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Evidence of Slowing of the Functional Decline

Clifford W. Shults, MD; David Oakes, PhD; Karl Kieburtz, MD; M. Flint Beal, MD; Richard Haas, MB Chir; Sandy Plumb, BS; Jorge L. Juncos, MD; John Nutt, MD; Ira Shoulson, MD; Julie Carter, RN, MS, ANP; Katie Kompoliti, MD; Joel S Perlmutter, MD; Stephen Reich, MD; Matthew Stern, MD; Ray L. Watts, MD; Roger Kurlan, MD; Eric Molho, MD; Madaline Harrison, MD; Mark Lew, MD; and the Parkinson Study Group

Arch Neurol. 2002;59:1541-1550.

Background  Parkinson disease (PD) is a degenerative neurological disorder for which no treatment has been shown to slow the progression.

Objective  To determine whether a range of dosages of coenzyme Q₁₀ is safe and well tolerated and could slow the functional decline in PD.

Design  Multicenter, randomized, parallel-group, placebo-controlled, double-blind, dosage-ranging trial.

Setting  Academic movement disorders clinics.

Patients  Eighty subjects with early PD who did not require treatment for their disability.

Interventions  Random assignment to placebo or coenzyme Q₁₀ at dosages of 300, 600, or 1200 mg/d.

Main Outcome Measure  The subjects underwent evaluation with the Unified Parkinson Disease Rating Scale (UPDRS) at the screening, baseline, and 1-, 4-, 8-, 12-, and 16-month visits. They were followed up for 16 months or until disability requiring treatment with levodopa had developed. The primary response variable was the change in the total score on the UPDRS from baseline to the last visit.

Results  The adjusted mean total UPDRS changes were +11.99 for the placebo group, +8.81 for the 300-mg/d group, +10.82 for the 600-mg/d group, and +6.69 for the 1200-mg/d group. The P value for the primary analysis, a test for a linear trend between the dosage and the mean change in the total UPDRS score, was .09, which met our prespecified criteria for a positive trend for the trial. A prespecified, secondary analysis was the comparison of each treatment group with the placebo group, and the difference between the 1200-mg/d and placebo groups was significant (P = .04).

Conclusions  Coenzyme Q₁₀ was safe and well tolerated at dosages of up to 1200 mg/d. Less disability developed in subjects assigned to coenzyme Q₁₀ than in those assigned to placebo, and the benefit was greatest in subjects receiving the highest dosage. Coenzyme Q₁₀ appears to slow the progressive deterioration of function in PD, but these results need to be confirmed in a larger study.

From the Department of Neurosciences, University of California–San Diego, La Jolla (Drs Shults and Haas); Veterans Affairs San Diego Healthcare System, San Diego (Dr Shults); Departments of Biostatistics (Dr Oakes) and Neurology (Drs Kieburtz, Shoulson, and Kurlan and Ms Plumb), University of Rochester School of Medicine and Dentistry, Rochester, NY; Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY (Dr Beal); Department of Neurology and Wesley Woods Center, Emory University, Atlanta, Ga (Drs Juncos and Watts); Parkinson's Disease Research, Education and Clinical Center–Veterans Affairs Medical Center (Dr Nutt) and Oregon Health and Science University (Dr Nutt and Ms Carter), Portland; and the Departments of Neurology, Rush Presbyterian/St. Luke's Medical Center, Chicago, Ill (Dr Kompoliti), Washington University, St. Louis, Mo (Dr Perlmutter), The Johns Hopkins University, Baltimore, Md (Dr Reich), University of Pennsylvania and Parkinson's Disease Research, Education and Clinical Center–Veterans Affairs Medical Center, Philadelphia (Dr Stern), Albany Medical College, Albany, NY (Dr Molho), University of Virginia, Charlottesville (Dr Harrison), and University of Southern California, Los Angeles (Dr Lew). Dr Shults and Mr Meese are coinventors in a pending patent application. The application is jointly owned by Enzymatic Therapy, Inc, Green Bay, Wis (owner of Vitaline Corp, Ashland, Ore), and The Regents of the University of California.

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