Amyotrophic Lateral Sclerosis (ALS)Phase 3TUDCA-ALSNCT03800524
Safety and Efficacy of TUDCA as add-on Treatment in Patients Affected by ALS
A Phase 3 study testing Tauroursodeoxycholic Acid in people with Amyotrophic Lateral Sclerosis (ALS), run by Humanitas Mirasole SpA at 25 sites in 7 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis (ALS)
- What is being tested?
- Tauroursodeoxycholic Acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 337 participants
- Where
- 25 sitesin 7 countries
- Study dates
- 22 Feb 2019to 31 Dec 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 25Show fewer
- 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
Trial locations and contacts
25 sites in 7 countries.
25 sites in 7 countries
Germany6 sites
Charité - Universitätsmedizin Berlin
Berlin
Universitätsklinikum Carl Gustav Carus Dresden
Dresden
Alfried Krupp Krankenhaus Rüttenscheid
Essen
Medizinische Hochschule Hannover
Hanover
Universitätsklinikum Jena
Jena
Universität Ulm
Ulm
Italy6 sites
IRCCS Istituto Auxologico Italiano
Milan
NEuroMuscular Omnicentre. Fondazione Serena Onlus
Milan
AOU Università degli Studi della Campania "Luigi Vanvitelli"
Naples
IRCCS Istituto Clinico Humanitas
Rozzano
Azienda Ospedaliera Santa Maria di Terni
Terni
AOU Città della Salute e della Scienza di Torino
Torino
United Kingdom6 sites
The Walton Centre NHS Foundation Trust
Liverpool
Plymouth Hospitals NHS Trust
Plymouth
Lancashire Teaching Hospitals NHS Foundation Trust
Preston
Salford Royal NHS Foundation Trust
Salford
University of Sheffield
Sheffield
Royal Stoke University Hospital
Stoke
France4 sites
Centre Hospitalier Universitaire de Bordeaux
Bordeaux
Centre Hospitalier Universitaire Limoges
Limoges
Centre Hospitalier Universitaire de Montpellier
Montpellier
Centre Hospitalier Regional Universitaire de Tours
Tours
About this study
Official title: Safety and Efficacy of Tauroursodeoxycholic (TUDCA) as add-on Treatment in Patients Affected by Amyotrophic Lateral Sclerosis (ALS)
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).
Read the detailed description
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
- Amyotrophic Lateral Sclerosis (ALS)
- Being tested
- Tauroursodeoxycholic Acid, Placebo
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tauroursodeoxycholic AcidDrug
Also called TUDCA, Tudcabil, Taurolite
- 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
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of responder patients
Identification of the responder patients defined as those showing an improvement of at least 20% in the ALSFRS-R slope
Measured: 18 months
Secondary outcomes (9)
Survival time
Survival time measured by death or respiratory insufficiency
Measured: 18 months
ALS disease functional rating scale - revised version (ALSFRS-R)
Difference in change from baseline in ALSFRS-R. Each task of the scale is rated on a five-point scale from 0 = can't do, to 4 = normal ability. Individual item scores are summed to produce a reported score ranging from 0 = worst to 48 = best.
Measured: 18 months
ALS Assessment Questionnaire-40 (ALSAQ-40)
Difference in change from baseline in ALSAQ-40. The instrument contains 40 statements that measure five dimensions of health state: Physical Mobility (10 statements), Activities of Daily Living and Independence (10 statements), Eating and Drinking (5 statements), Communication (5 statements), Emotional Functioning (10 statements). The patient must indicate how often (Never, Rarely, Sometimes, Often, or Always) the statement have been true. Dimension scores are coded on a likert scale, ranging from 0 (best health as assessed by the scale) to 100 (worse health as assessed by the measure).
Measured: 18 months
Forced Vital Capacity
Difference in change from baseline in Forced Vital Capacity
Measured: 18 months
EuroQol 5-Dimension-5 Levels (EQ-5D-5L) scale
Difference in change from baseline in EQ-5D-5L scale. The EQ-5D-5L descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). Each dimension has 5 levels: 1.no problems, 2.slight problems, 3.moderate problems, 4.severe problems, 5.extreme problems. The patient is asked to indicate his/her health state by ticking (or placing a cross) in the box against the most appropriate statement in each of the 5 dimensions. This decision results in a 1-digit number expressing the level selected for that dimension. The digits for 5 dimensions can be combined in a 5-digit number describing the patient health state. Numbers 1-5 have no arithmetic properties and should not be used as a cardinal score.
Measured: 18 months
Medical Research Council (MRC) scale
Difference in change from baseline in muscle force assessed by the MRC scale. The scale rates muscle strength of 6 muscles (3 at the upper and 3 at the lower limbs), bilaterally. Each muscle is graded from 0 = no movement, to 5 = normal strength, giving a total sum-score that ranges from 0 (total paralysis) to 60 (normal strength).
Measured: 18 months
Neurofilaments levels
Effect of TUDCA on Neurofilament levels in comparison to placebo
Measured: 18 months
MMP-9 levels
Effect of TUDCA on MMP-9 expression in comparison to placebo
Measured: 18 months
Long-term safety and tolerability
assessed through adverse reaction, concomitant treatment, physical examination, vital signs and routine haematology and biochemistry analyses
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2019
- Study start22 Feb 2019
- Primary completion31 Dec 2023 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Amyotrophic Lateral Sclerosis (ALS)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 337 participants (actual)
Sponsor and investigators
- Lead sponsor
- Humanitas Mirasole SpA
- Sponsor type
- University, hospital or other
- Collaborators
- University of Ulm, University of Sheffield, University Hospital, Tours, KU Leuven, UMC Utrecht, University of Dublin, Trinity College, Bruschettini S.r.l., Istituto Superiore di Sanità, Motor Neurone Disease Association, European Commission
- Responsible party
- Sponsor
- Investigators
- Alberto Albanese, MD, Study chair, Humanitas Mirasole SpA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03800524
- Sponsor's protocol ID
- H2020/755094/2017/IT-01
- Other IDs
- 2018-002722-22, 755094, 2018
- Acronym
- TUDCA-ALS
- Status last verified
- Jul 2023
- First submitted
- 4 Jan 2019
- Last updated
- 10 Jul 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 36237618Lombardo 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.
PubMed 38053196
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Tauroursodeoxycholic (TUDCA) as add-on Treatment in Patients Affected by Amyotrophic Lateral Sclerosis (ALS)
- ClinicalTrials.gov ID
- NCT03800524
- Acronym / sponsor ID
- TUDCA-ALS / H2020/755094/2017/IT-01
- Conditions
- Amyotrophic Lateral Sclerosis (ALS)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 337 participants (actual)
- Lead sponsor
- Humanitas Mirasole SpAUniversity, hospital or other
- Collaborators
- University of Ulm, University of Sheffield, University Hospital, Tours, KU Leuven, UMC Utrecht, University of Dublin, Trinity College, Bruschettini S.r.l., Istituto Superiore di Sanità, Motor Neurone Disease Association, European Commission
- Study start
- 22 Feb 2019 (actual)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 11 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tauroursodeoxycholic acid (TUDCA) | Experimental | Drug: 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 |
| Reference therapy | Placebo comparator | Drug: Placebo* 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 |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (25 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tauroursodeoxycholic AcidAlso: TUDCA, Tudcabil, Taurolite* 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 (TUDCA) |
| 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 | Drug | Reference therapy |
Primary outcome
Number of responder patients
Time frame: 18 months
Identification of the responder patients defined as those showing an improvement of at least 20% in the ALSFRS-R slope
9 secondary outcomes
Survival time
Time frame: 18 months
ALS disease functional rating scale - revised version (ALSFRS-R)
Time frame: 18 months
ALS Assessment Questionnaire-40 (ALSAQ-40)
Time frame: 18 months
Forced Vital Capacity
Time frame: 18 months
EuroQol 5-Dimension-5 Levels (EQ-5D-5L) scale
Time frame: 18 months
Medical Research Council (MRC) scale
Time frame: 18 months
Neurofilaments levels
Time frame: 18 months
MMP-9 levels
Time frame: 18 months
Long-term safety and tolerability
Time frame: 18 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2023.
- Background: PubMed 36237618Albanese 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.
- Derived from this study: PubMed 38053196Lombardo 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.
- TUDCA-ALS Consortium websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alberto Albanese, MD study chair
Humanitas Mirasole SpA
25 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tauroursodeoxycholic Acid in people with Amyotrophic Lateral Sclerosis (ALS), run by Humanitas Mirasole SpA at 25 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in Germany, Italy, United Kingdom, France, Belgium and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of responder patients (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03800524, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2023.