Evidence map›Paper›PMID 36471413›Full record

ArticleTrials2022

Lithium carbonate in amyotrophic lateral sclerosis patients homozygous for the C-allele at SNP rs12608932 in UNC13A: protocol for a confirmatory, randomized, group-sequential, event-driven, double-blind, placebo-controlled trial.

Sean W Willemse, Kit C B Roes, Philip Van Damme, Orla Hardiman, Caroline Ingre, Monica Povedano, Naomi R Wray, Marleen Gijzen, Mirjam S de Pagter, Koen C Demaegd and 11 more

Open access · goldAbstract readClinical Trial Protocol
PubMed Full text at PMC Publisher
In one paragraph

Article in Trials, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
2.5field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.

  1. Safety and efficacy of lithium in patients with amyotrophic lateral sclerosis: a systematic review and meta-analysis of randomized controlled trials.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2023
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  10. Journal of neurology, neurosurgery, and psychiatry · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors at 12 institutions in 9 countries.

Sean W WillemseDepartment of Neurology, UMC Utrecht, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0002-0198-5740
Kit C B RoesDepartment of Health Evidence, Radboud UMC, Nijmegen, The Netherlands.
Philip Van DammeDepartment of Neurology, University Hospitals Leuven, Leuven, Belgium.
Orla HardimanDepartment of Neurology, National Neuroscience Centre, Beaumont Hospital, Dublin, Ireland.
Caroline IngreDepartment of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
Monica PovedanoFunctional Unit of Amyotrophic Lateral Sclerosis (UFELA), Service of Neurology, Bellvitge University Hospital, Hospitalet de Llobregat, Spain.
Naomi R WrayInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
Marleen GijzenDepartment of Genetics, UMC Utrecht, Utrecht, The Netherlands.
Mirjam S de PagterDepartment of Genetics, UMC Utrecht, Utrecht, The Netherlands.
Koen C DemaegdDepartment of Neurology, UMC Utrecht, Utrecht, The Netherlands.
Annemarie F C JanseTRICALS, Utrecht, The Netherlands.
Roel G VinkTRICALS, Utrecht, The Netherlands.
Boudewijn T H M SleutjesDepartment of Neurology, UMC Utrecht, Utrecht, The Netherlands.
Adriano Chiò'Rita Levi Montalcini' Department of Neuroscience, University of Turin, Turin, Italy.
Philippe CorciaCentre Constitutif SLA, CHRU de Tours - Fédération des centres SLA Tours-Limoges, LitORALS, Tours, France.
Evy ReviersEuropean Organization for Professionals and Patients with ALS (EUpALS) & ALS Liga Belgium, Leuven, Belgium.
Ammar Al-ChalabiDepartment of Basic and Clinical Neuroscience, King's College London, Maurice Wohl Clinical Neuroscience Institute, London, UK.
Matthew C KiernanDepartment of Neurology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
Leonard H van den BergDepartment of Neurology, UMC Utrecht, Utrecht, The Netherlands.
Michael A van EsDepartment of Neurology, UMC Utrecht, Utrecht, The Netherlands.
Ruben P A van EijkDepartment of Neurology, UMC Utrecht, Utrecht, The Netherlands. R.P.A.vanEijk-2@umcutrecht.nl.
Utrecht University · NLUniversity Medical Center Utrecht · NLAzienda Ospedaliera Citta' della Salute e della Scienza di Torino · ITBellvitge University Hospital · ESCentre Hospitalier Universitaire de Tours · FRKarolinska Institutet · SEKing's College London · GBKU Leuven · BERadboud University Nijmegen · NLRoyal College of Surgeons in Ireland · IEThe University of Queensland · AUThe University of Sydney · AU

Funding

Fonds Wetenschappelijk Onderzoek T003519NMedical Research Council MR/R024804/1Motor Neurone Disease Association ALCHALABI-DOBSON/APR14/829-791
6 · The paper itself

Abstract

backgroundGiven the large genetic heterogeneity in amyotrophic lateral sclerosis (ALS), it seems likely that genetic subgroups may benefit differently from treatment. An exploratory meta-analysis identified that patients homozygous for the C-allele at SNP rs12608932, a single nucleotide polymorphism in the gene UNC13A, had a statistically significant survival benefit when treated with lithium carbonate. We aim to confirm the efficacy of lithium carbonate on the time to death or respiratory insufficiency in patients with ALS homozygous for the C-allele at SNP rs12608932 in UNC13A.

methodsA randomized, group-sequential, event-driven, double-blind, placebo-controlled trial will be conducted in 15 sites across Europe and Australia. Patients will be genotyped for UNC13A; those homozygous for the C-allele at SNP rs12608932 will be eligible. Patients must have a diagnosis of ALS according to the revised El Escorial criteria, and a TRICALS risk-profile score between -6.0 and -2.0. An expected number of 1200 patients will be screened in order to enroll a target sample size of 171 patients. Patients will be randomly allocated in a 2:1 ratio to lithium carbonate or matching placebo, and treated for a maximum duration of 24 months. The primary endpoint is the time to death or respiratory insufficiency, whichever occurs first. Key secondary endpoints include functional decline, respiratory function, quality of life, tolerability, and safety. An interim analysis for futility and efficacy will be conducted after the occurrence of 41 events. DISCUSSION: Lithium carbonate has been proven to be safe and well-tolerated in patients with ALS. Given the favorable safety profile, the potential benefits are considered to outweigh the burden and risks associated with study participation. This study may provide conclusive evidence about the life-prolonging potential of lithium carbonate in a genetic ALS subgroup.

trial registrationEudraCT number 2020-000579-19 . Registered on 29 March 2021.

Indexed as

Amyotrophic Lateral SclerosisRespiratory InsufficiencyAllelesHumansLithium CarbonateMeta-Analysis as TopicPolymorphism, Single NucleotideQuality of LifeRandomized Controlled Trials as TopicLithium CarbonateAmyotrophic lateral sclerosisLithium carbonateRandomized controlled trialSNP rs12608932UNC13A

Identifiers

PMID36471413
PMCPMC9721045
OpenAlexW4310679691

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.