No evidence of benefit of Lithium on survival in patients with amyotrophic lateral sclerosis
Lithium has neuroprotective effects in cell and animal models of amyotrophic lateral sclerosis ( ALS ), and a small pilot study in patients with ALS showed a significant effect of Lithium on survival.
A study has evaluated whether Lithium improves survival in patients with amyotrophic lateral sclerosis.
The Lithium Carbonate in Amyotrophic Lateral Sclerosis ( LiCALS ) trial is a randomised, double-blind, placebo-controlled trial of oral Lithium taken daily for 18 months in patients with ALS.
Patients aged at least 18 years who had amyotrophic lateral sclerosis according to the revised El Escorial criteria, had disease duration between 6 and 36 months, and were taking Riluzole were recruited from ten centres in the UK.
Patients were randomly assigned ( 1:1 ) to receive either Lithium or matched placebo tablets. Randomisation was via an online system done at the level of the individual by block randomisation with randomly varying block sizes, stratified by study centre and site of disease onset ( limb or bulbar ).
All patients and assessing study personnel were masked to treatment assignment.
The primary endpoint was the rate of survival at 18 months and was analysed by intention to treat.
During the period 2009-2011, 243 patients were screened, 214 of whom were randomly assigned to receive Lithium ( n=107 ) or placebo ( n=107 ).
Two patients discontinued treatment and one died before the target therapeutic Lithium concentration could be achieved. 63 ( 59% ) of 107 patients in the placebo group and 54 ( 50% ) of 107 patients in the Lithium group were alive at 18 months.
The survival functions did not differ significantly between groups ( p=0.20 ).
After adjusting for study Centre and site of onset using logistic regression, the relative odds of survival at 18 months ( Lithium vs placebo ) was 0.71.
Fifty-six patients in the placebo group and 61 in the Lithium group had at least one serious adverse event.
The study found no evidence of benefit of Lithium on survival in patients with amyotrophic lateral sclerosis, but nor were there safety concerns, which had been identified in previous studies with less conventional designs. ( Xagena )
UKMND-LiCALS Study Group, The Lancet Neurology 2013; 12: 339-345