title: A randomized sequential trial of creatine in amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is a fatal disease with no cure. In a transgenic mouse model of ALS, creatine monohydrate showed a promising increase in survival. We performed a double-blind, placebo-controlled, sequential clinical trial to assess the effect of creatine monohydrate on survival and disease progression in patients with ALS. Between June 2000 and December 2001, 175 patients with probable, probable-laboratory supported, or definite ALS were randomly assigned to receive either creatine monohydrate or placebo 10 gm daily. A sequential trial design was used with death, persistent assisted ventilation, or tracheostomy as primary end points. Secondary outcome measurements were rate of decline of isometric arm muscle strength, forced vital capacity, functional status, and quality of life. The trial was stopped when the null hypothesis of indifference was accepted. Creatine did not affect survival (cumulative survival probability of 0.70 in the creatine group vs 0.68 in the placebo group at 12 months, and 0.52 in the creatine group vs 0.47 in the placebo group at 16 months), or the rate of decline of functional measurements. Creatine intake did not cause important adverse reactions. This placebo-controlled trial did not find evidence of a beneficial effect of creatine monohydrate on survival or disease progression in patients with ALS.
authors.affiliation: Department of Neurology, University Medical Center Utrecht, The Netherlands.
authors.forename: G J
authors.initials: GJ
authors.lastname: Groeneveld
authors.forename: Jan H
authors.initials: JH
authors.lastname: Veldink
authors.forename: Ingeborg
authors.initials: I
authors.lastname: van der Tweel
authors.forename: Sandra
authors.initials: S
authors.lastname: Kalmijn
authors.forename: Cornelis
authors.initials: C
authors.lastname: Beijer
authors.forename: Marianne
authors.initials: M
authors.lastname: de Visser
authors.forename: John H J
authors.initials: JH
authors.lastname: Wokke
authors.forename: Hessel
authors.initials: H
authors.lastname: Franssen
authors.forename: Leonard H
authors.initials: LH
authors.lastname: van den Berg
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000401:mortality; D003401:Creatine / Q000008:administration & dosage* / Q000009:adverse effects / Q000652:urine; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017211:Treatment Failure
chemical_list: D003401:Creatine