title: Effect of creatine monohydrate on clinical progression in patients with Parkinson disease: a randomized clinical trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  Participants were randomized to placebo or creatine (10 g/d) monohydrate for a minimum of 5 years (maximum follow-up, 8 years).
  
  
  METHODS
  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
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00449865.
authors: University of Rochester, Rochester, New York.
authors: Karl
authors: K
authors: Kieburtz
authors: University of Texas Health Science Center at Houston.
authors: Barbara C
authors: BC
authors: Tilley
authors: Medical University of South Carolina, Charleston.
authors: Jordan J
authors: JJ
authors: Elm
authors: National Institutes of Health, Bethesda, Maryland.
authors: Debra
authors: D
authors: Babcock
authors: University of South Florida, Tampa.
authors: Robert
authors: R
authors: Hauser
authors: Pacific Health Research and Education Institute, Honolulu, Hawaii.
authors: G Webster
authors: GW
authors: Ross
authors: University of Rochester, Rochester, New York.
authors: Alicia H
authors: AH
authors: Augustine
authors: University of Rochester, Rochester, New York.
authors: Erika U
authors: EU
authors: Augustine
authors: University of California, San Francisco.
authors: Michael J
authors: MJ
authors: Aminoff
authors: State University of New York Downstate Medical Center, Brooklyn.
authors: Ivan G
authors: IG
authors: Bodis-Wollner
authors: University of Vermont, Burlington.
authors: James
authors: J
authors: Boyd
authors: University of Kentucky, Lexington.
authors: Franca
authors: F
authors: Cambi
authors: University of Michigan, Ann Arbor.
authors: Kelvin
authors: K
authors: Chou
authors: University of California, San Francisco.
authors: Chadwick W
authors: CW
authors: Christine
authors: University of Maryland School of Medicine, Baltimore.
authors: Michelle
authors: M
authors: Cines
authors: University of Pennsylvania, Philadelphia.
authors: Nabila
authors: N
authors: Dahodwala
authors: University of Calgary, Calgary, Alberta, Canada.
authors: Lorelei
authors: L
authors: Derwent
authors: University of Texas Southwestern Medical Center, Dallas.
authors: Richard B
authors: RB
authors: Dewey
authors: University of Southern California, Los Angeles.
authors: Katherine
authors: K
authors: Hawthorne
authors: Ochsner Medical Center, New Orleans, Louisiana.
authors: David J
authors: DJ
authors: Houghton
authors: University of Rochester, Rochester, New York.
authors: Cornelia
authors: C
authors: Kamp
authors: University of Colorado Denver, Aurora.
authors: Maureen
authors: M
authors: Leehey
authors: University of Southern California, Los Angeles.
authors: Mark F
authors: MF
authors: Lew
authors: The Parkinson's Institute and Clinical Center, Sunnyvale, California.
authors: Grace S Lin
authors: GS
authors: Liang
authors: University of Texas Health Science Center at Houston.
authors: Sheng T
authors: ST
authors: Luo
authors: Johns Hopkins University, Baltimore, Maryland.
authors: Zoltan
authors: Z
authors: Mari
authors: Georgia Regents University, Augusta.
authors: John C
authors: JC
authors: Morgan
authors: Struthers Parkinson's Center, Golden Valley, Minnesota.
authors: Sotirios
authors: S
authors: Parashos
authors: University of Texas Health Science Center at Houston.
authors: Adriana
authors: A
authors: Pérez
authors: Pacific Health Research and Education Institute, Honolulu, Hawaii.
authors: Helen
authors: H
authors: Petrovitch
authors: University of Texas Health Science Center at Houston.
authors: Suja
authors: S
authors: Rajan
authors: University of Pennsylvania, Philadelphia.
authors: Sue
authors: S
authors: Reichwein
authors: University of California, San Francisco.
authors: Jessie Tatsuno
authors: JT
authors: Roth
authors: Thomas Jefferson University, Philadelphia, Pennsylvania.
authors: Jay S
authors: JS
authors: Schneider
authors: Rush University Medical Center, Chicago, Illinois.
authors: Kathleen M
authors: KM
authors: Shannon
authors: Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors: David K
authors: DK
authors: Simon
authors: Northwestern University, Chicago, Illinois.
authors: Tanya
authors: T
authors: Simuni
authors: University of Miami, Miami, Florida.
authors: Carlos
authors: C
authors: Singer
authors: Brigham and Women's Hospital, Boston, Massachusetts.
authors: Lewis
authors: L
authors: Sudarsky
authors: The Parkinson's Institute and Clinical Center, Sunnyvale, California.
authors: Caroline M
authors: CM
authors: Tanner
authors: Brigham and Women's Hospital, Boston, Massachusetts.
authors: Chizoba C
authors: CC
authors: Umeh
authors: Northwestern University, Chicago, Illinois.
authors: Karen
authors: K
authors: Williams
authors: Brigham and Women's Hospital, Boston, Massachusetts.
authors: Anne-Marie
authors: AM
authors: Wills
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003401:Creatine / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D003401:Creatine