Andrew McGarry1, Michael McDermott2, Karl Kieburtz2, Elisabeth A de Blieck2, Flint Beal2, Karen Marder2, Christopher Ross2, Ira Shoulson2, Peter Gilbert2, William M Mallonee2, Mark Guttman2, Joanne Wojcieszek2, Rajeev Kumar2, Mark S LeDoux2, Mary Jenkins2, H Diana Rosas2, Martha Nance2, Kevin Biglan2, Peter Como2, Richard M Dubinsky2, Kathleen M Shannon2, Padraig O'Suilleabhain2, Kelvin Chou2, Francis Walker2, Wayne Martin2, Vicki L Wheelock2, Elizabeth McCusker2, Joseph Jankovic2, Carlos Singer2, Juan Sanchez-Ramos2, Burton Scott2, Oksana Suchowersky2, Stewart A Factor2, Donald S Higgins2, Eric Molho2, Fredy Revilla2, John N Caviness2, Joseph H Friedman2, Joel S Perlmutter2, Andrew Feigin2, Karen Anderson2, Ramon Rodriguez2, Nikolaus R McFarland2, Russell L Margolis2, Eric S Farbman2, Lynn A Raymond2, Valerie Suski2, Sandra Kostyk2, Amy Colcher2, Lauren Seeberger2, Eric Epping2, Sherali Esmail2, Nancy Diaz2, Wai Lun Alan Fung2, Alan Diamond2, Samuel Frank2, Philip Hanna2, Neal Hermanowicz2, Leon S Dure2, Merit Cudkowicz2. 1. From Cooper University Healthcare at Rowan University (A.M.), Camden, NJ; University of Rochester (M.M., K.K., E.A.d.B., K.B., P.C.); Weill Cornell Medical Center (F.B.); Columbia Presbyterian Medical Center (K.M.), New York, NY; Johns Hopkins Medical Center (C.R.), Baltimore, MD; Georgetown University (I.S.), Washington, DC; NINDS (P.G.), Bethesda, MD; Hereditary Neurological Disease Center (W.M.M.), Wichita, KS; The Centre for Movement Disorders (M.G.), Toronto, Canada; Indiana University School of Medicine (J.W.), Indianapolis; Colorado Neurological Institute (R.K.), Englewood; University of Tennessee Health Science Center (M.S.L.), Memphis; London Health Sciences Centre (M.J.), Canada; Massachusetts General Hospital (H.D.R.), Boston; Struthers Parkinson's Center (M.N.), Minneapolis, MN; University of Kansas Medical Center (R.M.D.), Kansas City; Rush University Medical Center (K.M.S.), Chicago, IL; University of Texas Southwestern Medical Center (P.O.), Dallas; University of Michigan (K.C.), Ann Arbor; Wake Forest University (F.W.), Winston-Salem, NC; University of Alberta (W.M.), Edmonton, Canada; University of California Davis (V.L.W.), Sacramento; Westmead Hospital (E. McCusker), Westmead, Australia; Baylor College of Medicine (J.J.), Houston, TX; University of Miami Miller School of Medicine (C.S.), FL; University of South Florida (J.S.-R.), Tampa; Duke University (B.S.), Durham, NC; University of Calgary (O.S.), Canada; Emory University School of Medicine (S.A.F.), Atlanta, GA; Albany Medical College (D.S.H., Eric Molho), NY; University of Cincinnati (F.R.), OH; Mayo Clinic Arizona (J.N.C.), Scottsdale; Butler Hospital (J.H.F.), Providence, RI; Washington University (J.S.P.), St. Louis, MO; Feinstein Institute for Medical Research (A.F.), Manhasset, NY; Georgetown University (K.A.), Washington, DC; University of Florida (R.R., N.R.M.), Gainesville; Johns Hopkins University (R.L.M.), Baltimore, MD; University of Nevada School of Medicine (E.S.F.), Reno; University of British Columbia (L.A.R.), Vancouver, Canada; University of Pittsburgh (V.S.), PA; Ohio State University (S.K.), Columbus; The Cooper University Health System (A.C.), Camden, NJ; Idaho Elks Rehabilitation Hospital (L.S.), Boise, ID; University of Iowa (E.E.), Iowa City; North York General Hospital 1 (S.E.), Toronto, Canada; St. Luke's Hospital (N.D.), Allentown, PA; North York General Hospital 2 (W.L.A.F.), University of Toronto, Canada; Washington Regional Medical Center (A.D.), Fayetteville, AR; Beth-Israel Deaconess Medical Center (S.F.), Boston, MA; NJ Neuroscience Institute (P.H.), Edison; University of California Irvine (N.H.); The University of Alabama at Birmingham (L.S.D.); and Massachusetts General Hospital (M.C.), Harvard Medical School, Boston. mcgarry-andrew@cooperhealth.edu. 2. From Cooper University Healthcare at Rowan University (A.M.), Camden, NJ; University of Rochester (M.M., K.K., E.A.d.B., K.B., P.C.); Weill Cornell Medical Center (F.B.); Columbia Presbyterian Medical Center (K.M.), New York, NY; Johns Hopkins Medical Center (C.R.), Baltimore, MD; Georgetown University (I.S.), Washington, DC; NINDS (P.G.), Bethesda, MD; Hereditary Neurological Disease Center (W.M.M.), Wichita, KS; The Centre for Movement Disorders (M.G.), Toronto, Canada; Indiana University School of Medicine (J.W.), Indianapolis; Colorado Neurological Institute (R.K.), Englewood; University of Tennessee Health Science Center (M.S.L.), Memphis; London Health Sciences Centre (M.J.), Canada; Massachusetts General Hospital (H.D.R.), Boston; Struthers Parkinson's Center (M.N.), Minneapolis, MN; University of Kansas Medical Center (R.M.D.), Kansas City; Rush University Medical Center (K.M.S.), Chicago, IL; University of Texas Southwestern Medical Center (P.O.), Dallas; University of Michigan (K.C.), Ann Arbor; Wake Forest University (F.W.), Winston-Salem, NC; University of Alberta (W.M.), Edmonton, Canada; University of California Davis (V.L.W.), Sacramento; Westmead Hospital (E. McCusker), Westmead, Australia; Baylor College of Medicine (J.J.), Houston, TX; University of Miami Miller School of Medicine (C.S.), FL; University of South Florida (J.S.-R.), Tampa; Duke University (B.S.), Durham, NC; University of Calgary (O.S.), Canada; Emory University School of Medicine (S.A.F.), Atlanta, GA; Albany Medical College (D.S.H., Eric Molho), NY; University of Cincinnati (F.R.), OH; Mayo Clinic Arizona (J.N.C.), Scottsdale; Butler Hospital (J.H.F.), Providence, RI; Washington University (J.S.P.), St. Louis, MO; Feinstein Institute for Medical Research (A.F.), Manhasset, NY; Georgetown University (K.A.), Washington, DC; University of Florida (R.R., N.R.M.), Gainesville; Johns Hopkins University (R.L.M.), Baltimore, MD; University of Nevada School of Medicine (E.S.F.), Reno; University of British Columbia (L.A.R.), Vancouver, Canada; University of Pittsburgh (V.S.), PA; Ohio State University (S.K.), Columbus; The Cooper University Health System (A.C.), Camden, NJ; Idaho Elks Rehabilitation Hospital (L.S.), Boise, ID; University of Iowa (E.E.), Iowa City; North York General Hospital 1 (S.E.), Toronto, Canada; St. Luke's Hospital (N.D.), Allentown, PA; North York General Hospital 2 (W.L.A.F.), University of Toronto, Canada; Washington Regional Medical Center (A.D.), Fayetteville, AR; Beth-Israel Deaconess Medical Center (S.F.), Boston, MA; NJ Neuroscience Institute (P.H.), Edison; University of California Irvine (N.H.); The University of Alabama at Birmingham (L.S.D.); and Massachusetts General Hospital (M.C.), Harvard Medical School, Boston.
Abstract
OBJECTIVE: To test the hypothesis that chronic treatment of early-stage Huntington disease (HD) with high-dose coenzyme Q10 (CoQ) will slow the progressive functional decline of HD. METHODS: We performed a multicenter randomized, double-blind, placebo-controlled trial. Patients with early-stage HD (n = 609) were enrolled at 48 sites in the United States, Canada, and Australia from 2008 to 2012. Patients were randomized to receive either CoQ 2,400 mg/d or matching placebo, then followed for 60 months. The primary outcome variable was the change from baseline to month 60 in Total Functional Capacity score (for patients who survived) combined with time to death (for patients who died) analyzed using a joint-rank analysis approach. RESULTS: An interim analysis for futility revealed a conditional power of <5% for the primary analysis, prompting premature conclusion in July 2014. No statistically significant differences were seen between treatment groups for the primary or secondary outcome measures. CoQ was generally safe and well-tolerated throughout the study. CONCLUSIONS: These data do not justify use of CoQ as a treatment to slow functional decline in HD. CLINICALTRIALSGOV IDENTIFIER: NCT00608881. CLASSIFICATION OF EVIDENCE: This article provides Class I evidence that CoQ does not slow the progressive functional decline of patients with HD.
OBJECTIVE: To test the hypothesis that chronic treatment of early-stage Huntington disease (HD) with high-dose coenzyme Q10 (CoQ) will slow the progressive functional decline of HD. METHODS: We performed a multicenter randomized, double-blind, placebo-controlled trial. Patients with early-stage HD (n = 609) were enrolled at 48 sites in the United States, Canada, and Australia from 2008 to 2012. Patients were randomized to receive either CoQ 2,400 mg/d or matching placebo, then followed for 60 months. The primary outcome variable was the change from baseline to month 60 in Total Functional Capacity score (for patients who survived) combined with time to death (for patients who died) analyzed using a joint-rank analysis approach. RESULTS: An interim analysis for futility revealed a conditional power of <5% for the primary analysis, prompting premature conclusion in July 2014. No statistically significant differences were seen between treatment groups for the primary or secondary outcome measures. CoQ was generally safe and well-tolerated throughout the study. CONCLUSIONS: These data do not justify use of CoQ as a treatment to slow functional decline in HD. CLINICALTRIALSGOV IDENTIFIER: NCT00608881. CLASSIFICATION OF EVIDENCE: This article provides Class I evidence that CoQ does not slow the progressive functional decline of patients with HD.
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