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

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung


  • TUDCA-ALS Study Group - (Autor:in)
  • Italian National Institute of Health
  • University of Rome La Sapienza
  • IRCCS Humanitas Research Hospital
  • Universitätsklinikum Ulm
  • Sheffield Hallam University
  • Centre de Référence Maladie Rare (CRMR) SLA Et Les Autres Maladies du Neurone Moteur (FILSLAN)
  • Universitair Ziekenhuis (UZ) Leuven
  • Universitätsklinikum Utrecht
  • Trinity College Dublin
  • Medical Institute of Ministry of Interior Affairs
  • Motor Neurone Disease Association


BACKGROUND: Amyotrophic 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.

METHODS: The 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 REGISTRATION: ClinicalTrials.gov NCT03800524 . Registered on January 11, 2019.


Seiten (von - bis)792
PublikationsstatusVeröffentlicht - 5 Dez. 2023
Extern publiziertJa

Externe IDs

PubMedCentral PMC10696667
Scopus 85178464967



  • Humans, Amyotrophic Lateral Sclerosis/diagnosis, Riluzole, Neuroprotective Agents/adverse effects, Reproducibility of Results, Double-Blind Method, Treatment Outcome, Disease Progression