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JAMA Neurol. 2014 May;71(5):543-52. doi: 10.1001/jamaneurol.2014.131.

A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit.

Parkinson Study Group QE3 Investigators, Beal MF1, Oakes D2, Shoulson I3, Henchcliffe C1, Galpern WR4, Haas R5, Juncos JL6, Nutt JG7, Voss TS8, Ravina B9, Shults CM10, Helles K2, Snively V2, Lew MF11, Griebner B2, Watts A12, Gao S2, Pourcher E13, Bond L13, Kompoliti K14, Agarwal P15, Sia C15, Jog M16, Cole L16, Sultana M16, Kurlan R17, Richard I18, Deeley C18, Waters CH19, Figueroa A19, Arkun A1, Brodsky M7, Ondo WG20, Hunter CB21, Jimenez-Shahed J21, Palao A21, Miyasaki JM22, So J22, Tetrud J23, Reys L23, Smith K23, Singer C24, Blenke A24, Russell DS25, Cotto C25, Friedman JH26, Lannon M27, Zhang L28, Drasby E29, Kumar R30, Subramanian T31, Ford DS31, Grimes DA32, Cote D32, Conway J32, Siderowf AD33, Evatt ML34, Sommerfeld B6, Lieberman AN35, Okun MS36, Rodriguez RL36, Merritt S36, Swartz CL36, Martin WR37, King P37, Stover N38, Guthrie S38, Watts RL38, Ahmed A39, Fernandez HH39, Winters A39, Mari Z40, Dawson TM40, Dunlop B40, Feigin AS41, Shannon B41, Nirenberg MJ42, Ogg M1, Ellias SA43, Thomas CA43, Frei K44, Bodis-Wollner I45, Glazman S45, Mayer T45, Hauser RA46, Pahwa R47, Langhammer A47, Ranawaya R48, Derwent L48, Sethi KD49, Farrow B49, Prakash R49, Litvan I5, Robinson A50, Sahay A51, Gartner M51, Hinson VK52, Markind S53, Pelikan M53, Perlmutter JS54, Hartlein J54, Molho E55, Evans S55, Adler CH56, Duffy A56, Lind M56, Elmer L57, Davis K58, Spears J58, Wilson S58, Leehey MA59, Hermanowicz N60, Niswonger S60, Shill HA61, Obradov S61, Rajput A62, Cowper M62, Lessig S63, Song D63, Fontaine D63, Zadikoff C64, Williams K64, Blindauer KA65, Bergholte J65, Propsom CS65, Stacy MA66, Field J66, Mihaila D67, Chilton M67, Uc EY68, Sieren J68, Simon DK69, Kraics L69, Silver A69, Boyd JT70, Hamill RW70, Ingvoldstad C70, Young J70, Thomas K71, Kostyk SK71, Wojcieszek J72, Pfeiffer RF73, Panisset M74, Beland M74, Reich SG75, Cines M75, Zappala N75, Rivest J76, Zweig R77, Lumina LP77, Hilliard CL78, Grill S40, Kellermann M79, Tuite P80, Rolandelli S80, Kang UJ81, Young J81, Rao J82, Cook MM82, Severt L83, Boyar K83.

Collaborators (208)

Oakes D, Beal M, Shoulson I, Galpern WR, Haas R, Henchcliffe C, Juncos JL, Nutt J, Ravina B, Voss T, Shults C, Pourcher E, Bond L, Kompoliti K, Agarwal P, Sia C, Jog M, Cole L, Sultana M, Kurlan R, Richard I, Deeley C, Waters C, Figueroa A, Arkun A, Brodsky M, Ondo W, Hunter C, Jimenez-Shahed J, Palao A, Miyasaki J, So J, Tetrud J, Reys L, Smith K, Singer C, Blenke A, Russell D, Cotto C, Friedman J, Lannon M, Zhang L, Drasby E, Lannon M, Kumar R, Subramanian T, Ford DS, Grimes D, Cote D, Conway J, Siderowf A, Evatt M, Sommerfeld B, Lieberman A, Okun MS, Rodriguez R, Merritt S, Swartz C, Martin W, King P, Stover N, Guthrie S, Watts R, Ahmed A, Fernandez H, Winters A, Mari Z, Dawson T, Dunlop B, Feigin A, Shannon B, Nirenberg MJ, Ogg M, Ellias S, Thomas CA, Frei K, Bodis-Wollner I, Glazman S, Mayer T, Hauser RA, Pahwa R, Langhammer A, Ranawaya R, Derwent L, Sethi K, Farrow B, Prakash R, Litvan I, Robinson A, Sahay A, Gartner M, Hinson V, Markind S, Pelikan M, Perlmutter JS, Hartlein J, Molho E, Evans S, Adler C, Duffy A, Lind M, Elmer L, Davis K, Spears J, Wilson S, Leehey M, Hermanowicz N, Niswonger S, Shill H, Obradov S, Rajput A, Cowper M, Lessig S, Song D, Fontaine D, Zadikoff C, Williams K, Blindauer K, Bergholte J, Propsom CS, Stacy M, Field J, Mihaila D, Chilton M, Uc E, Sieren J, Simon DK, Kraics L, Silver A, Boyd J, Hamill R, Ingvoldstad C, Young J, Thomas K, Kostyk S, Wojcieszek J, Pfeiffer RF, Panisset M, Beland M, Reich S, Cines M, Zappala N, Rivest J, Zweig R, Lumina L, Hilliard C, Grill S, Kellermann M, Tuite P, Rolandelli S, Kang UJ, Young J, Rao J, Cook M, Severt W, Boyar K, Oakes D, McDermott M, Watts A, Gao S, Griebner B, Helles K, Plumb S, Snively V, Lew M, Voss T, Gross C, Albin R, Bell KL, Chen DT, Levy DE, Beimler A, Doolan R, Henderson S, Lang L, Lau G, McMullen N, Rothenburgh K, McCoy A, Dorward BJ, Tran M, Sombai J, Quesada M, Hupcey R, Miracle D, Altin L, Weeks ML, Simpson E, Suelter M, Scott I, McMurray R, Velcheva M, McClain T, Khavarian L, Zimmerman J, Zomok M, Scott ME, Olalde H, Miller J, Oesterle C, Pancake P, Belden J, Soucy D, Johnson L, Kashouty R, Roth L, Niles L, Nickels B.

Author information

1
Department of Neurology, Weill Cornell Medical College, New York Hospital, New York.
2
Department of Biostatistics, University of Rochester Medical Center, Rochester, New York.
3
Department of Neurology, Georgetown University, Washington, DC.
4
National Institutes of Health, Bethesda, Maryland.
5
Department of Neurosciences, University of California, San Diego, La Jolla.
6
Department of Neurology, Emory University School of Medicine, Wesley Woods Center, Atlanta, Georgia.
7
Department of Neurology, Oregon Health and Science University, Portland.
8
Merck, New Jersey.
9
Biogen Idec, Cambridge, Massachusetts.
10
Department of Neurosciences, University of California, San Diego, La Jolla10VA Medical Center, San Diego, California.
11
Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles.
12
Department of Biostatistics, University of Rochester Medical Center, Rochester, New York12Department of Neurology, University of Rochester, Rochester, New York.
13
Québec Memory and Motor Skills Disorders Research Center, Clinique Sainte-Anne, Québec, Canada.
14
Rush University Medical Center, Chicago, Illinois.
15
Booth Gardner Parkinson's Care Center, EvergreenHealth, Kirkland, Washington.
16
London Health Sciences Centre, London, Ontario, Canada.
17
Overlook Medical Center, Atlantic Neuroscience Institute, Summit, New Jersey.
18
Department of Neurology, University of Rochester, Rochester, New York.
19
Columbia University Medical Center, Neurological Institute, New York, New York.
20
Department of Neurology, University of Texas Health Science Center at Houston.
21
Department of Neurology, Baylor College of Medicine, Houston, Texas.
22
Morton and Gloria Shulman Movement Disorders Centre, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada.
23
The Parkinson's Institute and Clinical Center, Sunnyvale, California.
24
Department of Neurology, University of Miami School of Medicine, Miami, Florida.
25
Institute for Neurodegenerative Disorders, New Haven, Connecticut.
26
Department of Neurology, Butler Hospital, Providence, Rhode Island26Alpert Medical School, Brown University, Providence, Rhode Island.
27
Department of Neurology, Butler Hospital, Providence, Rhode Island27Port City Neurology, Inc, Scarborough, Maine.
28
Department of Neurology, University of California, Davis, School of Medicine and Sacramento VA Medical Center, Sacramento.
29
Port City Neurology, Inc, Scarborough, Maine.
30
Colorado Neurological Institute, Englewood.
31
Milton S. Hershey Medical Center, Department of Neurology, Pennsylvania State Hershey College of Medicine, Hershey.
32
Ottawa Hospital Civic Site, Ottawa, Ontario, Canada.
33
Avid Radiopharmaceuticals, Philadelphia, Pennsylvania.
34
Department of Neurology, Emory University School of Medicine, Wesley Woods Center, Atlanta, Georgia33Atlanta VA Medical Center, Atlanta, Georgia.
35
Muhammad Ali Parkinson Center, Barrow Neurological Institute, St Joseph's Hospital and Medical Center, Phoenix, Arizona.
36
Department of Neurology, University of Florida Center for Movement Disorders and Neurorestoration, Gainesville.
37
Glenrose Rehabilitation Hospital, University of Alberta, Edmonton, Alberta, Canada.
38
Department of Neurology, University of Alabama at Birmingham.
39
Center for Neurological Restoration, Department of Neurology, Cleveland Clinic, Cleveland, Ohio.
40
Department of Neurology, Johns Hopkins University, Baltimore, Maryland.
41
Feinstein Institute for Medical Research, Center for Neurosciences, Manhasset, New York.
42
Department of Neurology, New York University Langone Medical Center, New York.
43
Department of Neurology, Boston University School of Medicine, Boston, Massachusetts.
44
The Parkinson's and Movement Disorder Institute, Fountain Valley, California.
45
State University of New York, Downstate Medical Center, Brooklyn, New York.
46
Department of Neurology, University of South Florida, Tampa.
47
Department of Neurology, University of Kansas Medical Center, Kansas City.
48
Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.
49
Department of Neurology, Georgia Health Science University, Augusta.
50
Department of Neurology, University of Louisville, Kentucky.
51
University of Cincinnati College of Medicine, Cincinnati, Ohio.
52
Department of Neurology, Medical University of South Carolina, Charleston.
53
Associated Neurologists, PC, Danbury, Connecticut.
54
Department of Neurology, Washington University in St Louis, Missouri.
55
Movement Disorders Center, Albany Medical Center, Albany, New York.
56
Parkinson's Disease and Movement Disorders Center, Department of Neurology, Mayo Clinic, Scottsdale, Arizona.
57
Center for Neurological Health, University of Toledo, Toledo, Ohio.
58
Department of Neurology, Medical University of Ohio at Toledo.
59
Department of Neurology, University of Colorado Health Science Center, Denver.
60
Department of Neurology, University of California, Irvine Medical Center, Irvine.
61
Banner Sun Health Research Institute, Sun City, Arizona.
62
Department of Neurology, University of Saskatchewan, Royal University Hospital, Saskatchewan, Canada.
63
Department of Neurology, University of California, San Diego, La Jolla.
64
Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
65
Department of Neurology, Medical College of Wisconsin, Milwaukee.
66
Department of Neurology, Duke University, Durham, North Carolina.
67
State University of New York Upstate Medical Center and Syracuse VA Medical Center, Syracuse.
68
Department of Neurology, University of Iowa, Iowa City.
69
Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
70
Department of Neurology, University of Vermont College of Medicine, Burlington.
71
Department of Neurology, Ohio State University, Columbus.
72
Department of Neurology, Indiana University School of Medicine, Indianapolis.
73
Department of Neurology, University of Tennessee Health Science Center, Memphis.
74
Department of Neurology, CHUM-Hôpital Notre-Dame, Montréal, Québec, Canada.
75
Department of Neurology, University of Maryland School of Science, Baltimore.
76
Department of Neurology, University of Sherbrooke, Québec, Canada.
77
Department of Neurology, Louisiana State University Health Science Center, Shreveport.
78
Lewis Hall Singletary Oncology Center, Thomasville, Georgia.
79
Parkinson and Movement Disorders Center of Maryland, Elkridge.
80
Department of Neurology, University of Minnesota, Minneapolis.
81
Department of Neurology, University of Chicago, Chicago, Illinois.
82
Department of Neurology, Ochsner Clinic Foundation, New Orleans, Louisiana.
83
Department of Neurology, Beth Israel Medical Center, New York, New York.

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.

TRIAL REGISTRATION:

clinicaltrials.gov Identifier: NCT00740714.

PMID:
24664227
DOI:
10.1001/jamaneurol.2014.131
[Indexed for MEDLINE]
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