title: Bromocriptine Mesylate Attenuates Amyotrophic Lateral Sclerosis: A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Research in Japanese Patients.
abstract: OBJECTIVE
  Bromocriptine mesylate (BRC), a dopamine D2 receptor agonist has been shown to confer neuroprotection, sustained motor function and slowed disease progression in mouse models of amyotrophic lateral sclerosis (ALS) Here we report a first in human trial in ALS.
  
  
  METHODS
  A multicenter, Riluzole add-on, randomized, double-blind, placebo controlled 102-week extension BRC clinical trial.
  
  
  METHODS
  The trial was conducted between January 2009 and March 2012 on 36 Japanese ALS patients. A 12-week treatment with Riluzole observational period was followed by combined treatment (Riluzole + BRC; n = 29 or Riluzole + placebo; n = 7). The dosing commenced at 1.25 mg/day increasing in steps at two weeks intervals to a maximum of 15 mg/day. The efficacy of BRC was evaluated by comparing BRC and placebo groups upon completion of stepwise dosing at 14 weeks 2 points (1st endpoint) and upon completion or discontinuation of the study (2nd endpoint) of the dosing.
  
  
  RESULTS
  Statistics analyses revealed a marginal BRC treatment efficacy with P≦20%to placebo by 1st and 2nd endpoint analysis. In the 1st endpoint analysis, BRC group was significantly effective on the scores of ALSAQ40-communicaton (P = 1.2%), eating and drinking (P = 2.2%), ALSFRS-R total (P = 17.6%), grip strength (P = 19.8%) compared to the placebo group. In the 2nd endpoint analysis, differences between the scores of Limb Norris Scale (P = 18.3%), ALSAQ40-communication (P = 11.9%), eating and drinking (P = 13.6%), and neck forward-bent test (P = 15.4%) of BRC group were detected between the two groups. There was no significant difference between the treatment groups for adverse events or serious drug reactions incidence.
  
  
  CONCLUSIONS
  BRC sustains motoneuronal function at least in part through BRC treatment. Further analysis involving a Phase 2b or 3 clinical trial is required but BRC currently shows promise for ALS treatment.
  
  
  BACKGROUND
  UMIN Clinical Trials UMIN000008527.
authors.affiliation: Department of Neurology, Tokai University School of Medicine, Isehara, Japan.
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Nagata
authors.affiliation: Department of Neurology, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Mieko
authors.initials: M
authors.lastname: Ogino
authors.affiliation: Department of Neurology, Toho University Omori Medical Center, Tokyo, Japan.
authors.forename: Kounosuke
authors.initials: K
authors.lastname: Iwamoto
authors.affiliation: Department of Neurology, Tokai University Hachioji Hospital, Tokyo, Japan.
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Kitagawa
authors.affiliation: Department of Neurology, Toho University Omori Medical Center, Tokyo, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Iwasaki
authors.affiliation: Department of Neurology, Tokai University Oiso Hospital, Kanagawa, Japan.
authors.forename: Fumihito
authors.initials: F
authors.lastname: Yoshii
authors.affiliation: Molecular Neurology, Faculty of Medicine, Kitasato University School of Medicine, Sagamihara, Japan.|Department of Pediatrics, Faculty of Medicine, University of Ottawa, ARC/Children's Hospital of Eastern Ontario, Ottawa, Canada.
authors.forename: Joh-E
authors.initials: JE
authors.lastname: Ikeda
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy*; D001971:Bromocriptine / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D019782:Riluzole / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D001971:Bromocriptine; D019782:Riluzole