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Trial record 2 of 27 for:    TUDCA

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03800524
Recruitment Status : Recruiting
First Posted : January 11, 2019
Last Update Posted : February 12, 2020
Sponsor:
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
Information provided by (Responsible Party):
Humanitas Mirasole SpA

Tracking Information
First Submitted Date  ICMJE January 4, 2019
First Posted Date  ICMJE January 11, 2019
Last Update Posted Date February 12, 2020
Actual Study Start Date  ICMJE February 22, 2019
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 8, 2019)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 12, 2019)
  • Survival time [ Time Frame: 18 months ]
    Survival time measured by death or respiratory insufficiency
  • ALS disease functional rating scale - revised version (ALSFRS-R) [ Time Frame: 18 months ]
    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.
  • ALS Assessment Questionnaire‐40 (ALSAQ-40) [ Time Frame: 18 months ]
    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).
  • Forced Vital Capacity [ Time Frame: 18 months ]
    Difference in change from baseline in Forced Vital Capacity
  • EuroQol 5‐Dimension-5 Levels (EQ-5D-5L) scale [ Time Frame: 18 months ]
    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.
  • Medical Research Council (MRC) scale [ Time Frame: 18 months ]
    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).
  • Neurofilaments levels [ Time Frame: 18 months ]
    Effect of TUDCA on Neurofilament levels in comparison to placebo
  • MMP-9 levels [ Time Frame: 18 months ]
    Effect of TUDCA on MMP-9 expression in comparison to placebo
Original Secondary Outcome Measures  ICMJE
 (submitted: January 8, 2019)
  • Survival time [ Time Frame: 18 months ]
    Survival time measured by death or respiratory insufficiency
  • ALS disease functional rating scale - revised version (ALSFRS-R) [ Time Frame: 18 months ]
    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.
  • ALS Assessment Questionnaire‐40 (ALSAQ-40) [ Time Frame: 18 months ]
    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 pa-tient 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).
  • Forced Vital Capacity [ Time Frame: 18 months ]
    Difference in change from baseline in Forced Vital Capacity
  • EuroQol 5‐Dimension-5 Levels (EQ-5D-5L) scale [ Time Frame: 18 months ]
    Difference in change from baseline in EQ-5D-5L scale. The EQ-5D-5L descriptive system comprises 5 dimensions (mobility, self-care, usual activi-ties, 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 express-ing 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.
  • Medical Research Council (MRC) scale [ Time Frame: 18 months ]
    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).
  • Neurofilaments levels [ Time Frame: 18 months ]
    Effect of TUDCA on Neurofilament levels in comparison to placebo
  • MMP-9 levels [ Time Frame: 18 months ]
    Effect of TUDCA on MMP-9 expression in comparison to placebo
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of TUDCA as add-on Treatment in Patients Affected by ALS
Official Title  ICMJE Safety and Efficacy of Tauroursodeoxycholic (TUDCA) as add-on Treatment in Patients Affected by Amyotrophic Lateral Sclerosis (ALS)
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).
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Amyotrophic Lateral Sclerosis (ALS)
Intervention  ICMJE
  • 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
    Other Names:
    • TUDCA
    • Tudcabil
    • Taurolite
  • 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
Study Arms  ICMJE
  • Experimental: 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
    Intervention: Drug: Tauroursodeoxycholic Acid
  • Placebo Comparator: 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
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 8, 2019)
440
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2021
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Alberto Albanese, MD +39-0282246418 alberto.albanese@humanitas.it
Contact: Paolo Tornese, PhD +39-0282246422 paolo.tornese@humanitas.it
Listed Location Countries  ICMJE Belgium,   France,   Germany,   Ireland,   Italy,   Netherlands,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03800524
Other Study ID Numbers  ICMJE H2020/755094/2017/IT-01
2018-002722-22 ( EudraCT Number )
755094 ( Other Grant/Funding Number: European Commission )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

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.

Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Supporting Materials: 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.
Responsible Party Humanitas Mirasole SpA
Study Sponsor  ICMJE Humanitas Mirasole SpA
Collaborators  ICMJE
  • 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
Investigators  ICMJE
Study Chair: Alberto Albanese, MD Humanitas Mirasole SpA
PRS Account Humanitas Mirasole SpA
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP