Study Purpose:
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).Study Status:
Not recruiting
Disease:
Amyotrophic Lateral Sclerosis (ALS)
Study Type:
Interventional
Type of Intervention:
Drug
Intervention Name:
Tauroursodeoxycholic Acid, Placebo
Placebo:
Yes
Phase:
Phase 3
Study Chair(s)/Principal Investigator(s):
Alberto Albanese, MD, Humanitas Mirasole SpA
Clinicaltrials.gov ID:
Neals Affiliated?
No
Coordinating Center Contact Information
Full Study Summary:
TUDCA will be administered orally at the dose of 1 g twice daily (2 g daily) for 18 months. Patients will be taking also riluzole at the dose of 50 mg twice daily (100 mg daily).
Patient randomization will take place after a screening (lead-in) period of 12 weeks (3 months) with 3 assessments at 6-week intervals. Clinical assessments during the trial phase will be performed every three months. This will allow measuring the progression rate before and after starting treatment (either active or placebo).
Study Sponsor:
Humanitas Mirasole SpA
Estimated Enrollment:
337
Estimated Study Start Date:
02 / 22 / 2019
Estimated Study Completion Date:
12 / 30 / 2022
Posting Last Modified Date:
10 / 19 / 2022
Date Study Added to neals.org:
01 / 11 / 2019
Minimum Age:
18 Years
Maximum Age:
80 Years
Inclusion Criteria:- Probable laboratory-supported, probable, or definite ALS, as defined by El Escorial Revised ALS diagnostic criteria 34
- Disease duration ≤ 18 months
- No swallowing difficulty (4 at ALSFRS-R swallowing subscore)
- Able to perform reproducible pulmonary function tests
- Forced vital capacity ≥70% of normal
- Stable on riluzole treatment for 3 months in the lead-in period
- Able to perform reproducible pulmonary function tests
- Signed informed consent
Exclusion Criteria:
- 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
- At the time of screening, 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 at time of enrolment
- Occurrence of frequent biliary colic, biliary infections, severe pancreatic abnormalities
- Subjects who weigh 88 lbs (40 kg) or less at screening
- Aspartate aminotransferase or alanine aminotransferase concentrations more than 3 times the upper limit of normal
- Creatinine clearance 50 ml/min or less
- Previous exposure to bile acids
- Any clinically significant neurological, haematological, autoimmune, endocrine, cardiovascular, neoplastic, renal, gastrointestinal, or other disorder that, in the Investigator's opinion, could interfere with the subject's participation in the study, place the subject at increased risk, or confound interpretation of study results
- Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive TUDCA or that the subject is unable or unlikely to comply with the dosing schedule or study evaluations
- The patient is sexually active and is not willing to use highly effective contraception during the study and up to 90 days after the day of last dose
Katholieke Universiteit Leuven
Leuven
Belgium
Centre Hospitalier Universitaire de Bordeaux
Bordeaux
France
Centre Hospitalier Universitaire Limoges
Limoges
France
Centre Hospitalier Universitaire de Montpellier
Montpellier
France
Centre Hospitalier Regional Universitaire de Tours
Tours
France
Charité - Universitätsmedizin Berlin
Berlin
Germany
Universitätsklinikum Carl Gustav Carus Dresden
Dresden
Germany
Alfried Krupp Krankenhaus Rüttenscheid
Essen
Germany
Medizinische Hochschule Hannover
Hannover
Germany
Universitätsklinikum Jena
Jena
Germany
Universität Ulm
Ulm
Germany
Trinity College Dublin
Dublin
Ireland
IRCCS Istituto Auxologico Italiano
Milano
Italy
NEuroMuscular Omnicentre. Fondazione Serena Onlus
Milano
Italy
AOU Università degli Studi della Campania "Luigi Vanvitelli"
Napoli
Italy
IRCCS Istituto Clinico Humanitas
Rozzano
Italy
Azienda Ospedaliera Santa Maria di Terni
Terni
Italy
AOU Città della Salute e della Scienza di Torino
Torino
Italy
Universitair Medisch Centrum Utrecht
Utrecht
Netherlands
The Walton Centre NHS Foundation Trust
Liverpool
United Kingdom
Plymouth Hospitals NHS Trust
Plymouth
United Kingdom
Lancashire Teaching Hospitals NHS Foundation Trust
Preston
United Kingdom
Salford Royal NHS Foundation Trust
Salford
United Kingdom
University of Sheffield
Sheffield
United Kingdom
Royal Stoke University Hospital
Stoke
United Kingdom