Safety and Efficacy of TUDCA as add-on Treatment in Patients Affected by ALS

NCT ID: NCT03800524

Last Updated: 2023-07-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

337 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-02-22

Study Completion Date

2023-12-31

Brief Summary

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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).

Detailed Description

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Enrolled patients will be randomized to one of two treatment arms: TUDCA or identical placebo by oral route. The randomization will be performed in a ratio one to one for the two arms.

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).

Conditions

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Amyotrophic Lateral Sclerosis (ALS)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Tauroursodeoxycholic acid (TUDCA)

* 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

Group Type EXPERIMENTAL

Tauroursodeoxycholic Acid

Intervention Type DRUG

* 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

Reference therapy

* 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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

Interventions

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Tauroursodeoxycholic Acid

* 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

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

Other Intervention Names

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TUDCA Tudcabil Taurolite

Eligibility Criteria

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Inclusion Criteria

* 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)

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
* 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
* Acute inflammation of the gallbladder or bile ducts
* Occurrence of frequent biliary colic, biliary infections, severe pancreatic abnormalities
* Bile duct obstruction, calcified X-ray opaque gallstones and reduced mobility of the gallbladder
* Subjects who weigh 88 lbs (40 kg) or less
* Aspartate aminotransferase or alanine aminotransferase concentrations more than 3 times the upper limit of normal
* Creatinine clearance 50 ml/min or less
* 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 of reproductive potential 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
* The patient is pregnant or breast feeding
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Ulm

OTHER

Sponsor Role collaborator

University of Sheffield

OTHER

Sponsor Role collaborator

University Hospital, Tours

OTHER

Sponsor Role collaborator

KU Leuven

OTHER

Sponsor Role collaborator

UMC Utrecht

OTHER

Sponsor Role collaborator

University of Dublin, Trinity College

OTHER

Sponsor Role collaborator

Bruschettini S.r.l.

UNKNOWN

Sponsor Role collaborator

Istituto Superiore di Sanità

OTHER

Sponsor Role collaborator

Motor Neurone Disease Association

UNKNOWN

Sponsor Role collaborator

European Commission

OTHER

Sponsor Role collaborator

Humanitas Mirasole SpA

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Alberto Albanese, MD

Role: STUDY_CHAIR

Humanitas Mirasole SpA

Locations

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Katholieke Universiteit Leuven

Leuven, , Belgium

Site Status

Centre Hospitalier Universitaire de Bordeaux

Bordeaux, , France

Site Status

Centre Hospitalier Universitaire Limoges

Limoges, , France

Site Status

Centre Hospitalier Universitaire de Montpellier

Montpellier, , France

Site Status

Centre Hospitalier Regional Universitaire de Tours

Tours, , France

Site Status

Charité - Universitätsmedizin Berlin

Berlin, , Germany

Site Status

Universitätsklinikum Carl Gustav Carus Dresden

Dresden, , Germany

Site Status

Alfried Krupp Krankenhaus Rüttenscheid

Essen, , Germany

Site Status

Medizinische Hochschule Hannover

Hanover, , Germany

Site Status

Universitätsklinikum Jena

Jena, , Germany

Site Status

Universität Ulm

Ulm, , Germany

Site Status

Trinity College Dublin

Dublin, , Ireland

Site Status

IRCCS Istituto Auxologico Italiano

Milan, , Italy

Site Status

NEuroMuscular Omnicentre. Fondazione Serena Onlus

Milan, , Italy

Site Status

AOU Università degli Studi della Campania "Luigi Vanvitelli"

Napoli, , Italy

Site Status

IRCCS Istituto Clinico Humanitas

Rozzano, , Italy

Site Status

Azienda Ospedaliera Santa Maria di Terni

Terni, , Italy

Site Status

AOU Città della Salute e della Scienza di Torino

Torino, , Italy

Site Status

Universitair Medisch Centrum Utrecht

Utrecht, , Netherlands

Site Status

The Walton Centre NHS Foundation Trust

Liverpool, , United Kingdom

Site Status

Plymouth Hospitals NHS Trust

Plymouth, , United Kingdom

Site Status

Lancashire Teaching Hospitals NHS Foundation Trust

Preston, , United Kingdom

Site Status

Salford Royal NHS Foundation Trust

Salford, , United Kingdom

Site Status

University of Sheffield

Sheffield, , United Kingdom

Site Status

Royal Stoke University Hospital

Stoke, , United Kingdom

Site Status

Countries

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Belgium France Germany Ireland Italy Netherlands United Kingdom

References

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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.

Reference Type BACKGROUND
PMID: 36237618 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38053196 (View on PubMed)

Related Links

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http://www.tudca.eu/

TUDCA-ALS Consortium website

Other Identifiers

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2018-002722-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

755094

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

H2020/755094/2017/IT-01

Identifier Type: -

Identifier Source: org_study_id

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