Effect of creatine monohydrate on clinical progression in patients with Parkinson disease: a randomized clinical trial
Writing Group for the NINDS Exploratory Trials in Parkinson Disease (NET-PD) Investigators, 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, 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
JAMA · 180 citations
How it was studied
- Design
- Randomized controlled trial (indexed by PubMed)
- Studied in
- People
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Independent funding
- Government
- National Institute on Aging
- Government
- National Institute of Neurological Disorders and Stroke
- Government
- National Center for Research Resources
- Government
- National Center for Advancing Translational Sciences
- Government
- National Institute on Minority Health and Health Disparities
- Government
- NINDS NIH HHS
- Government
- NIMHD NIH HHS
- Government
- NIA NIH HHS
- Government
- NCATS NIH HHS
- Government
- NCRR NIH HHS
- Grants
- National Institute of Neurological Disorders and Stroke (U10 NS044504); National Institute of Neurological Disorders and Stroke (K-12NS 066098); National Center for Advancing Translational Sciences (UL1 TR000433); National Center for Research Resources (UL1 RR 025758); National Institute on Aging (K23AG034236); National Institute of Neurological Disorders and Stroke (P50NS091856); National Institute of Neurological Disorders and Stroke (K23 NS072283); National Institute of Neurological Disorders and Stroke (U10 NS044545); National Institute of Neurological Disorders and Stroke (U01 NS43128); National Institute of Neurological Disorders and Stroke (U01NS 043128); National Institute on Minority Health and Health Disparities (R24 MD001779); National Institute of Neurological Disorders and Stroke (NS44504-08); National Institute of Neurological Disorders and Stroke (U10 NS044460)
Based on 10 listed funder(s).
Publication
- Published
- 2015-02-10 · JAMA · vol. 313 · issue 6 · p. 584
- Publisher
- American Medical Association
- Cited
- 242 citations · more than 100% of similar papers · 18.9× the field average
- Impact
- Top 10% most cited in its field
- References
- 32 works
- Access
- Open access (repository copy)
- Research areas
- Parkinson's Disease Mechanisms and Treatments · Muscle metabolism and nutrition · Nutrition and Health in Aging
- Keywords
- Medicine, Physical therapy, Randomized controlled trial, Clinical trial, Placebo, Ambulatory, Creatine, Internal medicine, Pediatrics, Alternative medicine, Pathology
- MeSH
- humans, parkinson disease, disease progression, creatine, antiparkinson agents, treatment outcome, drug therapy, combination, follow-up studies, double-blind method, aged, middle aged, female, male, medication adherence
43 authors
From US, CA
- Karl Kieburtz · correspondingUniversity of Rochester
- Barbara C. TilleyThe University of Texas Health Science Center at Houston
- Jordan J. ElmMedical University of South Carolina
- Debra BabcockNational Institutes of Health
- Robert A. HauserUniversity of South Florida
- G. Webster RossPacific Health Research and Education Institute
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 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.
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.
Trial registration
clinicaltrials.gov Identifier: NCT00449865.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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