Lithium lacks effect on survival in amyotrophic lateral sclerosis: a phase IIb randomised sequential trial. Issue 5 (29th February 2012)

• Record Type: Journal Article
• Authors: Verstraete, Esther; Veldink, Jan H; Huisman, Mark H B; Draak, Tim; Uijtendaal, Esther V; van der Kooi, Anneke J; Schelhaas, H Jurgen; de Visser, Marianne; van der Tweel, Ingeborg; van den Berg, Leonard H
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 83:Issue 5(2012)
• Page Start: 557
• Page End: 564
• Publication Date: 2012-02-29
• Subjects: Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp-2011-302021
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : 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.