title: Lithium lacks effect on survival in amyotrophic lateral sclerosis: a phase IIb randomised sequential trial.
abstract: OBJECTIVE
  To determine the safety and efficacy of lithium for the treatment of amyotrophic lateral sclerosis (ALS) in a randomised, placebo controlled, double blind, sequential trial.
  
  
  METHODS
  Between November 2008 and June 2011, 133 patients were randomised to receive lithium carbonate (target blood level 0.4-0.8 mEq/l) or placebo as add-on treatment with riluzole. The primary endpoint was survival, defined as death, tracheostomal ventilation or non-invasive ventilation for more than 16 h/day. Secondary outcome measures consisted of the revised ALS Functional Rating Scale and forced vital capacity. Analysis was by intention to treat and according to a sequential trial design.
  
  
  RESULTS
  61 patients reached a primary endpoint, 33 of 66 in the lithium group and 28 of 67 patients in the placebo group. Lithium did not significantly affect survival (cumulative survival probability of 0.73 in the lithium group (95% CI 0.63 to 0.86) vs 0.75 in the placebo group (95% CI 0.65 to 0.87) at 12 months and 0.62 in the lithium group (95% CI 0.50 to 0.76) vs 0.67 in the placebo group (95% CI 0.56 to 0.81) at 16 months). Secondary outcome measures did not differ between treatment groups. No major safety concerns were encountered.
  
  
  CONCLUSIONS
  This trial, designed to detect a modest effect of lithium, did not demonstrate any beneficial effect on either survival or functional decline in patients with ALS.
  
  
  BACKGROUND
  NTR1448. Name of trial registry: Lithium trial in ALS.
authors.affiliation: Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: Verstraete
authors.forename: Jan H
authors.initials: JH
authors.lastname: Veldink
authors.forename: Mark H B
authors.initials: MH
authors.lastname: Huisman
authors.forename: Tim
authors.initials: T
authors.lastname: Draak
authors.forename: Esther V
authors.initials: EV
authors.lastname: Uijtendaal
authors.forename: Anneke J
authors.initials: AJ
authors.lastname: van der Kooi
authors.forename: H Jurgen
authors.initials: HJ
authors.lastname: Schelhaas
authors.forename: Marianne
authors.initials: M
authors.lastname: de Visser
authors.forename: Ingeborg
authors.initials: I
authors.lastname: van der Tweel
authors.forename: Leonard H
authors.initials: LH
authors.lastname: van den Berg
mesh_terms: D000203:Activities of Daily Living; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood / Q000188:drug therapy* / Q000401:mortality*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006801:Humans; D016651:Lithium Carbonate / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012123:Pulmonary Ventilation / Q000187:drug effects; D019782:Riluzole / Q000627:therapeutic use; D015996:Survival Rate; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D016651:Lithium Carbonate; D019782:Riluzole