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

The Parkinson Study Group QE3 Investigators

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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.

Original languageEnglish (US)
Pages (from-to)543-552
Number of pages10
JournalJAMA Neurology
Volume75
Issue number1
DOIs
StatePublished - 2014

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coenzyme Q10
Parkinson Disease
Randomized Controlled Trials
Placebos
Tremor
Therapeutics
Secondary Parkinson Disease

ASJC Scopus subject areas

  • Clinical Neurology

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A randomized clinical trial of high-dosage coenzyme Q10 in early parkinson disease no evidence of benefit. / The Parkinson Study Group QE3 Investigators.

In: JAMA Neurology, Vol. 75, No. 1, 2014, p. 543-552.

Research output: Contribution to journalArticle

The Parkinson Study Group QE3 Investigators. / A randomized clinical trial of high-dosage coenzyme Q10 in early parkinson disease no evidence of benefit. In: JAMA Neurology. 2014 ; Vol. 75, No. 1. pp. 543-552.
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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.",
author = "{The Parkinson Study Group QE3 Investigators} and {Flint Beal}, M. and David Oakes and Ira Shoulson and Claire Henchcliffe and Galpern, {Wendy R.} and Richard Haas and Juncos, {Jorge L.} and Nutt, {John G.} and Voss, {Tiffini Smith} and Bernard Ravina and Shults, {Clifford M.} and Karen Helles and Victoria Snively and Lew, {Mark F.} and Brian Griebner and Arthur Watts and Shan Gao and Emmanuelle Pourcher and Louisette Bond and Katie Kompoliti and Pinky Agarwal and Cherissa Sia and Mandar Jog and Linda Cole and Munira Sultana and Roger Kurlan and Irene Richard and Cheryl Deeley and Waters, {Cheryl H.} and Angel Figueroa and Ani Arkun and Matthew Brodsky and Ondo, {William G.} and Hunter, {Christine B.} and Joohi Jimenez-Shahed and Alicia Palao and Miyasaki, {Janis M.} and Julie So and James Tetrud and Liza Reys and Katharine Smith and Carlos Singer and Anita Blenke and Russell, {David S.} and Candace Cotto and Friedman, {Joseph H.} and Margaret Lannon and Lin Zhang and Edward Drasby and Joanne Wojcieszek",
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T1 - A randomized clinical trial of high-dosage coenzyme Q10 in early parkinson disease no evidence of benefit

AU - The Parkinson Study Group QE3 Investigators

AU - Flint Beal, M.

AU - Oakes, David

AU - Shoulson, Ira

AU - Henchcliffe, Claire

AU - Galpern, Wendy R.

AU - Haas, Richard

AU - Juncos, Jorge L.

AU - Nutt, John G.

AU - Voss, Tiffini Smith

AU - Ravina, Bernard

AU - Shults, Clifford M.

AU - Helles, Karen

AU - Snively, Victoria

AU - Lew, Mark F.

AU - Griebner, Brian

AU - Watts, Arthur

AU - Gao, Shan

AU - Pourcher, Emmanuelle

AU - Bond, Louisette

AU - Kompoliti, Katie

AU - Agarwal, Pinky

AU - Sia, Cherissa

AU - Jog, Mandar

AU - Cole, Linda

AU - Sultana, Munira

AU - Kurlan, Roger

AU - Richard, Irene

AU - Deeley, Cheryl

AU - Waters, Cheryl H.

AU - Figueroa, Angel

AU - Arkun, Ani

AU - Brodsky, Matthew

AU - Ondo, William G.

AU - Hunter, Christine B.

AU - Jimenez-Shahed, Joohi

AU - Palao, Alicia

AU - Miyasaki, Janis M.

AU - So, Julie

AU - Tetrud, James

AU - Reys, Liza

AU - Smith, Katharine

AU - Singer, Carlos

AU - Blenke, Anita

AU - Russell, David S.

AU - Cotto, Candace

AU - Friedman, Joseph H.

AU - Lannon, Margaret

AU - Zhang, Lin

AU - Drasby, Edward

AU - Wojcieszek, Joanne

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

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