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.
Amyotrophic lateral sclerosis
Bile acids
Clinical trial
Double-blind
Phase III
Randomized
Statistical analysis plan
Journal
Trials
ISSN: 1745-6215
Titre abrégé: Trials
Pays: England
ID NLM: 101263253
Informations de publication
Date de publication:
05 Dec 2023
05 Dec 2023
Historique:
received:
23
07
2023
accepted:
22
08
2023
medline:
7
12
2023
pubmed:
6
12
2023
entrez:
5
12
2023
Statut:
epublish
Résumé
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. 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. 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. ClinicalTrials.gov NCT03800524 . Registered on January 11, 2019.
Sections du résumé
BACKGROUND
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
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
CONCLUSIONS
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
BACKGROUND
ClinicalTrials.gov NCT03800524 . Registered on January 11, 2019.
Identifiants
pubmed: 38053196
doi: 10.1186/s13063-023-07638-w
pii: 10.1186/s13063-023-07638-w
pmc: PMC10696667
doi:
Substances chimiques
Riluzole
7LJ087RS6F
ursodoxicoltaurine
60EUX8MN5X
Neuroprotective Agents
0
Banques de données
ClinicalTrials.gov
['NCT03800524']
Types de publication
Randomized Controlled Trial
Multicenter Study
Clinical Trial, Phase III
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
792Subventions
Organisme : Horizon 2020 Framework Programme
ID : 755094
Investigateurs
Paolo Tornese
(P)
Antoniangela Cocco
(A)
Michela Matteoli
(M)
Eliana Lauranzano
(E)
Maria Luisa Malosio
(ML)
Chiara Adriana Elia
(CA)
Adriano Chiò
(A)
Umberto Manera
(U)
Cristina Moglia
(C)
Andrea Calvo
(A)
Paolina Salamone
(P)
Giuseppe Fuda
(G)
Carlo Colosimo
(C)
Cristina Spera
(C)
Prabha Cristina Ranchicchio
(PC)
Giuseppe Stipa
(G)
Domenico Frondizi
(D)
Christian Lunetta
(C)
Valeria Sansone
(V)
Claudia Tarlarini
(C)
Francesca Gerardi
(F)
Vincenzo Silani
(V)
Alberto Doretti
(A)
Eleonora Colombo
(E)
Gianluca Demirtzidis
(G)
Gioacchino Tedeschi
(G)
Francesca Trojsi
(F)
Carla Passaniti
(C)
Stefania Ballestrero
(S)
Johannes Dorst
(J)
Ulrike Weiland
(U)
Andrea Fromm
(A)
Maximilian Wiesenfarth
(M)
Katharina Kandler
(K)
Simon Witzel
(S)
Markus Otto
(M)
Joachim Schuster
(J)
Thomas Meyer
(T)
André Maier
(A)
Dagmar Kettemann
(D)
Susanne Petri
(S)
Lars Müschen
(L)
Camilla Wohnrade
(C)
Anastasia Sarikidi
(A)
Alma Osmanovic
(A)
Julian Grosskreutz
(J)
Annekathrin Rödiger
(A)
Robert Steinbach
(R)
Benjamin Ilse
(B)
Uta Smesny
(U)
Robert Untucht
(R)
René Günther
(R)
Maximilian Vidovic
(M)
Pamela Shaw
(P)
Alexis Collins
(A)
Helen Wollff
(H)
Theresa Walsh
(T)
Lee Tuddenham
(L)
Mbombe Kazoka
(M)
David White
(D)
Stacy Young
(S)
Benjamin Thompson
(B)
Daniel Madarshahian
(D)
Suresh K Chhetri
(SK)
Amina Chaouch
(A)
Carolyn A Young
(CA)
Heike Arndt
(H)
Coliver Hanemann
(C)
Thomas Lambert
(T)
Stephane Beltran
(S)
Philippe Couratier
(P)
Florence Esselin
(F)
William Camu
(W)
Elisa De La Cruz
(E)
Gwendal Lemasson
(G)
Pegah Masrori
(P)
Sinead Maguire
(S)
Liz Fogarty
(L)
Toyosi Atoyebi
(T)
Niamh Ní Obáin
(NN)
Informations de copyright
© 2023. The Author(s).
Références
Front Neurol. 2022 Sep 27;13:1009113
pubmed: 36237618
Amyotroph Lateral Scler. 2012 Feb;13(2):210-6
pubmed: 22292842
Amyotroph Lateral Scler Frontotemporal Degener. 2013 Sep;14(5-6):346-52
pubmed: 23621426
Stat Biopharm Res. 2020 Jul 6;12(4):399-411
pubmed: 34191971
Amyotroph Lateral Scler. 2010;11(1-2):178-80
pubmed: 19634063
Muscle Nerve. 2021 Oct;64(4):E18-E20
pubmed: 34255865
J Neurol Neurosurg Psychiatry. 2020 Jan;91(1):75-81
pubmed: 31558653
Stat Biopharm Res. 2020 Jul 14;12(4):427-437
pubmed: 34191975
Med Res Rev. 2019 Mar;39(2):733-748
pubmed: 30101496
Ann Neurol. 2009 Aug;66(2):235-44
pubmed: 19743457
Lancet. 2020 Aug 22;396(10250):523-524
pubmed: 32828180
Trials. 2022 Apr 18;23(1):328
pubmed: 35436970
N Engl J Med. 2005 Aug 4;353(5):487-97
pubmed: 16079372
BMC Health Serv Res. 2016 Jul 08;16:236
pubmed: 27391223
J Clin Neuromuscul Dis. 2021 Mar 1;22(3):180-181
pubmed: 33596004
Neurology. 2006 Oct 10;67(7):1294-6
pubmed: 17030772
Eur J Neurol. 2016 Jan;23(1):45-52
pubmed: 25664595
BMC Med Res Methodol. 2019 Jul 23;19(1):161
pubmed: 31345166
Amyotroph Lateral Scler Frontotemporal Degener. 2021 Nov;22(7-8):505-507
pubmed: 33576710
Clin Epidemiol. 2018 Mar 19;10:333-341
pubmed: 29593436
Transl Neurodegener. 2022 Jun 4;11(1):33
pubmed: 35659112
Brain. 2023 Jul 3;146(7):2711-2716
pubmed: 36310538
Amyotroph Lateral Scler Other Motor Neuron Disord. 2000 Dec;1(5):293-9
pubmed: 11464847
Neuroepidemiology. 2013;41(2):118-30
pubmed: 23860588
BMC Med Res Methodol. 2020 Aug 12;20(1):208
pubmed: 32787782
Pharm Stat. 2018 May;17(3):202-213
pubmed: 29282880
J Neurol Neurosurg Psychiatry. 2022 May;93(5):521-529
pubmed: 35228271
Biometrics. 2000 Sep;56(3):779-88
pubmed: 10985216
JAMA. 2017 Dec 19;318(23):2337-2343
pubmed: 29260229
Life (Basel). 2023 Jan 11;13(1):
pubmed: 36676159
Brain Sci. 2021 Sep 29;11(10):
pubmed: 34679356