Lithium lacks effect on survival in amyotrophic lateral sclerosis: a phase IIb randomised sequential trial
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.
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Despite early enthusiasm over lithium in patients and mouse models, five subsequent trials showed no clinical benefit in survival or neuromuscular outcomes for ALS patients.
“Despite early enthusiasm over lithium in patients and mouse models [505,506], five subsequent trials showed no clinical benefit in survival or neuromuscular outcomes for ALS patients [507–511].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [511]
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- Authors
- Verstraete, E., Veldink, J. H., Huisman, M. H. B., Draak, T., Uijtendaal, E. V., van der Kooi, A. J., Schelhaas, H. J., de Visser, M., van der Tweel, I., & van den Berg, L. H.
- Affiliations
- University Medical Center Utrecht (NL)
- Radboud University Nijmegen (NL)
- Venue
- Journal of Neurology, Neurosurgery & Psychiatry
- Publisher
- BMJ
- Published
- 2012-02-29
- Volume
- 83
- Issue
- 5
- Pages
- 557-564
- ISSN
- 0022-3050 (ISSN-L)
- 1468-330X
- OpenAlex
- W2142460456
- Cited by
- 78
- References
- 32
- Citations by year
- 2026: 1 · 2023: 4 · 2022: 3 · 2021: 7 · 2020: 10 · 2019: 4 · 2018: 4 · 2017: 5 · 2016: 4 · 2015: 9 · 2014: 11 · 2013: 12 · 2012: 3
- FWCI
- 7.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurology Neurosurgery & Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Radboud Universiteit
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Amyloidosis: Diagnosis, Treatment, Outcomes
- Keywords
- amyotrophic lateral sclerosis, lithium carbonate, riluzole, survival, functional decline, forced vital capacity, ALS Functional Rating Scale, adjunctive therapy, drug safety
- MeSH terms
- Activities of Daily Living, Adolescent, Adult, Aged, Aged, 80 and over, Amyotrophic Lateral Sclerosis, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Pulmonary Ventilation, Vital Capacity, Survival Rate, Lithium Carbonate, Riluzole
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