NCT03800524

Brief Summary

This is a Phase III, multi-centre, randomized, double-blind, placebo-controlled, parallel-group study to evaluate Safety and Efficacy of Tauroursodeoxycholic (TUDCA) as add-on Treatment in Patients Affected by Amyotrophic Lateral Sclerosis (ALS).

Trial Health

50
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
337

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Feb 2019

Longer than P75 for phase_3

Geographic Reach
7 countries

25 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 4, 2019

Completed
7 days until next milestone

First Posted

Study publicly available on registry

January 11, 2019

Completed
1 month until next milestone

Study Start

First participant enrolled

February 22, 2019

Completed
4.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2023

Completed
Last Updated

July 10, 2023

Status Verified

July 1, 2023

Enrollment Period

4.9 years

First QC Date

January 4, 2019

Last Update Submit

July 7, 2023

Conditions

Amyotrophic Lateral Sclerosis (ALS)

Outcome Measures

Primary Outcomes (1)

  • Number of responder patients

    Identification of the responder patients defined as those showing an improvement of at least 20% in the ALSFRS-R slope

    18 months

Secondary Outcomes (9)

  • Survival time

    18 months

  • ALS disease functional rating scale - revised version (ALSFRS-R)

    18 months

  • ALS Assessment Questionnaire-40 (ALSAQ-40)

    18 months

  • Forced Vital Capacity

    18 months

  • EuroQol 5-Dimension-5 Levels (EQ-5D-5L) scale

    18 months

  • +4 more secondary outcomes

Study Arms (2)

Tauroursodeoxycholic acid (TUDCA)

EXPERIMENTAL

* Tauroursodeoxycholic acid (TUDCA) 250 mg capsules * Doses: 4 capsules (1 g) twice daily 10-15 minutes after a meal * Mode of administration: orally * Duration: 18 months

Drug: Tauroursodeoxycholic Acid

Reference therapy

PLACEBO COMPARATOR

* Placebo capsules identical to active compound * Doses: 4 capsules (1 g) twice daily 10-15 minutes after a meal * Mode of administration: orally * Duration: 18 months

Drug: Placebo

Interventions

Tauroursodeoxycholic AcidDRUG

* Tauroursodeoxycholic acid (TUDCA) 250 mg capsules * Doses: 4 capsules (1 g) twice daily 10-15 minutes after a meal * Mode of administration: orally * Duration: 18 months

Also known as: TUDCA, Tudcabil, Taurolite
Tauroursodeoxycholic acid (TUDCA)
PlaceboDRUG

* Placebo 250 mg capsules * Doses: 4 capsules (1 g) twice daily 10-15 minutes after a meal * Mode of administration: orally * Duration: 18 months

Reference therapy

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Probable laboratory-supported, probable, or definite ALS, as defined by El Escorial Revised ALS diagnostic criteria at screening visit (month -3)
  • Disease duration ≤ 18 months at screening visit (month -3)
  • Able to perform reproducible pulmonary function tests at screening visit (month -3)
  • Forced vital capacity or slow vital capacity ≥70% of normal at screening visit (month -3)
  • Stable on riluzole treatment for 3 months in the lead-in period
  • Signed informed consent at screening visit (month -3)

You may not qualify if:

  • Treatment with edaravone
  • Other causes of neuromuscular weakness
  • Presence of other neurodegenerative diseases
  • Significant cognitive impairment, clinical dementia or psychiatric illness
  • Severe cardiac or pulmonary disease
  • Other diseases precluding functional assessments
  • Other life-threatening diseases
  • Any use of non-invasive ventilation (e.g. continuous positive airway pressure, non-invasive bi-level positive airway pressure or non-invasive volume ventilation) for any portion of the day, or mechanical ventilation via tracheostomy, or on any form of oxygen supplementation
  • Gastrointestinal disorder that is likely to impair absorption of study drug from the gastrointestinal tract
  • Has taken any investigational study drug within 30 days or five half-lives of the prior agent, whichever is longer, prior to dosing
  • Any clinically significant laboratory abnormality
  • Other concurrent investigational medications
  • Active peptic ulcer
  • Previous surgery or infections of small intestine
  • Patients unable to easily swallow the treatment pills
  • +10 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (25)

Katholieke Universiteit Leuven

Leuven, Belgium

Location

Centre Hospitalier Universitaire de Bordeaux

Bordeaux, France

Location

Centre Hospitalier Universitaire Limoges

Limoges, France

Location

Centre Hospitalier Universitaire de Montpellier

Montpellier, France

Location

Centre Hospitalier Regional Universitaire de Tours

Tours, France

Location

Charité - Universitätsmedizin Berlin

Berlin, Germany

Location

Universitätsklinikum Carl Gustav Carus Dresden

Dresden, Germany

Location

Alfried Krupp Krankenhaus Rüttenscheid

Essen, Germany

Location

Medizinische Hochschule Hannover

Hanover, Germany

Location

Universitätsklinikum Jena

Jena, Germany

Location

Universität Ulm

Ulm, Germany

Location

Trinity College Dublin

Dublin, Ireland

Location

IRCCS Istituto Auxologico Italiano

Milan, Italy

Location

NEuroMuscular Omnicentre. Fondazione Serena Onlus

Milan, Italy

Location

AOU Università degli Studi della Campania "Luigi Vanvitelli"

Napoli, Italy

Location

IRCCS Istituto Clinico Humanitas

Rozzano, Italy

Location

Azienda Ospedaliera Santa Maria di Terni

Terni, Italy

Location

AOU Città della Salute e della Scienza di Torino

Torino, Italy

Location

Universitair Medisch Centrum Utrecht

Utrecht, Netherlands

Location

The Walton Centre NHS Foundation Trust

Liverpool, United Kingdom

Location

Plymouth Hospitals NHS Trust

Plymouth, United Kingdom

Location

Lancashire Teaching Hospitals NHS Foundation Trust

Preston, United Kingdom

Location

Salford Royal NHS Foundation Trust

Salford, United Kingdom

Location

University of Sheffield

Sheffield, United Kingdom

Location

Royal Stoke University Hospital

Stoke, United Kingdom

Location

Related Publications (2)

  • Albanese A, Ludolph AC, McDermott CJ, Corcia P, Van Damme P, Van den Berg LH, Hardiman O, Rinaldi G, Vanacore N, Dickie B; TUDCA-ALS Study Group. Tauroursodeoxycholic acid in patients with amyotrophic lateral sclerosis: The TUDCA-ALS trial protocol. Front Neurol. 2022 Sep 27;13:1009113. doi: 10.3389/fneur.2022.1009113. eCollection 2022.

    PMID: 36237618BACKGROUND

  • Lombardo FL, Spila Alegiani S, Mayer F, Cipriani M, Lo Giudice M, Ludolph AC, McDermott CJ, Corcia P, Van Damme P, Van den Berg LH, Hardiman O, Nicolini G, Vanacore N, Dickie B, Albanese A, Puopolo M; TUDCA-ALS Study Group. 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. Trials. 2023 Dec 5;24(1):792. doi: 10.1186/s13063-023-07638-w.

    PMID: 38053196DERIVED

Related Links

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

ursodoxicoltaurine

Condition Hierarchy (Ancestors)

Spinal Cord DiseasesCentral Nervous System DiseasesNervous System DiseasesMotor Neuron DiseaseNeurodegenerative DiseasesTDP-43 ProteinopathiesNeuromuscular DiseasesProteostasis DeficienciesMetabolic DiseasesNutritional and Metabolic Diseases

Study Officials

  • Alberto Albanese, MD

    Humanitas Mirasole SpA

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 4, 2019

First Posted

January 11, 2019

Study Start

February 22, 2019

Primary Completion

December 31, 2023

Study Completion

December 31, 2023

Last Updated

July 10, 2023

Record last verified: 2023-07

Data Sharing

IPD Sharing
Will share

Once the dataset has been analysed, a complete, cleaned, anonymized copy of the final data used in conducting the final analyses will be made available to be used in further studies by the research partners or by other research groups and clinicians. To prevent misuse and misinterpretation, relevant study metadata (such as the study protocol, case report forms, documentation providing information about the methodology and procedures used to collect the data, definition of variables and statistical code) will be shared in a data repository with a stable URL. Patient anonymity and legal compliance will be assured throughout all the steps of data transfer.

Shared Documents
STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
Time Frame
Three months after the data-entry process and final data curation
Access Criteria
Data will be made available only to qualified designated persons (methodologists, biostatisticians) from other academic institutions, on request. User registration will be required in order to access files.

Locations

NL(1)IE(1)GB(6)DE(6)FR(4)BE(1)IT(6)