학술논문
Effect of creatine monohydrate on clinical progression in patients with Parkinson disease: a randomized clinical trial.
Document Type
article
Author
Writing Group for the NINDS Exploratory Trials in Parkinson Disease (NET-PD) Investigators; 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; Liang, Grace S Lin; Luo, Sheng T; Mari, Zoltan; Morgan, John C; 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
Source
JAMA. 313(6)
Subject
Language
Abstract
ImportanceThere 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.ObjectiveTo determine whether creatine monohydrate was more effective than placebo in slowing long-term clinical decline in participants with Parkinson disease.Design, setting, and patientsThe 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.InterventionsParticipants were randomized to placebo or creatine (10 g/d) monohydrate for a minimum of 5 years (maximum follow-up, 8 years).Main outcomes and measuresThe primary outcome measure was 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.ResultsThe 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