A randomized, double-blind, placebo-controlled trial of coenzyme Q10 in Huntington disease

Andrew McGarry, Michael McDermott, Karl Kieburtz, Elisabeth A. DeBlieck, Flint Beal, Karen Marder, Christopher Ross, Ira Shoulson, Peter Gilbert, William M. Mallonee, Mark Guttman, Joanne Wojcieszek, Rajeev Kumar, Mark S. LeDoux, Mary Jenkins, H. Diana Rosas, Martha Nance, Kevin Biglan, Peter Como, Richard M. Dubinsky & 40 others Kathleen M. Shannon, Padraig O'Suilleabhain, Kelvin Chou, Francis Walker, Wayne Martin, Vicki L. Wheelock, Elizabeth McCusker, Joseph Jankovic, Carlos Singer, Juan Sanchez-Ramos, Burton Scott, Oksana Suchowersky, Stewart A. Factor, Donald S. Higgins, Eric Molho, Fredy Revilla, John N. Caviness, Joseph H. Friedman, Joel S. Perlmutter, Andrew Feigin, Karen Anderson, Ramon Rodriguez, Nikolaus R. McFarland, Russell L. Margolis, Eric S. Farbman, Lynn A. Raymond, Valerie Suski, Sandra Kostyk, Amy Colcher, Lauren Seeberger, Eric Epping, Sherali Esmail, Nancy Diaz, Wai Lun Alan Fung, Alan Diamond, Samuel Frank, Philip Hanna, Neal Hermanowicz, Leon S. Dure, Merit Cudkowicz

Research output: Contribution to journalArticle

25 Citations (Scopus)

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 5 609) 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. ClinicalTrials.gov identifier: NCT00608881. Classification of evidence: This article provides Class I evidence that CoQ does not slow the progressive functional decline of patients with HD.

Original languageEnglish (US)
Pages (from-to)152-159
Number of pages8
JournalNeurology
Volume88
Issue number2
StatePublished - Jan 10 2017

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coenzyme Q10
Huntington Disease
Placebos
Medical Futility
Canada
Therapeutics
Joints
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Clinical Neurology

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McGarry, A., McDermott, M., Kieburtz, K., DeBlieck, E. A., Beal, F., Marder, K., ... Cudkowicz, M. (2017). A randomized, double-blind, placebo-controlled trial of coenzyme Q10 in Huntington disease. Neurology, 88(2), 152-159.

A randomized, double-blind, placebo-controlled trial of coenzyme Q10 in Huntington disease. / McGarry, Andrew; McDermott, Michael; Kieburtz, Karl; DeBlieck, Elisabeth A.; Beal, Flint; Marder, Karen; Ross, Christopher; Shoulson, Ira; Gilbert, Peter; Mallonee, William M.; Guttman, Mark; Wojcieszek, Joanne; Kumar, Rajeev; LeDoux, Mark S.; Jenkins, Mary; Rosas, H. Diana; Nance, Martha; Biglan, Kevin; Como, Peter; Dubinsky, Richard M.; Shannon, Kathleen M.; O'Suilleabhain, Padraig; Chou, Kelvin; Walker, Francis; Martin, Wayne; Wheelock, Vicki L.; McCusker, Elizabeth; Jankovic, Joseph; Singer, Carlos; Sanchez-Ramos, Juan; Scott, Burton; Suchowersky, Oksana; Factor, Stewart A.; Higgins, Donald S.; Molho, Eric; Revilla, Fredy; Caviness, John N.; Friedman, Joseph H.; Perlmutter, Joel S.; Feigin, Andrew; Anderson, Karen; Rodriguez, Ramon; McFarland, Nikolaus R.; Margolis, Russell L.; Farbman, Eric S.; Raymond, Lynn A.; Suski, Valerie; Kostyk, Sandra; Colcher, Amy; Seeberger, Lauren; Epping, Eric; Esmail, Sherali; Diaz, Nancy; Alan Fung, Wai Lun; Diamond, Alan; Frank, Samuel; Hanna, Philip; Hermanowicz, Neal; Dure, Leon S.; Cudkowicz, Merit.

In: Neurology, Vol. 88, No. 2, 10.01.2017, p. 152-159.

Research output: Contribution to journalArticle

McGarry, A, McDermott, M, Kieburtz, K, DeBlieck, EA, Beal, F, Marder, K, Ross, C, Shoulson, I, Gilbert, P, Mallonee, WM, Guttman, M, Wojcieszek, J, Kumar, R, LeDoux, MS, Jenkins, M, Rosas, HD, Nance, M, Biglan, K, Como, P, Dubinsky, RM, Shannon, KM, O'Suilleabhain, P, Chou, K, Walker, F, Martin, W, Wheelock, VL, McCusker, E, Jankovic, J, Singer, C, Sanchez-Ramos, J, Scott, B, Suchowersky, O, Factor, SA, Higgins, DS, Molho, E, Revilla, F, Caviness, JN, Friedman, JH, Perlmutter, JS, Feigin, A, Anderson, K, Rodriguez, R, McFarland, NR, Margolis, RL, Farbman, ES, Raymond, LA, Suski, V, Kostyk, S, Colcher, A, Seeberger, L, Epping, E, Esmail, S, Diaz, N, Alan Fung, WL, Diamond, A, Frank, S, Hanna, P, Hermanowicz, N, Dure, LS & Cudkowicz, M 2017, 'A randomized, double-blind, placebo-controlled trial of coenzyme Q10 in Huntington disease', Neurology, vol. 88, no. 2, pp. 152-159.
McGarry A, McDermott M, Kieburtz K, DeBlieck EA, Beal F, Marder K et al. A randomized, double-blind, placebo-controlled trial of coenzyme Q10 in Huntington disease. Neurology. 2017 Jan 10;88(2):152-159.
McGarry, Andrew ; McDermott, Michael ; Kieburtz, Karl ; DeBlieck, Elisabeth A. ; Beal, Flint ; Marder, Karen ; Ross, Christopher ; Shoulson, Ira ; Gilbert, Peter ; Mallonee, William M. ; Guttman, Mark ; Wojcieszek, Joanne ; Kumar, Rajeev ; LeDoux, Mark S. ; Jenkins, Mary ; Rosas, H. Diana ; Nance, Martha ; Biglan, Kevin ; Como, Peter ; Dubinsky, Richard M. ; Shannon, Kathleen M. ; O'Suilleabhain, Padraig ; Chou, Kelvin ; Walker, Francis ; Martin, Wayne ; Wheelock, Vicki L. ; McCusker, Elizabeth ; Jankovic, Joseph ; Singer, Carlos ; Sanchez-Ramos, Juan ; Scott, Burton ; Suchowersky, Oksana ; Factor, Stewart A. ; Higgins, Donald S. ; Molho, Eric ; Revilla, Fredy ; Caviness, John N. ; Friedman, Joseph H. ; Perlmutter, Joel S. ; Feigin, Andrew ; Anderson, Karen ; Rodriguez, Ramon ; McFarland, Nikolaus R. ; Margolis, Russell L. ; Farbman, Eric S. ; Raymond, Lynn A. ; Suski, Valerie ; Kostyk, Sandra ; Colcher, Amy ; Seeberger, Lauren ; Epping, Eric ; Esmail, Sherali ; Diaz, Nancy ; Alan Fung, Wai Lun ; Diamond, Alan ; Frank, Samuel ; Hanna, Philip ; Hermanowicz, Neal ; Dure, Leon S. ; Cudkowicz, Merit. / A randomized, double-blind, placebo-controlled trial of coenzyme Q10 in Huntington disease. In: Neurology. 2017 ; Vol. 88, No. 2. pp. 152-159.
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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 5 609) 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. ClinicalTrials.gov identifier: NCT00608881. Classification of evidence: This article provides Class I evidence that CoQ does not slow the progressive functional decline of patients with HD.",
author = "Andrew McGarry and Michael McDermott and Karl Kieburtz and DeBlieck, {Elisabeth A.} and Flint Beal and Karen Marder and Christopher Ross and Ira Shoulson and Peter Gilbert and Mallonee, {William M.} and Mark Guttman and Joanne Wojcieszek and Rajeev Kumar and LeDoux, {Mark S.} and Mary Jenkins and Rosas, {H. Diana} and Martha Nance and Kevin Biglan and Peter Como and Dubinsky, {Richard M.} and Shannon, {Kathleen M.} and Padraig O'Suilleabhain and Kelvin Chou and Francis Walker and Wayne Martin and Wheelock, {Vicki L.} and Elizabeth McCusker and Joseph Jankovic and Carlos Singer and Juan Sanchez-Ramos and Burton Scott and Oksana Suchowersky and Factor, {Stewart A.} and Higgins, {Donald S.} and Eric Molho and Fredy Revilla and Caviness, {John N.} and Friedman, {Joseph H.} and Perlmutter, {Joel S.} and Andrew Feigin and Karen Anderson and Ramon Rodriguez and McFarland, {Nikolaus R.} and Margolis, {Russell L.} and Farbman, {Eric S.} and Raymond, {Lynn A.} and Valerie Suski and Sandra Kostyk and Amy Colcher and Lauren Seeberger and Eric Epping and Sherali Esmail and Nancy Diaz and {Alan Fung}, {Wai Lun} and Alan Diamond and Samuel Frank and Philip Hanna and Neal Hermanowicz and Dure, {Leon S.} and Merit Cudkowicz",
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AU - McGarry, Andrew

AU - McDermott, Michael

AU - Kieburtz, Karl

AU - DeBlieck, Elisabeth A.

AU - Beal, Flint

AU - Marder, Karen

AU - Ross, Christopher

AU - Shoulson, Ira

AU - Gilbert, Peter

AU - Mallonee, William M.

AU - Guttman, Mark

AU - Wojcieszek, Joanne

AU - Kumar, Rajeev

AU - LeDoux, Mark S.

AU - Jenkins, Mary

AU - Rosas, H. Diana

AU - Nance, Martha

AU - Biglan, Kevin

AU - Como, Peter

AU - Dubinsky, Richard M.

AU - Shannon, Kathleen M.

AU - O'Suilleabhain, Padraig

AU - Chou, Kelvin

AU - Walker, Francis

AU - Martin, Wayne

AU - Wheelock, Vicki L.

AU - McCusker, Elizabeth

AU - Jankovic, Joseph

AU - Singer, Carlos

AU - Sanchez-Ramos, Juan

AU - Scott, Burton

AU - Suchowersky, Oksana

AU - Factor, Stewart A.

AU - Higgins, Donald S.

AU - Molho, Eric

AU - Revilla, Fredy

AU - Caviness, John N.

AU - Friedman, Joseph H.

AU - Perlmutter, Joel S.

AU - Feigin, Andrew

AU - Anderson, Karen

AU - Rodriguez, Ramon

AU - McFarland, Nikolaus R.

AU - Margolis, Russell L.

AU - Farbman, Eric S.

AU - Raymond, Lynn A.

AU - Suski, Valerie

AU - Kostyk, Sandra

AU - Colcher, Amy

AU - Seeberger, Lauren

AU - Epping, Eric

AU - Esmail, Sherali

AU - Diaz, Nancy

AU - Alan Fung, Wai Lun

AU - Diamond, Alan

AU - Frank, Samuel

AU - Hanna, Philip

AU - Hermanowicz, Neal

AU - Dure, Leon S.

AU - Cudkowicz, Merit

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N2 - 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 5 609) 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. ClinicalTrials.gov identifier: NCT00608881. Classification of evidence: This article provides Class I evidence that CoQ does not slow the progressive functional decline of patients with HD.

AB - 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 5 609) 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. ClinicalTrials.gov 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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