title: Phase II screening trial of lithium carbonate in amyotrophic lateral sclerosis: examining a more efficient trial design.
abstract: OBJECTIVE
  To use a historical placebo control design to determine whether lithium carbonate slows progression of amyotrophic lateral sclerosis (ALS).
  
  
  METHODS
  A phase II trial was conducted at 10 sites in the Western ALS Study Group using similar dosages (300-450 mg/day), target blood levels (0.3-0.8 mEq/L), outcome measures, and trial duration (13 months) as the positive trial. However, taking riluzole was not a requirement for study entry. Placebo outcomes in patients matched for baseline features from a large database of recent clinical trials, showing stable rates of decline over the past 9 years, were used as historical controls.
  
  
  RESULTS
  The mean rate of decline of the ALS Functional Rating Scale-Revised was greater in 107 patients taking lithium carbonate (-1.20/month, 95% confidence interval [CI] -1.41 to -0.98) than that in 249 control patients (-1.01/month, 95% CI -1.11 to -0.92, p = 0.04). There were no differences in secondary outcome measures (forced vital capacity, time to failure, and quality of life), but there were more adverse events in the treated group.
  
  
  CONCLUSIONS
  The lack of therapeutic benefit and safety concerns, taken together with similar results from 2 other recent trials, weighs against the use of lithium carbonate in patients with ALS. The absence of drift over time and the availability of a large database of patients for selecting a matched historical control group suggest that use of historical controls may result in more efficient phase II trials for screening putative ALS therapeutic agents.
  
  
  METHODS
  This study provided Class IV evidence that lithium carbonate does not slow the rate of decline of function in patients with ALS over 13 months.
authors.affiliation: California Pacific Medical Center, San Francisco, CA, USA. millerrx@sutterhealth.org
authors.forename: R G
authors.initials: RG
authors.lastname: Miller
authors.forename: D H
authors.initials: DH
authors.lastname: Moore
authors.forename: D A
authors.initials: DA
authors.lastname: Forshew
authors.forename: J S
authors.initials: JS
authors.lastname: Katz
authors.forename: R J
authors.initials: RJ
authors.lastname: Barohn
authors.forename: M
authors.initials: M
authors.lastname: Valan
authors.forename: M B
authors.initials: MB
authors.lastname: Bromberg
authors.forename: K L
authors.initials: KL
authors.lastname: Goslin
authors.forename: M C
authors.initials: MC
authors.lastname: Graves
authors.forename: L F
authors.initials: LF
authors.lastname: McCluskey
authors.forename: A L
authors.initials: AL
authors.lastname: McVey
authors.forename: T
authors.initials: T
authors.lastname: Mozaffar
authors.forename: J M
authors.initials: JM
authors.lastname: Florence
authors.forename: A
authors.initials: A
authors.lastname: Pestronk
authors.forename: M
authors.initials: M
authors.lastname: Ross
authors.forename: E P
authors.initials: EP
authors.lastname: Simpson
authors.forename: S H
authors.initials: SH
authors.lastname: Appel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D016651:Lithium Carbonate / Q000627:therapeutic use*; D008297:Male; D008403:Mass Screening / Q000639:trends; D008875:Middle Aged; D012107:Research Design / Q000639:trends; D055815:Young Adult
chemical_list: D016651:Lithium Carbonate