BACKGROUND: Amyotrophic lateral sclerosis is a rapidly progressive 
neurodegenerative disorder characterised by loss of motor neurons leading to 
severe weakness and death from respiratory failure within 3-5 years. Riluzole 
prolongs survival in ALS. A published report has suggested a dramatic effect of 
lithium carbonate on survival. 44 patients were studied, with 16 randomly 
selected to take LiCO3 and riluzole and 28 allocated to take riluzole alone. In 
the group treated with lithium, no patients had died (i.e., 100% survival) at 
the end of the study (15 months from entry), compared to 71% surviving in the 
riluzole-only group. Although the trial can be criticised on several grounds, 
there is a substantial rationale from other laboratory studies that lithium is 
worth investigating therapeutically in amyotrophic lateral sclerosis.
METHODS/DESIGN: LiCALS is a multi-centre double-blind randomised parallel group 
controlled trial of the efficacy, safety, and tolerability of lithium carbonate 
(LiCO3) at doses to achieve stable 'therapeutic' plasma levels (0.4-0.8 mmol/L), 
plus standard treatment, versus matched placebo plus standard treatment, in 
patients with amyotrophic lateral sclerosis. The study will be based in the UK, 
in partnership with the MND Association and DeNDRoN (the Dementias and 
Neurodegnerative Diseases Clinical Research Network). 220 patients will be 
recruited. All patients will be on the standard treatment for ALS of riluzole 
100 mg daily. The primary outcome measure will be death from any cause at 18 
months defined from the date of randomisation. Secondary outcome measures will 
be changes in three functional rating scales, the ALS Functional Rating 
Scale-Revised, The EuroQOL (EQ-5D), and the Hospital Anxiety and Depression 
Scale.Eligible patients will have El Escorial Possible, Laboratory-supported 
Probable, Probable or Definite amyotrophic lateral sclerosis with disease 
duration between 6 months and 36 months (inclusive), vital capacity ≥ 60% of 
predicted within 1 month prior to randomisation and age at least18 years.
DISCUSSION: Patient recruitment began in June 2009 and the last patient is 
expected to complete the trial protocol in November 2011.
TRIAL REGISTRATION: Current controlled trials ISRCTN83178718.