<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/NCT04456582</url>
  </required_header>
  <id_info>
    <org_study_id>4963/19/182</org_study_id>
    <nct_id>NCT04456582</nct_id>
  </id_info>
  <brief_title>Noninvasive Assessment of Myocardial Stiffness by 2D-SWE Ultrasound Technique (Bidimensional Shear Wave Elastography) in Patients With Transthyretin Amyloidosis</brief_title>
  <acronym>ELAST-2D</acronym>
  <official_title>Noninvasive Assessment of Myocardial Stiffness by 2D-SWE Ultrasound Technique (Bidimensional Shear Wave Elastography) in Patients With Transthyretin Amyloidosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fábio Fernandes</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Sao Paulo General Hospital</source>
  <oversight_info>
    <has_dmc>No</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>
      Amyloidosis by mutation of the transthyretin gene (ATTRh) is part of a group of diseases in&#xD;
      which the deposit of structurally abnormal proteins (amyloid fibrils) affects multiple organs&#xD;
      such as: liver, kidney, eyes, nervous system, gastrointestinal tract and heart, and, finally,&#xD;
      it increases the morbidity and mortality of affected patients. This deposit in the myocardium&#xD;
      is manifested syndromically as heart failure with preserved or slightly reduced systolic&#xD;
      function, and important diastolic dysfunction. The analysis of diastolic function comprises&#xD;
      two components: the assessment of active relaxation, dependent on preload and afterload, and&#xD;
      the assessment of the passive properties of the tissue - its hardness or rigidity. Myocardial&#xD;
      stiffness represents an important parameter for diagnosis and prognosis, but its evaluation&#xD;
      is not included in conventional echocardiography. Cardiac elastography has recently been&#xD;
      proposed as a non-invasive diagnostic modality to assess myocardial stiffness.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 3, 2020</start_date>
  <completion_date type="Anticipated">May 29, 2021</completion_date>
  <primary_completion_date type="Anticipated">January 31, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dyastolic miocardical elasticity</measure>
    <time_frame>Around 6 months</time_frame>
    <description>Diastolic myocardial elasticity could provide a more direct response to the constitution of the tissue and allow a simple, safe and diastolic function assessment and early initiation of specific treatment.</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Amyloidosis</condition>
  <arm_group>
    <arm_group_label>Amyloidosis transthyretin with cardiac commitment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Shear wave elastography (SWE) will be used to evaluate to assess miocardial elasticity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Amyloidosis transthyretin without cardiac commitment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Shear wave elastography (SWE) will be used to evaluate to assess miocardial elasticity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy subjects</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Shear wave elastography (SWE) will be used to evaluate to assess miocardial elasticity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Shear wave elastography</intervention_name>
    <description>The elastographic technique by ultrasound (USE), shear waves or shear wave elastography (SWE), quantitatively evaluates tissue stiffness by mapping the propagation of acoustic waves (shear waves), in a non-invasive manner and without emission of ionizing radiation. Their speeds are tracked by the ultrasound equipment after tissue deformation occurs, generated by pulses of acoustic radiation (ARFI) of the transducer itself. Assuming the correlation between tissue stiffness and increased acoustic propagation speeds, it is possible to describe mathematically the elasticity of tissues by measuring specific acoustic waves.</description>
    <arm_group_label>Amyloidosis transthyretin with cardiac commitment</arm_group_label>
    <arm_group_label>Amyloidosis transthyretin without cardiac commitment</arm_group_label>
    <arm_group_label>Healthy subjects</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Documented diagnosis of HRTR with and without cardiac involvement.&#xD;
&#xD;
          -  For the definition of cardiac involvement by ATTRh, all the criteria below must be&#xD;
             presented:&#xD;
&#xD;
               -  Pathogenic mutation of TTR consistent with ATTRh.&#xD;
&#xD;
               -  Evidence of cardiac commitment by echocardiography or nuclear magnetic resonance&#xD;
                  with measurement of the interventricular septum at the end of diastole (SIVd)&gt;&#xD;
                  12mm or / and medical history of heart failure, and / or levels of troponin and /&#xD;
                  or BNP above the reference value without another more likely cause.&#xD;
&#xD;
               -  Amyloid deposit in cardiac or extra-cardiac tissue (eg, abdominal fat aspirate,&#xD;
                  salivary gland, connective sheath of the median nerve) confirmed by congo red&#xD;
                  staining or presence of grade 2 or 3 myocardial scintigraphy (DPD-CT) of cardiac&#xD;
                  uptake, in cases where the presence of monoclonal gammopathy of undetermined&#xD;
                  significance (MGUS) was ruled out.&#xD;
&#xD;
               -  In the presence of MGUS, confirmation of the TTR protein in the tissue is&#xD;
                  necessary through immunohistochemistry (IHC) or mass spectrometry.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of another type of cardiomyopathy such as hypertension, valve or ischemic&#xD;
             heart disease (eg, previous myocardial infarction documented with myocardial necrosis&#xD;
             markers and electrocardiographic changes).&#xD;
&#xD;
          -  Presence of diseases other than cardiac amyloidosis, impairing the assessment of&#xD;
             functional capacity, such as chronic obstructive pulmonary disease, severe arthritis&#xD;
             or peripheral arterial disease, recent or planned orthopedic procedure during the&#xD;
             course of the study (eg, spine surgery or under lower limbs) that impairs walking in&#xD;
             the 6-minute test evaluation.&#xD;
&#xD;
          -  Acute coronary heart disease or unstable angina in the past 3 months&#xD;
&#xD;
          -  Report of disease of the sinus or atrioventricular node with indication of a&#xD;
             pacemaker, but with no intention of implantation.&#xD;
&#xD;
          -  Presence of untreated hypothyroidism or hyperthyroidism.&#xD;
&#xD;
          -  Previous heart, liver or other organ transplant.&#xD;
&#xD;
          -  Presence of neoplasia in the last 3 years, except for basal and squamous cell&#xD;
             carcinomas of skin or cervical cancer in situ previously treated.&#xD;
&#xD;
          -  Presence of other medical conditions or comorbidities that, in the investigator's&#xD;
             opinion, could interfere with the course of the study or the interpretation of the&#xD;
             data.&#xD;
&#xD;
          -  Pregnancy.&#xD;
&#xD;
          -  History of alcohol abuse in the last 2 years or excessive daily alcohol intake (for&#xD;
             women, more than 14 units per week; for men, more than 21 units of alcohol per week&#xD;
             [unit: one glass of wine (125ml) = one dose of distillate = 332.5ml of beer).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of Sao Paulo Medical School - The Heart Institute</name>
      <address>
        <city>Sao Paulo</city>
        <zip>05403-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Fabio Fernandes, MD, PhD</last_name>
      <phone>+551126615057</phone>
      <email>fabio.fernandes@incor.usp.br</email>
    </contact>
    <contact_backup>
      <last_name>Aristoteles C. Neto, Bachelor</last_name>
      <phone>+5511960993262</phone>
      <email>aristotelesalencar@gmail.com</email>
    </contact_backup>
    <investigator>
      <last_name>Fabio Fernandes, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Aristoteles C. Neto, B.S.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Caio Cafezeiro, B.S.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Joao H. Rissato, B.S.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 29, 2020</study_first_submitted>
  <study_first_submitted_qc>June 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 2, 2020</study_first_posted>
  <last_update_submitted>June 29, 2020</last_update_submitted>
  <last_update_submitted_qc>June 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 2, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Sao Paulo General Hospital</investigator_affiliation>
    <investigator_full_name>Fábio Fernandes</investigator_full_name>
    <investigator_title>Full Professor</investigator_title>
  </responsible_party>
  <keyword>Amyloidosis</keyword>
  <keyword>Elastography</keyword>
  <keyword>Cardiac</keyword>
  <keyword>Miocardical stiffness</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amyloidosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT04456582
org study id: 4963/19/182
nct id: NCT04456582
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Amyloidosis by mutation of the transthyretin gene (ATTRh) is part of a group of diseases in
      which the deposit of structurally abnormal proteins (amyloid fibrils) affects multiple organs
      such as: liver, kidney, eyes, nervous system, gastrointestinal tract and heart, and, finally,
      it increases the morbidity and mortality of affected patients. This deposit in the myocardium
      is manifested syndromically as heart failure with preserved or slightly reduced systolic
      function, and important diastolic dysfunction. The analysis of diastolic function comprises
      two components: the assessment of active relaxation, dependent on preload and afterload, and
      the assessment of the passive properties of the tissue - its hardness or rigidity. Myocardial
      stiffness represents an important parameter for diagnosis and prognosis, but its evaluation
      is not included in conventional echocardiography. Cardiac elastography has recently been
      proposed as a non-invasive diagnostic modality to assess myocardial stiffness.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Dyastolic miocardical elasticity
time frame: Around 6 months
description: Diastolic myocardial elasticity could provide a more direct response to the constitution of the tissue and allow a simple, safe and diastolic function assessment and early initiation of specific treatment.
arm group label: Amyloidosis transthyretin with cardiac commitment
arm group type: Experimental
description: Shear wave elastography (SWE) will be used to evaluate to assess miocardial elasticity.
arm group label: Amyloidosis transthyretin without cardiac commitment
arm group type: Experimental
description: Shear wave elastography (SWE) will be used to evaluate to assess miocardial elasticity.
arm group label: Healthy subjects
arm group type: Placebo Comparator
description: Shear wave elastography (SWE) will be used to evaluate to assess miocardial elasticity.
intervention type: Procedure
intervention name: Shear wave elastography
description: The elastographic technique by ultrasound (USE), shear waves or shear wave elastography (SWE), quantitatively evaluates tissue stiffness by mapping the propagation of acoustic waves (shear waves), in a non-invasive manner and without emission of ionizing radiation. Their speeds are tracked by the ultrasound equipment after tissue deformation occurs, generated by pulses of acoustic radiation (ARFI) of the transducer itself. Assuming the correlation between tissue stiffness and increased acoustic propagation speeds, it is possible to describe mathematically the elasticity of tissues by measuring specific acoustic waves.
arm group label: Amyloidosis transthyretin with cardiac commitment
arm group label: Amyloidosis transthyretin without cardiac commitment
arm group label: Healthy subjects
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
investigator: 
country: Brazil
responsible party type: Sponsor-Investigator
investigator affiliation: University of Sao Paulo General Hospital
investigator full name: Fábio Fernandes
investigator title: Full Professor
mesh term: Amyloidosis
sharing ipd: No