<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/NCT04406805</url>
  </required_header>
  <id_info>
    <org_study_id>KB/211/2018</org_study_id>
    <nct_id>NCT04406805</nct_id>
  </id_info>
  <brief_title>TMAO in Patients With Severe Aortic Stenosis</brief_title>
  <acronym>TASTE</acronym>
  <official_title>Concentration of Trimethylamine-N-oxide Versus Echocardiographic, Biochemical and Histopathological Parameters of Heart Failure in Patients With Severe Aortic Stenosis: a Prospective, Observatory Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Warsaw</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of Warsaw</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>
      Trimethylamine N-oxide (TMAO) has recently gained increasing scientific interest in the field&#xD;
      of cardiovascular disease, including its role in cell protection against osmotic and&#xD;
      hydrostatic stress. Aortic stenosis (AS) is the most common valvular heart disease, affecting&#xD;
      about 7.6 million people over 75 years of age in North America and Europe alone. We&#xD;
      hypothesized that TMAO plays a role in protection of the cardiomyocytes against pressure&#xD;
      overload in patients with AS. The primary aim of this study is to assess the correlation&#xD;
      between the serum and urine TMAO concentration, and (i) echocardiographic, (ii) biochemical&#xD;
      and (iii) histopathological parameters of heart failure in patients with severe AS. The&#xD;
      secondary aim of this study is to evaluate a correlation between the baseline TMAO&#xD;
      concentrations and the post-treatment clinical status, as well as the post-treatment&#xD;
      echocardiographic and biochemical parameters.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 15, 2019</start_date>
  <completion_date type="Anticipated">February 15, 2023</completion_date>
  <primary_completion_date type="Anticipated">February 15, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Correlation between the serum and urine trimethylamine N-oxide concentration and aortic valve area index</measure>
    <time_frame>January 15, 2019 - February 15, 2023</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Correlation between the serum and urine trimethylamine N-oxide concentration and (i) other echocardiographic, (ii) biochemical and (iii) histopathological parameters of heart failure.</measure>
    <time_frame>January 15, 2019 - February 15, 2023</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between the baseline trimethylamine N-oxide concentrations and the post-treatment clinical status, as well as the post-treatment echocardiographic and biochemical parameters.</measure>
    <time_frame>January 15, 2019 - February 15, 2023</time_frame>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">70</enrollment>
  <condition>Aortic Stenosis</condition>
  <condition>Heart Failure</condition>
  <arm_group>
    <arm_group_label>Severe aortic stenosis</arm_group_label>
    <description>Patients will be enrolled among those who will be (i) aged from 18 to 99 years, (ii) admitted to the hospital due to severe aortic stenosis, and (iii) qualified for treatment with either surgical aortic valve replacement or transcatheter aortic valve implantation</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Measurement of plasma and urine trimethylamine-N-oxide concentration</intervention_name>
    <description>Information already included in arm/group descriptions.</description>
    <arm_group_label>Severe aortic stenosis</arm_group_label>
    <other_name>N-terminal pro-brain natriuretic peptide measurement, echocardiography, biopsy of a myocardium in patients undergoing surgical aortic valve replacement</other_name>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Plasma and urine samples for trimethylamine-N-oxide analysis with a ultra performance liquid&#xD;
      chromatograph coupled with a mass spectrometer&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients will be enrolled among those who will be (i) aged from 18 to 99 years, (ii)&#xD;
        admitted to the 1st Chair and Department of Cardiology or Department of Cardiosurgery,&#xD;
        Medical University of Warsaw due to severe AS, and (iii) qualified for treatment with&#xD;
        either surgical aortic valve replacement or transcatheter aortic valve implantation.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Informed consent to participate in the study&#xD;
&#xD;
          -  Severe aortic stenosis, defined as aortic valve area &lt;1.0 cm2 or aortic valve area&#xD;
             index &lt;0.6 cm2/m2 as calculated by the continuity equation on transthoracic&#xD;
             echocardiography, regardless of the transvalvular gradient, with or without coexisting&#xD;
             symptoms of heart failure&#xD;
&#xD;
          -  Qualification for surgical aortic valve replacement or transcatheter aortic valve&#xD;
             implantation by the Heart Team in accordance with European Society of Cardiology&#xD;
             guidelines&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Heart failure of etiology other than aortic stenosis&#xD;
&#xD;
          -  Coexisting, haemodynamically significant aortic regurgitation&#xD;
&#xD;
          -  Myocardial infarction within the last 3 months&#xD;
&#xD;
          -  Coronary revascularization within the last month or planned during transcatheter&#xD;
             aortic valve implantation or surgical aortic valve replacement&#xD;
&#xD;
          -  Chronic kidney disease with estimated glomerular filtration rate &lt;45 ml/min/1.73 m2&#xD;
&#xD;
          -  Acute gastrointestinal disease within the last month&#xD;
&#xD;
          -  Active neoplastic disease&#xD;
&#xD;
          -  Chronic inflammatory disease&#xD;
&#xD;
          -  Autoimmune disease&#xD;
&#xD;
          -  Chronic intestinal disease&#xD;
&#xD;
          -  Antibiotic therapy within the last 2 months&#xD;
&#xD;
          -  Dietary supplements within the last 7 days&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
  </eligibility>
  <overall_contact>
    <last_name>Aleksandra Gąsecka, MD</last_name>
    <phone>+48225991951</phone>
    <email>gaseckaa@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>1st Chair and Department of Cardiology and Department of Cardiosurgery, Medical University of Warsaw</name>
      <address>
        <city>Warsaw</city>
        <state>Masovia</state>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Aleksandra Gąsecka, PhD</last_name>
      <phone>+48225991951</phone>
      <email>gaseckaa@gmail.com</email>
    </contact>
    <investigator>
      <last_name>Agnieszka Kapłon-Cieślicka, Ass. Prof.</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Aleksandra Gasecka, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Michał Konwerski, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Marcin Ufnal, Prof.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Radosław Wilimski, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Paweł Czub, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Monika Budnik, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Poland</country>
  </location_countries>
  <results_reference>
    <citation>Jaworska K, Hering D, Mosieniak G, Bielak-Zmijewska A, Pilz M, Konwerski M, Gasecka A, Kaplon-Cieslicka A, Filipiak K, Sikora E, Holyst R, Ufnal M. TMA, A Forgotten Uremic Toxin, but Not TMAO, Is Involved in Cardiovascular Pathology. Toxins (Basel). 2019 Aug 26;11(9):490. doi: 10.3390/toxins11090490.</citation>
    <PMID>31454905</PMID>
  </results_reference>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>May 22, 2020</study_first_submitted>
  <study_first_submitted_qc>May 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 28, 2020</study_first_posted>
  <last_update_submitted>June 3, 2020</last_update_submitted>
  <last_update_submitted_qc>June 3, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 5, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Aortic Stenosis</keyword>
  <keyword>Heart Failure</keyword>
  <keyword>Trimethylamine</keyword>
  <keyword>TMAO</keyword>
  <keyword>Bacterial Metabolites</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
    <mesh_term>Aortic Valve Stenosis</mesh_term>
    <mesh_term>Constriction, Pathologic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Natriuretic Peptide, Brain</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>The individual participant shared only in case the identity of the participant has been made unrecognizable.</ipd_description>
  </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/NCT04406805
org study id: KB/211/2018
nct id: NCT04406805
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Trimethylamine N-oxide (TMAO) has recently gained increasing scientific interest in the field
      of cardiovascular disease, including its role in cell protection against osmotic and
      hydrostatic stress. Aortic stenosis (AS) is the most common valvular heart disease, affecting
      about 7.6 million people over 75 years of age in North America and Europe alone. We
      hypothesized that TMAO plays a role in protection of the cardiomyocytes against pressure
      overload in patients with AS. The primary aim of this study is to assess the correlation
      between the serum and urine TMAO concentration, and (i) echocardiographic, (ii) biochemical
      and (iii) histopathological parameters of heart failure in patients with severe AS. The
      secondary aim of this study is to evaluate a correlation between the baseline TMAO
      concentrations and the post-treatment clinical status, as well as the post-treatment
      echocardiographic and biochemical parameters.
observational model: Cohort
time perspective: Prospective
measure: Correlation between the serum and urine trimethylamine N-oxide concentration and aortic valve area index
time frame: January 15, 2019 - February 15, 2023
measure: Correlation between the serum and urine trimethylamine N-oxide concentration and (i) other echocardiographic, (ii) biochemical and (iii) histopathological parameters of heart failure.
time frame: January 15, 2019 - February 15, 2023
measure: Correlation between the baseline trimethylamine N-oxide concentrations and the post-treatment clinical status, as well as the post-treatment echocardiographic and biochemical parameters.
time frame: January 15, 2019 - February 15, 2023
arm group label: Severe aortic stenosis
description: Patients will be enrolled among those who will be (i) aged from 18 to 99 years, (ii) admitted to the hospital due to severe aortic stenosis, and (iii) qualified for treatment with either surgical aortic valve replacement or transcatheter aortic valve implantation
intervention type: Diagnostic Test
intervention name: Measurement of plasma and urine trimethylamine-N-oxide concentration
description: Information already included in arm/group descriptions.
arm group label: Severe aortic stenosis
other name: N-terminal pro-brain natriuretic peptide measurement, echocardiography, biopsy of a myocardium in patients undergoing surgical aortic valve replacement
Plasma and urine samples for trimethylamine-N-oxide analysis with a ultra performance liquid
      chromatograph coupled with a mass spectrometer
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
last name: Aleksandra Gąsecka, MD
phone: +48225991951
email: gaseckaa@gmail.com
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: Poland
citation: Jaworska K, Hering D, Mosieniak G, Bielak-Zmijewska A, Pilz M, Konwerski M, Gasecka A, Kaplon-Cieslicka A, Filipiak K, Sikora E, Holyst R, Ufnal M. TMA, A Forgotten Uremic Toxin, but Not TMAO, Is Involved in Cardiovascular Pathology. Toxins (Basel). 2019 Aug 26;11(9):490. doi: 10.3390/toxins11090490.
PMID: 31454905
responsible party type: Sponsor
mesh term: Heart Failure
mesh term: Aortic Valve Stenosis
mesh term: Constriction, Pathologic
mesh term: Natriuretic Peptide, Brain
sharing ipd: Undecided
ipd description: The individual participant shared only in case the identity of the participant has been made unrecognizable.