Effect of creatine monohydrate on clinical progression in patients with parkinson disease

A randomized clinical trial

Karl Kieburtz, Barbara C. Tilley, Jordan J. Elm, Debra Babcock, Robert Hauser, G. Webster Ross, Alicia H. Augustine, Erika U. Augustine, Michael J. Aminoff, Ivan G. Bodis-Wollner, James Boyd, Franca Cambi, Kelvin Chou, Chadwick W. Christine, Michelle Cines, Nabila Dahodwala, Lorelei Derwent, Richard B. Dewey, Katherine Hawthorne, David J. Houghton & 23 others Cornelia Kamp, Maureen Leehey, Mark F. Lew, Grace S. Lin Liang, Sheng T. Luo, Zoltan Mari, John Christopher Morgan, Sotirios Parashos, Adriana Pérez, Helen Petrovitch, Suja Rajan, Sue Reichwein, Jessie Tatsuno Roth, Jay S. Schneider, Kathleen M. Shannon, David K. Simon, Tanya Simuni, Carlos Singer, Lewis Sudarsky, Caroline M. Tanner, Chizoba C. Umeh, Karen Williams, Anne Marie Wills

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

Importance: There are no treatments available to slow or prevent the progression of Parkinson disease, despite its global prevalence and significant health care burden. The National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson Disease program was established to promote discovery of potential therapies. Objective: To determine whether creatine monohydrate was more effective than placebo in slowing long-term clinical decline in participants with Parkinson disease. Design, Setting, and Patients: The Long-term Study 1, a multicenter, double-blind, parallel-group, placebo-controlled, 1:1 randomized efficacy trial. Participants were recruited from 45 investigative sites in the United States and Canada and included 1741 men and women with early (within 5 years of diagnosis) and treated (receiving dopaminergic therapy) Parkinson disease. Participants were enrolled from March 2007 to May 2010 and followed up until September 2013. Interventions: Participants were randomized to placebo or creatine (10 g/d) monohydrate for a minimum of 5 years (maximum follow-up, 8 years). Main Outcomes and Measures: The primary outcome measurewas a difference in clinical decline from baseline to 5-year follow-up, compared between the 2 treatment groups using a global statistical test. Clinical status was defined by 5 outcome measures: Modified Rankin Scale, Symbol Digit Modalities Test, PDQ-39 Summary Index, Schwab and England Activities of Daily Living scale, and ambulatory capacity. All outcomes were coded such that higher scores indicated worse outcomes and were analyzed by a global statistical test. Higher summed ranks (range, 5-4775) indicate worse outcomes. Results : The trial was terminated early for futility based on results of a planned interim analysis of participants enrolled at least 5 years prior to the date of the analysis (n = 955). The median follow-up time was 4 years. Of the 955 participants, the mean of the summed ranks for placebo was 2360 (95%CI, 2249-2470) and for creatine was 2414 (95%CI, 2304-2524). The global statistical test yielded t1865.8 =-0.75 (2-sided P = .45). There were no detectable differences (P < .01 to partially adjust for multiple comparisons) in adverse and serious adverse events by body system. Conclusions: AND RELEVANCE Among patients with early and treated Parkinson disease, treatment with creatine monohydrate for at least 5 years, compared with placebo did not improve clinical outcomes. These findings do not support the use of creatine monohydrate in patients with Parkinson disease.

Original languageEnglish (US)
Pages (from-to)584-593
Number of pages10
JournalJAMA - Journal of the American Medical Association
Volume313
Issue number6
DOIs
StatePublished - Feb 10 2015

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Creatine
Parkinson Disease
Randomized Controlled Trials
Placebos
National Institute of Neurological Disorders and Stroke
Outcome Assessment (Health Care)
Medical Futility
Therapeutics
Activities of Daily Living
England
Canada
Delivery of Health Care

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Effect of creatine monohydrate on clinical progression in patients with parkinson disease : A randomized clinical trial. / Kieburtz, Karl; Tilley, Barbara C.; Elm, Jordan J.; Babcock, Debra; Hauser, Robert; Ross, G. Webster; Augustine, Alicia H.; Augustine, Erika U.; Aminoff, Michael J.; Bodis-Wollner, Ivan G.; Boyd, James; Cambi, Franca; Chou, Kelvin; Christine, Chadwick W.; Cines, Michelle; Dahodwala, Nabila; Derwent, Lorelei; Dewey, Richard B.; Hawthorne, Katherine; Houghton, David J.; Kamp, Cornelia; Leehey, Maureen; Lew, Mark F.; Lin Liang, Grace S.; Luo, Sheng T.; Mari, Zoltan; Morgan, John Christopher; Parashos, Sotirios; Pérez, Adriana; Petrovitch, Helen; Rajan, Suja; Reichwein, Sue; Roth, Jessie Tatsuno; Schneider, Jay S.; Shannon, Kathleen M.; Simon, David K.; Simuni, Tanya; Singer, Carlos; Sudarsky, Lewis; Tanner, Caroline M.; Umeh, Chizoba C.; Williams, Karen; Wills, Anne Marie.

In: JAMA - Journal of the American Medical Association, Vol. 313, No. 6, 10.02.2015, p. 584-593.

Research output: Contribution to journalArticle

Kieburtz, K, Tilley, BC, Elm, JJ, Babcock, D, Hauser, R, Ross, GW, Augustine, AH, Augustine, EU, Aminoff, MJ, Bodis-Wollner, IG, Boyd, J, Cambi, F, Chou, K, Christine, CW, Cines, M, Dahodwala, N, Derwent, L, Dewey, RB, Hawthorne, K, Houghton, DJ, Kamp, C, Leehey, M, Lew, MF, Lin Liang, GS, Luo, ST, Mari, Z, Morgan, JC, Parashos, S, Pérez, A, Petrovitch, H, Rajan, S, Reichwein, S, Roth, JT, Schneider, JS, Shannon, KM, Simon, DK, Simuni, T, Singer, C, Sudarsky, L, Tanner, CM, Umeh, CC, Williams, K & Wills, AM 2015, 'Effect of creatine monohydrate on clinical progression in patients with parkinson disease: A randomized clinical trial', JAMA - Journal of the American Medical Association, vol. 313, no. 6, pp. 584-593. https://doi.org/10.1001/jama.2015.120
Kieburtz, Karl ; Tilley, Barbara C. ; Elm, Jordan J. ; Babcock, Debra ; Hauser, Robert ; Ross, G. Webster ; Augustine, Alicia H. ; Augustine, Erika U. ; Aminoff, Michael J. ; Bodis-Wollner, Ivan G. ; Boyd, James ; Cambi, Franca ; Chou, Kelvin ; Christine, Chadwick W. ; Cines, Michelle ; Dahodwala, Nabila ; Derwent, Lorelei ; Dewey, Richard B. ; Hawthorne, Katherine ; Houghton, David J. ; Kamp, Cornelia ; Leehey, Maureen ; Lew, Mark F. ; Lin Liang, Grace S. ; Luo, Sheng T. ; Mari, Zoltan ; Morgan, John Christopher ; Parashos, Sotirios ; Pérez, Adriana ; Petrovitch, Helen ; Rajan, Suja ; Reichwein, Sue ; Roth, Jessie Tatsuno ; Schneider, Jay S. ; Shannon, Kathleen M. ; Simon, David K. ; Simuni, Tanya ; Singer, Carlos ; Sudarsky, Lewis ; Tanner, Caroline M. ; Umeh, Chizoba C. ; Williams, Karen ; Wills, Anne Marie. / Effect of creatine monohydrate on clinical progression in patients with parkinson disease : A randomized clinical trial. In: JAMA - Journal of the American Medical Association. 2015 ; Vol. 313, No. 6. pp. 584-593.
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abstract = "Importance: There are no treatments available to slow or prevent the progression of Parkinson disease, despite its global prevalence and significant health care burden. The National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson Disease program was established to promote discovery of potential therapies. Objective: To determine whether creatine monohydrate was more effective than placebo in slowing long-term clinical decline in participants with Parkinson disease. Design, Setting, and Patients: The Long-term Study 1, a multicenter, double-blind, parallel-group, placebo-controlled, 1:1 randomized efficacy trial. Participants were recruited from 45 investigative sites in the United States and Canada and included 1741 men and women with early (within 5 years of diagnosis) and treated (receiving dopaminergic therapy) Parkinson disease. Participants were enrolled from March 2007 to May 2010 and followed up until September 2013. Interventions: Participants were randomized to placebo or creatine (10 g/d) monohydrate for a minimum of 5 years (maximum follow-up, 8 years). Main Outcomes and Measures: The primary outcome measurewas a difference in clinical decline from baseline to 5-year follow-up, compared between the 2 treatment groups using a global statistical test. Clinical status was defined by 5 outcome measures: Modified Rankin Scale, Symbol Digit Modalities Test, PDQ-39 Summary Index, Schwab and England Activities of Daily Living scale, and ambulatory capacity. All outcomes were coded such that higher scores indicated worse outcomes and were analyzed by a global statistical test. Higher summed ranks (range, 5-4775) indicate worse outcomes. Results : The trial was terminated early for futility based on results of a planned interim analysis of participants enrolled at least 5 years prior to the date of the analysis (n = 955). The median follow-up time was 4 years. Of the 955 participants, the mean of the summed ranks for placebo was 2360 (95{\%}CI, 2249-2470) and for creatine was 2414 (95{\%}CI, 2304-2524). The global statistical test yielded t1865.8 =-0.75 (2-sided P = .45). There were no detectable differences (P < .01 to partially adjust for multiple comparisons) in adverse and serious adverse events by body system. Conclusions: AND RELEVANCE Among patients with early and treated Parkinson disease, treatment with creatine monohydrate for at least 5 years, compared with placebo did not improve clinical outcomes. These findings do not support the use of creatine monohydrate in patients with Parkinson disease.",
author = "Karl Kieburtz and Tilley, {Barbara C.} and Elm, {Jordan J.} and Debra Babcock and Robert Hauser and Ross, {G. Webster} and Augustine, {Alicia H.} and Augustine, {Erika U.} and Aminoff, {Michael J.} and Bodis-Wollner, {Ivan G.} and James Boyd and Franca Cambi and Kelvin Chou and Christine, {Chadwick W.} and Michelle Cines and Nabila Dahodwala and Lorelei Derwent and Dewey, {Richard B.} and Katherine Hawthorne and Houghton, {David J.} and Cornelia Kamp and Maureen Leehey and Lew, {Mark F.} and {Lin Liang}, {Grace S.} and Luo, {Sheng T.} and Zoltan Mari and Morgan, {John Christopher} and Sotirios Parashos and Adriana P{\'e}rez and Helen Petrovitch and Suja Rajan and Sue Reichwein and Roth, {Jessie Tatsuno} and Schneider, {Jay S.} and Shannon, {Kathleen M.} and Simon, {David K.} and Tanya Simuni and Carlos Singer and Lewis Sudarsky and Tanner, {Caroline M.} and Umeh, {Chizoba C.} and Karen Williams and Wills, {Anne Marie}",
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TY - JOUR

T1 - Effect of creatine monohydrate on clinical progression in patients with parkinson disease

T2 - A randomized clinical trial

AU - Kieburtz, Karl

AU - Tilley, Barbara C.

AU - Elm, Jordan J.

AU - Babcock, Debra

AU - Hauser, Robert

AU - Ross, G. Webster

AU - Augustine, Alicia H.

AU - Augustine, Erika U.

AU - Aminoff, Michael J.

AU - Bodis-Wollner, Ivan G.

AU - Boyd, James

AU - Cambi, Franca

AU - Chou, Kelvin

AU - Christine, Chadwick W.

AU - Cines, Michelle

AU - Dahodwala, Nabila

AU - Derwent, Lorelei

AU - Dewey, Richard B.

AU - Hawthorne, Katherine

AU - Houghton, David J.

AU - Kamp, Cornelia

AU - Leehey, Maureen

AU - Lew, Mark F.

AU - Lin Liang, Grace S.

AU - Luo, Sheng T.

AU - Mari, Zoltan

AU - Morgan, John Christopher

AU - Parashos, Sotirios

AU - Pérez, Adriana

AU - Petrovitch, Helen

AU - Rajan, Suja

AU - Reichwein, Sue

AU - Roth, Jessie Tatsuno

AU - Schneider, Jay S.

AU - Shannon, Kathleen M.

AU - Simon, David K.

AU - Simuni, Tanya

AU - Singer, Carlos

AU - Sudarsky, Lewis

AU - Tanner, Caroline M.

AU - Umeh, Chizoba C.

AU - Williams, Karen

AU - Wills, Anne Marie

PY - 2015/2/10

Y1 - 2015/2/10

N2 - Importance: There are no treatments available to slow or prevent the progression of Parkinson disease, despite its global prevalence and significant health care burden. The National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson Disease program was established to promote discovery of potential therapies. Objective: To determine whether creatine monohydrate was more effective than placebo in slowing long-term clinical decline in participants with Parkinson disease. Design, Setting, and Patients: The Long-term Study 1, a multicenter, double-blind, parallel-group, placebo-controlled, 1:1 randomized efficacy trial. Participants were recruited from 45 investigative sites in the United States and Canada and included 1741 men and women with early (within 5 years of diagnosis) and treated (receiving dopaminergic therapy) Parkinson disease. Participants were enrolled from March 2007 to May 2010 and followed up until September 2013. Interventions: Participants were randomized to placebo or creatine (10 g/d) monohydrate for a minimum of 5 years (maximum follow-up, 8 years). Main Outcomes and Measures: The primary outcome measurewas a difference in clinical decline from baseline to 5-year follow-up, compared between the 2 treatment groups using a global statistical test. Clinical status was defined by 5 outcome measures: Modified Rankin Scale, Symbol Digit Modalities Test, PDQ-39 Summary Index, Schwab and England Activities of Daily Living scale, and ambulatory capacity. All outcomes were coded such that higher scores indicated worse outcomes and were analyzed by a global statistical test. Higher summed ranks (range, 5-4775) indicate worse outcomes. Results : The trial was terminated early for futility based on results of a planned interim analysis of participants enrolled at least 5 years prior to the date of the analysis (n = 955). The median follow-up time was 4 years. Of the 955 participants, the mean of the summed ranks for placebo was 2360 (95%CI, 2249-2470) and for creatine was 2414 (95%CI, 2304-2524). The global statistical test yielded t1865.8 =-0.75 (2-sided P = .45). There were no detectable differences (P < .01 to partially adjust for multiple comparisons) in adverse and serious adverse events by body system. Conclusions: AND RELEVANCE Among patients with early and treated Parkinson disease, treatment with creatine monohydrate for at least 5 years, compared with placebo did not improve clinical outcomes. These findings do not support the use of creatine monohydrate in patients with Parkinson disease.

AB - Importance: There are no treatments available to slow or prevent the progression of Parkinson disease, despite its global prevalence and significant health care burden. The National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson Disease program was established to promote discovery of potential therapies. Objective: To determine whether creatine monohydrate was more effective than placebo in slowing long-term clinical decline in participants with Parkinson disease. Design, Setting, and Patients: The Long-term Study 1, a multicenter, double-blind, parallel-group, placebo-controlled, 1:1 randomized efficacy trial. Participants were recruited from 45 investigative sites in the United States and Canada and included 1741 men and women with early (within 5 years of diagnosis) and treated (receiving dopaminergic therapy) Parkinson disease. Participants were enrolled from March 2007 to May 2010 and followed up until September 2013. Interventions: Participants were randomized to placebo or creatine (10 g/d) monohydrate for a minimum of 5 years (maximum follow-up, 8 years). Main Outcomes and Measures: The primary outcome measurewas a difference in clinical decline from baseline to 5-year follow-up, compared between the 2 treatment groups using a global statistical test. Clinical status was defined by 5 outcome measures: Modified Rankin Scale, Symbol Digit Modalities Test, PDQ-39 Summary Index, Schwab and England Activities of Daily Living scale, and ambulatory capacity. All outcomes were coded such that higher scores indicated worse outcomes and were analyzed by a global statistical test. Higher summed ranks (range, 5-4775) indicate worse outcomes. Results : The trial was terminated early for futility based on results of a planned interim analysis of participants enrolled at least 5 years prior to the date of the analysis (n = 955). The median follow-up time was 4 years. Of the 955 participants, the mean of the summed ranks for placebo was 2360 (95%CI, 2249-2470) and for creatine was 2414 (95%CI, 2304-2524). The global statistical test yielded t1865.8 =-0.75 (2-sided P = .45). There were no detectable differences (P < .01 to partially adjust for multiple comparisons) in adverse and serious adverse events by body system. Conclusions: AND RELEVANCE Among patients with early and treated Parkinson disease, treatment with creatine monohydrate for at least 5 years, compared with placebo did not improve clinical outcomes. These findings do not support the use of creatine monohydrate in patients with Parkinson disease.

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