Evidence map›Paper›PMID 38053196›Full record

Trial reportTrials2023

A randomized double-blind clinical trial on safety and efficacy of tauroursodeoxycholic acid (TUDCA) as add-on treatment in patients affected by amyotrophic lateral sclerosis (ALS): the statistical analysis plan of TUDCA-ALS trial.

Flavia L Lombardo, Stefania Spila Alegiani, Flavia Mayer, Marta Cipriani, Maria Lo Giudice, Albert Christian Ludolph, Christopher J McDermott, Philippe Corcia, Philip Van Damme, Leonard H Van den Berg and 7 more

Registry-linked trialOpen access · goldAbstract readRandomized Controlled TrialMulticenter StudyClinical Trial, Phase III
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Trials, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03800524 (Safety and Efficacy of Tauroursodeoxycholic), which is not on this map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
2.5field-weighted citation impact, top 10% 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.

NCT03800524 phase3unknown statusnot on this map

Safety and Efficacy of Tauroursodeoxycholic (TUDCA) as add-on Treatment in Patients Affected by Amyotrophic Lateral Sclerosis (ALS)

TypeinterventionalSponsorHumanitas Mirasole SpARan2019 to 2023Enrolled337ConditionsAmyotrophic Lateral Sclerosis (ALS)ArmsTauroursodeoxycholic Acid, Placebo
3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Emerging Roles of Bile Acids in Neuroinflammation.International journal of molecular sciences · 2025
    Review
  5. Article
  6. Review
  7. Review
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

17 authors at 11 institutions in 8 countries.

Flavia L Lombardo *National Centre for Disease Prevention and Health Promotion, Italian National Institute of Health, Rome, Italy. flavia.lombardo@iss.it.ORCID http://orcid.org/0000-0001-6183-0735
Stefania Spila Alegiani *National Center for Drug Research and Evaluation, Italian National Institute of Health, Rome, Italy.
Flavia MayerNational Center for Drug Research and Evaluation, Italian National Institute of Health, Rome, Italy.
Marta CiprianiDepartment of Statistical Sciences, Sapienza University of Rome, Rome, Italy.
Maria Lo GiudiceNeurology Department, IRCCS Humanitas Research Hospital, Rozzano, Italy.
Albert Christian LudolphNeurology Department, University of Ulm, Ulm, Germany.
Christopher J McDermottDepartment of Neuroscience, Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK.
Philippe CorciaCentre de Référence Maladie Rare (CRMR) SLA Et Les Autres Maladies du Neurone Moteur (FILSLAN), Tours, France.
Philip Van DammeNeurology Department, University Hospitals Leuven, Louvain, Belgium.
Leonard H Van den BergDepartment of Neurology, UMC Utrecht Brain Center, University Medical Centre Utrecht, Utrecht, Netherlands.
Orla HardimanAcademic Unit of Neurology, Trinity Biomedical Sciences Institute, Dublin, Ireland.
Gabriele NicoliniMedical Affairs, Bruschettini S.R.L, Genoa, Italy.
Nicola VanacoreNational Centre for Disease Prevention and Health Promotion, Italian National Institute of Health, Rome, Italy.
Brian DickieMotor Neurone Disease Association, Northampton, UK.
Alberto AlbaneseNeurology Department, IRCCS Humanitas Research Hospital, Rozzano, Italy.
Maria PuopoloDepartment of Neuroscience, Italian National Institute of Health, Rome, Italy.
TUDCA-ALS Study Group
IRCCS Humanitas Research Hospital · ITIstituto Superiore di Sanità · ITUniversität Ulm · DEUniversité de Tours · FRBruschettini (Italy) · ITKU Leuven · BEMotor Neurone Disease Association · GBSapienza University of Rome · ITTrinity College Dublin · IEUniversity Medical Center Utrecht · NLUniversity of Sheffield · GB

Funding

Horizon 2020 Framework Programme 755094
6 · The paper itself

Abstract

backgroundAmyotrophic lateral sclerosis (ALS) is a highly debilitating neurodegenerative condition. Despite recent advancements in understanding the molecular mechanisms underlying ALS, there have been no significant improvements in therapeutic options for ALS patients in recent years. Currently, there is no cure for ALS, and the only approved treatment in Europe is riluzole, which has been shown to slow the disease progression and prolong survival by approximately 3 months. Recently, tauroursodeoxycholic acid (TUDCA) has emerged as a promising and effective treatment for neurodegenerative diseases due to its neuroprotective activities.

methodsThe ongoing TUDCA-ALS study is a double-blinded, parallel arms, placebo-controlled, randomized multicenter phase III trial with the aim to assess the efficacy and safety of TUDCA as add-on therapy to riluzole in patients with ALS. The primary outcome measure is the treatment response defined as a minimum of 20% improvement in the ALS Functional Rating Scale-Revised (ALSFRS-R) slope during the randomized treatment period (18 months) compared to the lead-in period (3 months). Randomization will be stratified by country. Primary analysis will be conducted based on the intention-to-treat principle through an unadjusted logistic regression model. Patient recruitment commenced on February 22, 2019, and was closed on December 23, 2021. The database will be locked in September 2023. DISCUSSION: This paper provides a comprehensive description of the statistical analysis plan in order to ensure the reproducibility of the analysis and avoid selective reporting of outcomes and data-driven analysis. Sensitivity analyses have been included in the protocol to assess the impact of intercurrent events related to the coronavirus disease 2019. By focusing on clinically meaningful and robust outcomes, this trial aims to determine whether TUDCA can be effective in slowing the disease progression in patients with ALS.

trial registrationClinicalTrials.gov NCT03800524 . Registered on January 11, 2019.

Indexed as

Amyotrophic Lateral SclerosisNeuroprotective AgentsDisease ProgressionDouble-Blind MethodHumansReproducibility of ResultsRiluzoleTaurochenodeoxycholic AcidTreatment OutcomeNeuroprotective AgentsRiluzoleTaurochenodeoxycholic AcidursodoxicoltaurineAmyotrophic lateral sclerosisBile acidsClinical trialDouble-blindPhase IIIRandomizedStatistical analysis plan

Identifiers

PMID38053196
PMCPMC10696667
OpenAlexW4389348100

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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.