department of Neurology, University of Iowa, Iowa CityJeri Sieren - Department of Neurology, University of Iowa, Iowa CityDavid K Simon - Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MassachusettsLauren Kraics - Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MassachusettsAlthea Silver - Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MassachusettsJames T Boyd - Department of Neurology, University of Vermont College of Medicine, BurlingtonRobert W Hamill - Department of Neurology, University of Vermont College of Medicine, BurlingtonChristopher Ingvoldstad - Department of Neurology, University of Vermont College of Medicine, BurlingtonJennifer Young - Department of Neurology, University of Vermont College of Medicine, BurlingtonSandra K Kostyk - Department of Neurology, Ohio State University, ColumbusKaren Thomas - Department of Neurology, Ohio State University, ColumbusJoanne Wojcieszek - Department of Neurology, Indiana University School of Medicine, IndianapolisRonald F Pfeiffer - Department of Neurology, University of Tennessee Health Science Center, MemphisMichel Panisset - Department of Neurology, CHUM-Hôpital Notre-Dame, Montréal, Québec, CanadaMonica Beland - Department of Neurology, CHUM-Hôpital Notre-Dame, Montréal, Québec, CanadaStephen G Reich - Department of Neurology, University of Maryland School of Science, BaltimoreMichelle Cines - Department of Neurology, University of Maryland School of Science, BaltimoreNancy Zappala - Department of Neurology, University of Maryland School of Science, BaltimoreJean Rivest - Department of Neurology, University of Sherbrooke, Québec, CanadaRichard Zweig - Department of Neurology, Louisiana State University Health Science Center, ShreveportL Pepper Lumina - Department of Neurology, Louisiana State University Health Science Center, ShreveportColette Lynn Hilliard - Lewis Hall Singletary Oncology Center, Thomasville, GeorgiaStephen Grill - Department of Neurology, Johns Hopkins University, Baltimore, MarylandMarye Kellermann - Parkinson and Movement Disorders Center of Maryland, ElkridgePaul Tuite - Department of Neurology, University of Minnesota, MinneapolisSusan Rolandelli - Department of Neurology, University of Minnesota, MinneapolisUn Jung Kang - Department of Neurology, University of Chicago, Chicago, IllinoisJoan Young - Department of Neurology, University of Chicago, Chicago, IllinoisJayaraman Rao - Department of Neurology, Ochsner Clinic Foundation, New Orleans, LouisianaMaureen M Cook - Department of Neurology, Ochsner Clinic Foundation, New Orleans, LouisianaLawrence Severt - Department of Neurology, Beth Israel Medical Center, New York, New YorkKaryn Boyar - Department of Neurology, Beth Israel Medical Center, New York, New York
- Resource Type
- Journal article
- Publication Details
- JAMA neurology, Vol.71(5), pp.543-552
- DOI
- 10.1001/jamaneurol.2014.131
- PMID
- 24664227
- NLM abbreviation
- JAMA Neurol
- ISSN
- 2168-6149
- eISSN
- 2168-6157
- Publisher
- United States
- Grant note
- U01 NS050573 / NINDS NIH HHS R01 AG024040 / NIA NIH HHS U01 NS 050324 / NINDS NIH HHS
- Language
- English
- Date published
- 05/2014
- Academic Unit
- Neurology
- Record Identifier
- 9984014018602771
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