title: A clinical trial of creatine in ALS.
abstract: BACKGROUND
  Mitochondrial dysfunction occurs early in the course of ALS, and the mitochondria may be an important site for therapeutic intervention. Creatine stabilizes the mitochondrial transition pore, and is important in mitochondrial ATP production. In a transgenic mouse model of ALS, administration of creatine prolongs survival and preserves motor function and motor neurons.
  
  
  METHODS
  The authors conducted a randomized double-blind, placebo controlled trial on 104 patients with ALS from 14 sites to evaluate the efficacy of creatine supplementation in ALS. The primary outcome measure was maximum voluntary isometric contraction of eight upper extremity muscles, with secondary outcomes including grip strength, ALS Functional Rating Scale-Revised, and motor unit number estimates. Patients were treated for 6 months, and evaluated monthly.
  
  
  RESULTS
  Creatine was tolerated well, but no benefit of creatine could be demonstrated in any outcome measure. CI analysis showed that the study, although powered to detect a 50% or greater change in rate of decline of muscle strength, actually made an effect size of greater than 23% unlikely. It was also demonstrated that motor unit number estimation was performed with acceptable reproducibility and tolerability, and may be a useful outcome measure in future clinical trials.
  
  
  CONCLUSIONS
  Any beneficial effect of creatine at 5 g per day in ALS must be small. Other agents should be considered in future studies of therapeutic agents to address mitochondrial dysfunction in ALS. In addition, motor unit number estimation may be a useful outcome measure for future clinical trials in ALS.
authors.affiliation: Department of Neurology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13104, USA. shefnerj@upstate.edu
authors.forename: J M
authors.initials: JM
authors.lastname: Shefner
authors.forename: M E
authors.initials: ME
authors.lastname: Cudkowicz
authors.forename: D
authors.initials: D
authors.lastname: Schoenfeld
authors.forename: T
authors.initials: T
authors.lastname: Conrad
authors.forename: J
authors.initials: J
authors.lastname: Taft
authors.forename: M
authors.initials: M
authors.lastname: Chilton
authors.forename: L
authors.initials: L
authors.lastname: Urbinelli
authors.forename: M
authors.initials: M
authors.lastname: Qureshi
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: A
authors.initials: A
authors.lastname: Pestronk
authors.forename: J
authors.initials: J
authors.lastname: Caress
authors.forename: P
authors.initials: P
authors.lastname: Donofrio
authors.forename: E
authors.initials: E
authors.lastname: Sorenson
authors.forename: W
authors.initials: W
authors.lastname: Bradley
authors.forename: C
authors.initials: C
authors.lastname: Lomen-Hoerth
authors.forename: E
authors.initials: E
authors.lastname: Pioro
authors.forename: K
authors.initials: K
authors.lastname: Rezania
authors.forename: M
authors.initials: M
authors.lastname: Ross
authors.forename: R
authors.initials: R
authors.lastname: Pascuzzi
authors.forename: T
authors.initials: T
authors.lastname: Heiman-Patterson
authors.forename: R
authors.initials: R
authors.lastname: Tandan
authors.forename: H
authors.initials: H
authors.lastname: Mitsumoto
authors.forename: J
authors.initials: J
authors.lastname: Rothstein
authors.forename: T
authors.initials: T
authors.lastname: Smith-Palmer
authors.forename: D
authors.initials: D
authors.lastname: MacDonald
authors.forename: D
authors.initials: D
authors.lastname: Burke
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis / Q000188:drug therapy* / Q000652:urine; D003401:Creatine / Q000009:adverse effects / Q000627:therapeutic use* / Q000652:urine; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007537:Isometric Contraction; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D003401:Creatine