<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/NCT03268135</url>
  </required_header>
  <id_info>
    <org_study_id>RNA-HF-AS</org_study_id>
    <nct_id>NCT03268135</nct_id>
  </id_info>
  <brief_title>Heart Failure and Aortic Stenosis Transcriptome</brief_title>
  <acronym>RNA-HF-AS</acronym>
  <official_title>Study of the Transcriptomic Alterations in Heart Failure and Aortic Stenosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>IRCCS Policlinico S. Donato</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ospedale San Raffaele</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>IRCCS Policlinico S. Donato</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 study is aimed to investigate the global transcriptome in order to determine the&#xD;
      expression profile of messenger RNAs (mRNAs), as well as long noncoding- (lncRNAs) and micro&#xD;
      noncoding-RNAs (miRNAs) in heart failure (HF) and in aortic stenosis (AS). The aim is to&#xD;
      clarify their role in cardiac disease pathogenesis, as well as their potential as biomarkers.&#xD;
      To this purpose, both tissue and blood specimens will be collected and patients will be&#xD;
      compared to individuals not affected by cardiovascular diseases.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators will collect plasma and cardiac tissue specimens from consenting subjects.&#xD;
      The investigators will evaluate the expression of mRNAs, miRNAs and lncRNAs in patients&#xD;
      affected by both end-stage and not end-stage HF as well as in patients affected by aortic&#xD;
      stenosis and undergoing valve replacement and requiring cardiac myectomy. The tissue&#xD;
      dysregulated RNAs will be next measured in plasma samples in order to clarify their potential&#xD;
      as biomarkers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 30, 2016</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">March 30, 2023</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Cardiac tissutal mRNAs signatures</measure>
    <time_frame>from Year 1 to Year 3</time_frame>
    <description>The mRNAs cardiac tissutal signatures of non- and end-stage heart failure patients and of aortic stenosis patients compared to controls</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cardiac tissutal miRNAs signatures</measure>
    <time_frame>from Year 1 to Year 3</time_frame>
    <description>The miRNAs cardiac tissutal signatures of non- and end-stage heart failure patients and of aortic stenosis patients compared to controls</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cardiac tissutal lncRNAs signatures</measure>
    <time_frame>from Year 1 to Year 3</time_frame>
    <description>The lncRNAs cardiac tissutal signatures of non- and end-stage heart failure patients and of aortic stenosis patients compared to controls</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Non end-stage, end-stage heart failure, aortic stenosis mRNAs signatures in plasmas</measure>
    <time_frame>from Year 3 to Year 5</time_frame>
    <description>The mRNAs dysregulated in cardiac tissues will be measured in blood plasma samples of non- and end-stage heart failure patients and of aortic stenosis patients compared to controls</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Non end-stage, end-stage heart failure, aortic stenosis miRNAs signatures in plasmas</measure>
    <time_frame>from Year 3 to Year 5</time_frame>
    <description>The miRNAs dysregulated in cardiac tissues will be measured in blood plasma samples of non- and end-stage heart failure patients and of aortic stenosis patients compared to controls</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Non end-stage, end-stage heart failure, aortic stenosis lncRNAs signatures in plasmas</measure>
    <time_frame>from Year 3 to Year 5</time_frame>
    <description>The lncRNAs dysregulated in cardiac tissues will be measured in blood plasma samples of non- and end-stage heart failure patients and of aortic stenosis patients compared to controls</description>
  </secondary_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Anticipated">500</enrollment>
  <condition>Heart Failure</condition>
  <condition>Aortic Stenosis</condition>
  <arm_group>
    <arm_group_label>Non end-stage heart failure</arm_group_label>
    <description>Measurement of RNAs in non end-stage heart failure patients undergoing to left ventricle reconstruction</description>
  </arm_group>
  <arm_group>
    <arm_group_label>End-stage heart failure</arm_group_label>
    <description>Measurement of RNAs in end-stage heart failure patients undergoing to left ventricular assisted device (LVAD)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Aortic Stenosis</arm_group_label>
    <description>Measurement of RNAs in patients affected by cardiac hypertrophy leading to aortic stenosis and requiring cardiac myectomy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Controls</arm_group_label>
    <description>Measurement of RNAs in individuals not affected by cardiovascular diseases</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>measurement of RNAs</intervention_name>
    <arm_group_label>Aortic Stenosis</arm_group_label>
    <arm_group_label>Controls</arm_group_label>
    <arm_group_label>End-stage heart failure</arm_group_label>
    <arm_group_label>Non end-stage heart failure</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      cardiac tissue and blood samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Cardiac surgery patients&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Non end-stage heart failure&#xD;
&#xD;
               -  left ventricle restoration surgery (SVR)&#xD;
&#xD;
               -  End Systolic Volume Index (ESVI) &gt;35 ml/m2&#xD;
&#xD;
               -  Ejection Fraction (EF)&lt;40%&#xD;
&#xD;
               -  previous transmural anterior myocardial infarction (MI)&#xD;
&#xD;
               -  age: 40-75&#xD;
&#xD;
          2. End-stage heart failure&#xD;
&#xD;
               -  left ventricle assisted device (LVAD) surgery&#xD;
&#xD;
               -  age: 40-75&#xD;
&#xD;
               -  Ejection Fraction (EF) &lt;25%&#xD;
&#xD;
               -  End Systolic Volume Index (ESVI)≥60 ml/m2&#xD;
&#xD;
          3. Aortic Stenosis&#xD;
&#xD;
               -  aortic valve replacement&#xD;
&#xD;
               -  intracardial pressure difference &gt;40 mmHg&#xD;
&#xD;
               -  septal diameter ≥1.3 cm&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Non end-stage heart failure&#xD;
&#xD;
               -  End Systolic Volume Index (ESVI)&lt;35 ml/m2&#xD;
&#xD;
               -  Ejection Fraction (EF)&gt;40%&#xD;
&#xD;
               -  Time from MI unknown&#xD;
&#xD;
               -  Pregnancy&#xD;
&#xD;
               -  Other genetic diseases&#xD;
&#xD;
               -  Neoplasms&#xD;
&#xD;
               -  Collagenopathies&#xD;
&#xD;
               -  Chemo/radiotherapy&#xD;
&#xD;
               -  Prolonged use of corticosteroids&#xD;
&#xD;
               -  Infections&#xD;
&#xD;
               -  Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) (not vaccination) and&#xD;
                  Hepatitis C Virus (HCV) positive&#xD;
&#xD;
          2. End-stage heart failure&#xD;
&#xD;
               -  EF&gt;25%&#xD;
&#xD;
               -  Time from MI unknown&#xD;
&#xD;
               -  Pregnancy&#xD;
&#xD;
               -  Other genetic diseases&#xD;
&#xD;
               -  Neoplasms&#xD;
&#xD;
               -  Collagenopathies&#xD;
&#xD;
               -  Chemo/radiotherapy&#xD;
&#xD;
               -  Prolonged use of corticosteroids&#xD;
&#xD;
               -  Infections&#xD;
&#xD;
               -  Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) (not vaccination) and&#xD;
                  Hepatitis C Virus (HCV) positive&#xD;
&#xD;
          3. Aortic Stenosis&#xD;
&#xD;
               -  coronaropathies&#xD;
&#xD;
               -  Pregnancy&#xD;
&#xD;
               -  Other genetic diseases&#xD;
&#xD;
               -  Neoplasms&#xD;
&#xD;
               -  Collagenopathies&#xD;
&#xD;
               -  Chemo/radiotherapy&#xD;
&#xD;
               -  Prolonged use of corticosteroids&#xD;
&#xD;
               -  Infections&#xD;
&#xD;
               -  Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) (not vaccination) and&#xD;
                  Hepatitis C Virus (HCV) positive&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Fabio Martelli, Dr</last_name>
    <role>Principal Investigator</role>
    <affiliation>IRCCS Policlinico S. Donato</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Fabio Martelli, Dr</last_name>
    <phone>+39 02 26437762</phone>
    <email>fabio.martelli@grupposandonato.it</email>
  </overall_contact>
  <location>
    <facility>
      <name>Irccs Policlinico San Donato</name>
      <address>
        <city>San Donato Milanese</city>
        <state>Milan</state>
        <zip>20097</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>FABIO MARTELLI, PhD</last_name>
      <phone>0252774683</phone>
      <email>fabio.martelli@grupposandonato.it</email>
    </contact>
    <investigator>
      <last_name>LORENZO MENICANTI, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>SIMONA GRECO, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>SERENELLA CASTELVECCHIO, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ospedale San Raffaele</name>
      <address>
        <city>Milano</city>
        <zip>20132</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michele De Bonis, MD, PhD</last_name>
      <email>debonis.michele@hsr.it</email>
    </contact>
    <investigator>
      <last_name>MICHELE DE BONIS, MD FESC FAHA</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>July 17, 2017</study_first_submitted>
  <study_first_submitted_qc>August 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 31, 2017</study_first_posted>
  <last_update_submitted>February 28, 2023</last_update_submitted>
  <last_update_submitted_qc>February 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 2, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>IRCCS Policlinico S. Donato</investigator_affiliation>
    <investigator_full_name>Fabio Martelli</investigator_full_name>
    <investigator_title>Dr, PhD, Molecular Cardiology Laboratory Director</investigator_title>
  </responsible_party>
  <keyword>miRNA</keyword>
  <keyword>lncRNAs</keyword>
  <keyword>transcriptome</keyword>
  <keyword>heart failure</keyword>
  <keyword>aortic stenosis</keyword>
  <keyword>biomarkers</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>
  <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/NCT03268135
org study id: RNA-HF-AS
nct id: NCT03268135
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study is aimed to investigate the global transcriptome in order to determine the
      expression profile of messenger RNAs (mRNAs), as well as long noncoding- (lncRNAs) and micro
      noncoding-RNAs (miRNAs) in heart failure (HF) and in aortic stenosis (AS). The aim is to
      clarify their role in cardiac disease pathogenesis, as well as their potential as biomarkers.
      To this purpose, both tissue and blood specimens will be collected and patients will be
      compared to individuals not affected by cardiovascular diseases.
The investigators will collect plasma and cardiac tissue specimens from consenting subjects.
      The investigators will evaluate the expression of mRNAs, miRNAs and lncRNAs in patients
      affected by both end-stage and not end-stage HF as well as in patients affected by aortic
      stenosis and undergoing valve replacement and requiring cardiac myectomy. The tissue
      dysregulated RNAs will be next measured in plasma samples in order to clarify their potential
      as biomarkers.
observational model: Case-Control
time perspective: Retrospective
measure: Cardiac tissutal mRNAs signatures
time frame: from Year 1 to Year 3
description: The mRNAs cardiac tissutal signatures of non- and end-stage heart failure patients and of aortic stenosis patients compared to controls
measure: Cardiac tissutal miRNAs signatures
time frame: from Year 1 to Year 3
description: The miRNAs cardiac tissutal signatures of non- and end-stage heart failure patients and of aortic stenosis patients compared to controls
measure: Cardiac tissutal lncRNAs signatures
time frame: from Year 1 to Year 3
description: The lncRNAs cardiac tissutal signatures of non- and end-stage heart failure patients and of aortic stenosis patients compared to controls
measure: Non end-stage, end-stage heart failure, aortic stenosis mRNAs signatures in plasmas
time frame: from Year 3 to Year 5
description: The mRNAs dysregulated in cardiac tissues will be measured in blood plasma samples of non- and end-stage heart failure patients and of aortic stenosis patients compared to controls
measure: Non end-stage, end-stage heart failure, aortic stenosis miRNAs signatures in plasmas
time frame: from Year 3 to Year 5
description: The miRNAs dysregulated in cardiac tissues will be measured in blood plasma samples of non- and end-stage heart failure patients and of aortic stenosis patients compared to controls
measure: Non end-stage, end-stage heart failure, aortic stenosis lncRNAs signatures in plasmas
time frame: from Year 3 to Year 5
description: The lncRNAs dysregulated in cardiac tissues will be measured in blood plasma samples of non- and end-stage heart failure patients and of aortic stenosis patients compared to controls
arm group label: Non end-stage heart failure
description: Measurement of RNAs in non end-stage heart failure patients undergoing to left ventricle reconstruction
arm group label: End-stage heart failure
description: Measurement of RNAs in end-stage heart failure patients undergoing to left ventricular assisted device (LVAD)
arm group label: Aortic Stenosis
description: Measurement of RNAs in patients affected by cardiac hypertrophy leading to aortic stenosis and requiring cardiac myectomy
arm group label: Controls
description: Measurement of RNAs in individuals not affected by cardiovascular diseases
intervention type: Diagnostic Test
intervention name: measurement of RNAs
arm group label: Aortic Stenosis
arm group label: Controls
arm group label: End-stage heart failure
arm group label: Non end-stage heart failure
cardiac tissue and blood samples
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 40 Years
maximum age: 75 Years
healthy volunteers: No
last name: Fabio Martelli, Dr
role: Principal Investigator
affiliation: IRCCS Policlinico S. Donato
last name: Fabio Martelli, Dr
phone: +39 02 26437762
email: fabio.martelli@grupposandonato.it
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: IRCCS Policlinico S. Donato
investigator full name: Fabio Martelli
investigator title: Dr, PhD, Molecular Cardiology Laboratory Director
mesh term: Heart Failure
mesh term: Aortic Valve Stenosis
mesh term: Constriction, Pathologic
sharing ipd: No