<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03800524</url>
  </required_header>
  <id_info>
    <org_study_id>H2020/755094/2017/IT-01</org_study_id>
    <secondary_id>2018-002722-22</secondary_id>
    <secondary_id>755094</secondary_id>
    <nct_id>NCT03800524</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of TUDCA as add-on Treatment in Patients Affected by ALS</brief_title>
  <acronym>TUDCA-ALS</acronym>
  <official_title>Safety and Efficacy of Tauroursodeoxycholic (TUDCA) as add-on Treatment in Patients Affected by Amyotrophic Lateral Sclerosis (ALS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Humanitas Mirasole SpA</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Ulm</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Sheffield</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital, Tours</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>KU Leuven</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>UMC Utrecht</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Dublin, Trinity College</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Bruschettini S.r.l.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Istituto Superiore di Sanità</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Motor Neurone Disease Association</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>European Commission</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Humanitas Mirasole SpA</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase III, multi-centre, randomized, double-blind, placebo-controlled,&#xD;
      parallel-group study to evaluate Safety and Efficacy of Tauroursodeoxycholic (TUDCA) as&#xD;
      add-on Treatment in Patients Affected by Amyotrophic Lateral Sclerosis (ALS).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Enrolled patients will be randomized to one of two treatment arms: TUDCA or identical placebo&#xD;
      by oral route. The randomization will be performed in a ratio one to one for the two arms.&#xD;
&#xD;
      TUDCA will be administered orally at the dose of 1 g twice daily (2 g daily) for 18 months.&#xD;
      Patients will be taking also riluzole at the dose of 50 mg twice daily (100 mg daily).&#xD;
&#xD;
      Patient randomization will take place after a screening (lead-in) period of 12 weeks (3&#xD;
      months) with 3 assessments at 6-week intervals. Clinical assessments during the trial phase&#xD;
      will be performed every three months. This will allow measuring the progression rate before&#xD;
      and after starting treatment (either active or placebo).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">February 22, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of responder patients</measure>
    <time_frame>18 months</time_frame>
    <description>Identification of the responder patients defined as those showing an improvement of at least 20% in the ALSFRS-R slope</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Survival time</measure>
    <time_frame>18 months</time_frame>
    <description>Survival time measured by death or respiratory insufficiency</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ALS disease functional rating scale - revised version (ALSFRS-R)</measure>
    <time_frame>18 months</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ALS Assessment Questionnaire-40 (ALSAQ-40)</measure>
    <time_frame>18 months</time_frame>
    <description>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).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Forced Vital Capacity</measure>
    <time_frame>18 months</time_frame>
    <description>Difference in change from baseline in Forced Vital Capacity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EuroQol 5-Dimension-5 Levels (EQ-5D-5L) scale</measure>
    <time_frame>18 months</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Medical Research Council (MRC) scale</measure>
    <time_frame>18 months</time_frame>
    <description>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).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neurofilaments levels</measure>
    <time_frame>18 months</time_frame>
    <description>Effect of TUDCA on Neurofilament levels in comparison to placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MMP-9 levels</measure>
    <time_frame>18 months</time_frame>
    <description>Effect of TUDCA on MMP-9 expression in comparison to placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Long-term safety and tolerability</measure>
    <time_frame>18 months</time_frame>
    <description>assessed through adverse reaction, concomitant treatment, physical examination, vital signs and routine haematology and biochemistry analyses</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">337</enrollment>
  <condition>Amyotrophic Lateral Sclerosis (ALS)</condition>
  <arm_group>
    <arm_group_label>Tauroursodeoxycholic acid (TUDCA)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tauroursodeoxycholic acid (TUDCA) 250 mg capsules&#xD;
Doses: 4 capsules (1 g) twice daily 10-15 minutes after a meal&#xD;
Mode of administration: orally&#xD;
Duration: 18 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Reference therapy</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo capsules identical to active compound&#xD;
Doses: 4 capsules (1 g) twice daily 10-15 minutes after a meal&#xD;
Mode of administration: orally&#xD;
Duration: 18 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tauroursodeoxycholic Acid</intervention_name>
    <description>Tauroursodeoxycholic acid (TUDCA) 250 mg capsules&#xD;
Doses: 4 capsules (1 g) twice daily 10-15 minutes after a meal&#xD;
Mode of administration: orally&#xD;
Duration: 18 months</description>
    <arm_group_label>Tauroursodeoxycholic acid (TUDCA)</arm_group_label>
    <other_name>TUDCA</other_name>
    <other_name>Tudcabil</other_name>
    <other_name>Taurolite</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo 250 mg capsules&#xD;
Doses: 4 capsules (1 g) twice daily 10-15 minutes after a meal&#xD;
Mode of administration: orally&#xD;
Duration: 18 months</description>
    <arm_group_label>Reference therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Probable laboratory-supported, probable, or definite ALS, as defined by El Escorial&#xD;
             Revised ALS diagnostic criteria at screening visit (month -3)&#xD;
&#xD;
          -  Disease duration ≤ 18 months at screening visit (month -3)&#xD;
&#xD;
          -  Able to perform reproducible pulmonary function tests at screening visit (month -3)&#xD;
&#xD;
          -  Forced vital capacity or slow vital capacity ≥70% of normal at screening visit (month&#xD;
             -3)&#xD;
&#xD;
          -  Stable on riluzole treatment for 3 months in the lead-in period&#xD;
&#xD;
          -  Signed informed consent at screening visit (month -3)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Treatment with edaravone&#xD;
&#xD;
          -  Other causes of neuromuscular weakness&#xD;
&#xD;
          -  Presence of other neurodegenerative diseases&#xD;
&#xD;
          -  Significant cognitive impairment, clinical dementia or psychiatric illness&#xD;
&#xD;
          -  Severe cardiac or pulmonary disease&#xD;
&#xD;
          -  Other diseases precluding functional assessments&#xD;
&#xD;
          -  Other life-threatening diseases&#xD;
&#xD;
          -  Any use of non-invasive ventilation (e.g. continuous positive airway pressure,&#xD;
             non-invasive bi-level positive airway pressure or non-invasive volume ventilation) for&#xD;
             any portion of the day, or mechanical ventilation via tracheostomy, or on any form of&#xD;
             oxygen supplementation&#xD;
&#xD;
          -  Gastrointestinal disorder that is likely to impair absorption of study drug from the&#xD;
             gastrointestinal tract&#xD;
&#xD;
          -  Has taken any investigational study drug within 30 days or five half-lives of the&#xD;
             prior agent, whichever is longer, prior to dosing&#xD;
&#xD;
          -  Any clinically significant laboratory abnormality&#xD;
&#xD;
          -  Other concurrent investigational medications&#xD;
&#xD;
          -  Active peptic ulcer&#xD;
&#xD;
          -  Previous surgery or infections of small intestine&#xD;
&#xD;
          -  Patients unable to easily swallow the treatment pills&#xD;
&#xD;
          -  Acute inflammation of the gallbladder or bile ducts&#xD;
&#xD;
          -  Occurrence of frequent biliary colic, biliary infections, severe pancreatic&#xD;
             abnormalities&#xD;
&#xD;
          -  Bile duct obstruction, calcified X-ray opaque gallstones and reduced mobility of the&#xD;
             gallbladder&#xD;
&#xD;
          -  Subjects who weigh 88 lbs (40 kg) or less&#xD;
&#xD;
          -  Aspartate aminotransferase or alanine aminotransferase concentrations more than 3&#xD;
             times the upper limit of normal&#xD;
&#xD;
          -  Creatinine clearance 50 ml/min or less&#xD;
&#xD;
          -  Any clinically significant neurological, haematological, autoimmune, endocrine,&#xD;
             cardiovascular, neoplastic, renal, gastrointestinal, or other disorder that, in the&#xD;
             Investigator's opinion, could interfere with the subject's participation in the study,&#xD;
             place the subject at increased risk, or confound interpretation of study results&#xD;
&#xD;
          -  Consideration by the investigator, for any reason, that the subject is an unsuitable&#xD;
             candidate to receive TUDCA or that the subject is unable or unlikely to comply with&#xD;
             the dosing schedule or study evaluations&#xD;
&#xD;
          -  The patient of reproductive potential is sexually active and is not willing to use&#xD;
             highly effective contraception during the study and up to 90 days after the day of&#xD;
             last dose&#xD;
&#xD;
          -  The patient is pregnant or breast feeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alberto Albanese, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Humanitas Mirasole SpA</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Katholieke Universiteit Leuven</name>
      <address>
        <city>Leuven</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Universitaire de Bordeaux</name>
      <address>
        <city>Bordeaux</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Universitaire Limoges</name>
      <address>
        <city>Limoges</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Universitaire de Montpellier</name>
      <address>
        <city>Montpellier</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Regional Universitaire de Tours</name>
      <address>
        <city>Tours</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charité - Universitätsmedizin Berlin</name>
      <address>
        <city>Berlin</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Carl Gustav Carus Dresden</name>
      <address>
        <city>Dresden</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alfried Krupp Krankenhaus Rüttenscheid</name>
      <address>
        <city>Essen</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Hochschule Hannover</name>
      <address>
        <city>Hannover</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Jena</name>
      <address>
        <city>Jena</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universität Ulm</name>
      <address>
        <city>Ulm</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Trinity College Dublin</name>
      <address>
        <city>Dublin</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRCCS Istituto Auxologico Italiano</name>
      <address>
        <city>Milano</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NEuroMuscular Omnicentre. Fondazione Serena Onlus</name>
      <address>
        <city>Milano</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AOU Università degli Studi della Campania &quot;Luigi Vanvitelli&quot;</name>
      <address>
        <city>Napoli</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRCCS Istituto Clinico Humanitas</name>
      <address>
        <city>Rozzano</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Santa Maria di Terni</name>
      <address>
        <city>Terni</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AOU Città della Salute e della Scienza di Torino</name>
      <address>
        <city>Torino</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitair Medisch Centrum Utrecht</name>
      <address>
        <city>Utrecht</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Walton Centre NHS Foundation Trust</name>
      <address>
        <city>Liverpool</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Plymouth Hospitals NHS Trust</name>
      <address>
        <city>Plymouth</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lancashire Teaching Hospitals NHS Foundation Trust</name>
      <address>
        <city>Preston</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Salford Royal NHS Foundation Trust</name>
      <address>
        <city>Salford</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Sheffield</name>
      <address>
        <city>Sheffield</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Stoke University Hospital</name>
      <address>
        <city>Stoke</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>France</country>
    <country>Germany</country>
    <country>Ireland</country>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>United Kingdom</country>
  </location_countries>
  <link>
    <url>http://www.tudca.eu/</url>
    <description>TUDCA-ALS Consortium website</description>
  </link>
  <reference>
    <citation>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.</citation>
    <PMID>36237618</PMID>
  </reference>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>January 4, 2019</study_first_submitted>
  <study_first_submitted_qc>January 8, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 11, 2019</study_first_posted>
  <last_update_submitted>July 7, 2023</last_update_submitted>
  <last_update_submitted_qc>July 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Motor Neuron Disease</mesh_term>
    <mesh_term>Amyotrophic Lateral Sclerosis</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ursodoxicoltaurine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_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.&#xD;
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.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>Three months after the data-entry process and final data curation</ipd_time_frame>
    <ipd_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.</ipd_access_criteria>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03800524
org study id: H2020/755094/2017/IT-01
secondary id: 2018-002722-22
secondary id: 755094
nct id: NCT03800524
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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).
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).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of responder patients
time frame: 18 months
description: Identification of the responder patients defined as those showing an improvement of at least 20% in the ALSFRS-R slope
measure: Survival time
time frame: 18 months
description: Survival time measured by death or respiratory insufficiency
measure: ALS disease functional rating scale - revised version (ALSFRS-R)
time frame: 18 months
description: 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.
measure: ALS Assessment Questionnaire-40 (ALSAQ-40)
time frame: 18 months
description: 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).
measure: Forced Vital Capacity
time frame: 18 months
description: Difference in change from baseline in Forced Vital Capacity
measure: EuroQol 5-Dimension-5 Levels (EQ-5D-5L) scale
time frame: 18 months
description: 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.
measure: Medical Research Council (MRC) scale
time frame: 18 months
description: 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).
measure: Neurofilaments levels
time frame: 18 months
description: Effect of TUDCA on Neurofilament levels in comparison to placebo
measure: MMP-9 levels
time frame: 18 months
description: Effect of TUDCA on MMP-9 expression in comparison to placebo
measure: Long-term safety and tolerability
time frame: 18 months
description: assessed through adverse reaction, concomitant treatment, physical examination, vital signs and routine haematology and biochemistry analyses
arm group label: Tauroursodeoxycholic acid (TUDCA)
arm group type: Experimental
description: 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
arm group label: Reference therapy
arm group type: Placebo Comparator
description: 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 type: Drug
intervention name: Tauroursodeoxycholic Acid
description: 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
arm group label: Tauroursodeoxycholic acid (TUDCA)
other name: TUDCA
other name: Tudcabil
other name: Taurolite
intervention type: Drug
intervention name: Placebo
description: Placebo 250 mg capsules
Doses: 4 capsules (1 g) twice daily 10-15 minutes after a meal
Mode of administration: orally
Duration: 18 months
arm group label: Reference therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Alberto Albanese, MD
role: Study Chair
affiliation: Humanitas Mirasole SpA
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country: Belgium
country: France
country: Germany
country: Ireland
country: Italy
country: Netherlands
country: United Kingdom
url: http://www.tudca.eu/
description: TUDCA-ALS Consortium website
citation: 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: 36237618
responsible party type: Sponsor
mesh term: Motor Neuron Disease
mesh term: Amyotrophic Lateral Sclerosis
mesh term: Sclerosis
mesh term: Ursodoxicoltaurine
sharing ipd: Yes
ipd 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.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: Three months after the data-entry process and final data curation
ipd 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.