Objectives 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.
Trial registration number NTR1448. Name of trial registry: Lithium trial in ALS.
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Funding The authors are grateful for funding of this study from the ‘Zeldzame Ziekten Fonds’, The Zabawas Foundation, The Netherlands ALS Foundation, Optimix Foundation and Jan Cornelia Foundation.
Competing interests None.
Ethics approval The study was approved by the Medical Ethics Committee for Research into Humans of the University Medical Centre Utrecht (and received local approval from the Medical Ethics Committee for Research into Humans of the Academic Medical Centre, Amsterdam and Radboud University Medical Centre, Nijmegen).
Provenance and peer review Not commissioned; externally peer reviewed.