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

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.

• Authors: Parkinson Study Group QE3 Investigators, M Flint Beal, David Oakes, Ira Shoulson, Claire Henchcliffe, Wendy R Galpern, Richard Haas, Jorge L Juncos, John G Nutt, Tiffini Smith Voss, Bernard Ravina, Clifford M Shults, Karen Helles, Victoria Snively, Mark F Lew, Brian Griebner, Arthur Watts, Shan Gao, Emmanuelle Pourcher, Louisette Bond, Katie Kompoliti, Pinky Agarwal, Cherissa Sia, Mandar Jog, Linda Cole, Munira Sultana, Roger Kurlan, Irene Richard, Cheryl Deeley, Cheryl H Waters, Angel Figueroa, Ani Arkun, Matthew Brodsky, William G Ondo, Christine B Hunter, Joohi Jimenez-Shahed, Alicia Palao, Janis M Miyasaki, Julie So, James Tetrud, Liza Reys, Katharine Smith, Carlos Singer, Anita Blenke, David S Russell, Candace Cotto, Joseph H Friedman, Margaret Lannon, Lin Zhang, Edward Drasby, Rajeev Kumar, Thyagarajan Subramanian, Donna Stuppy Ford, David A Grimes, Diane Cote, Jennifer Conway, Andrew D Siderowf, Marian Leslie Evatt, Barbara Sommerfeld, Abraham N Lieberman, Michael S Okun, Ramon L Rodriguez, Stacy Merritt, Camille Louise Swartz, W R Wayne Martin, Pamela King, Natividad Stover, Stephanie Guthrie, Ray L Watts, Anwar Ahmed, Hubert H Fernandez, Adrienna Winters, Zoltan Mari, Ted M Dawson, Becky Dunlop, Andrew S Feigin, Barbara Shannon, Melissa Jill Nirenberg, Mattson Ogg, Samuel A Ellias, Cathi-Ann Thomas, Karen Frei, Ivan Bodis-Wollner, Sofya Glazman, Thomas Mayer, Robert A Hauser, Rajesh Pahwa, April Langhammer, Ranjit Ranawaya, Lorelei Derwent, Kapil D Sethi, Buff Farrow, Rajan Prakash, Irene Litvan, Annette Robinson, Alok Sahay, Maureen Gartner, Vanessa K Hinson, Samuel Markind, Melisa Pelikan, Joel S Perlmutter, Johanna Hartlein, Eric Molho, Sharon Evans, Charles H Adler, Amy Duffy, Marlene Lind, Lawrence Elmer, Kathy Davis, Julia Spears, Stephanie Wilson, Maureen A Leehey, Neal Hermanowicz, Shari Niswonger, Holly A Shill, Sanja Obradov, Alex Rajput, Marilyn Cowper, Stephanie Lessig, David Song, Deborah Fontaine, Cindy Zadikoff, Karen Williams, Karen A Blindauer, Jo Bergholte, Clara Schindler Propsom, Mark A Stacy, Joanne Field, Dragos Mihaila, Mark Chilton, Ergun Y Uc, Jeri Sieren, David K Simon, Lauren Kraics, Althea Silver, James T Boyd, Robert W Hamill, Christopher Ingvoldstad, Jennifer Young, Karen Thomas, Sandra K Kostyk, Joanne Wojcieszek, Ronald F Pfeiffer, Michel Panisset, Monica Beland, Stephen G Reich, Michelle Cines, Nancy Zappala, Jean Rivest, Richard Zweig, L Pepper Lumina, Colette Lynn Hilliard, Stephen Grill, Marye Kellermann, Paul Tuite, Susan Rolandelli, Un Jung Kang, Joan Young, Jayaraman Rao, Maureen M Cook, Lawrence Severt, Karyn Boyar
• Journal: JAMA neurology (JAMA Neurol) Vol. 71 Issue 5 Pg. 543-52 (May 2014) ISSN: 2168-6157 [Electronic] United States
• PMID: 24664227 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Ubiquinone
• coenzyme Q10

Topics

• Aged
• Antioxidants (administration & dosage, metabolism)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Early Diagnosis
• Female
• Humans
• Male
• Middle Aged
• Parkinson Disease (diagnosis, drug therapy, enzymology)
• Prospective Studies
• Treatment Outcome
• Ubiquinone (administration & dosage, analogs & derivatives, blood)