<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/NCT03819283</url>
  </required_header>
  <id_info>
    <org_study_id>APHP180013</org_study_id>
    <secondary_id>2018-A01752-53</secondary_id>
    <nct_id>NCT03819283</nct_id>
  </id_info>
  <brief_title>NASH and Coronary Disease</brief_title>
  <acronym>CORO-NASH</acronym>
  <official_title>Prevalence and Impact of NAFLD in Patients With Symptomatic Coronary Artery Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Institute of Cardiometabolism and Nutrition, France</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</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>
      Although the clinical relationship between NAFLD/NASH and cardiovascular (CV) risk is now&#xD;
      well established, there is very little awareness of the hepatic disease and the way it may&#xD;
      contribute to increased CV risk in patients seen in cardiology clinics for complications of&#xD;
      coronary artery disease. Our clinical hypothesis is that NAFLD, possibly at a stage of&#xD;
      advanced fibrosis, is common in patients with symptomatic coronary artery disease (CAD) and&#xD;
      increases the risk of severe atherosclerotic lesions. The primary aim of this study is to&#xD;
      determine (a) the prevalence and (b) the severity spectrum of NAFLD among patients with&#xD;
      symptomatic coronary artery disease. The secondary aims are: to analyze the impact of the&#xD;
      presence and the severity spectrum of NAFLD (steatosis, steatohepatitis and fibrosis) on the&#xD;
      severity of CAD ; To determine the profile of NAFLD patients at risk to develop coronary&#xD;
      lesions; To explore the mechanistic link between NAFLD and CAD beyond common metabolic risk&#xD;
      factors.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Because of shared metabolic risk factors and pathogenic pathways (insulin resistance, chronic&#xD;
      low grade inflammation, atherogenic dyslipidemia) non-alcoholic fatty liver disease is&#xD;
      frequently associated with cardiovascular (CV) disease. Despite a lot of transversal studies&#xD;
      showing a frequent association between NAFLD and CV disease, it is difficult to determine if&#xD;
      NAFLD plays an active role in atherogenesis or is just a marker of common risk factors. Some&#xD;
      longitudinal studies, although retrospectives, showed that NAFLD favors the progression of&#xD;
      early atherosclerosis, suggesting that NAFLD is an independent CV risk factor beyond the&#xD;
      association driven by metabolic syndrome.&#xD;
&#xD;
      Although the clinical relationship between NAFLD/NASH and CV risk is now well established,&#xD;
      there is very little awareness of the hepatic disease and the way it may contribute to&#xD;
      increased CV risk in patients seen in cardiology clinics for complications of coronary artery&#xD;
      disease (CAD). Our clinical hypothesis is that NAFLD, possibly at a stage of advanced&#xD;
      fibrosis, is common in patients with symptomatic CAD and increases the risk of severe&#xD;
      atherosclerotic lesions.&#xD;
&#xD;
      The primary aim of this study is to determine (a) the prevalence of NAFLD among patients with&#xD;
      symptomatic CAD.&#xD;
&#xD;
      The secondary aims are:&#xD;
&#xD;
        -  To determine the severity spectrum of NAFLD among patients with coronary artery disease.&#xD;
&#xD;
        -  To analyze the impact of the presence and the severity spectrum of NAFLD (steatosis,&#xD;
           steatohepatitis and fibrosis) on the severity of CAD and long term clinical outcomes&#xD;
           (ancillary studies)&#xD;
&#xD;
        -  To determine the clinical profile of NAFLD patients at risk to develop coronary lesions&#xD;
&#xD;
        -  To explore the mechanistic link between NAFLD and CAD beyond common metabolic risk&#xD;
           factors.&#xD;
&#xD;
        -  Establish a cohort of patients with NAFLD and coronary disease allowing future&#xD;
           subsequent ancillary studies.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 19, 2019</start_date>
  <completion_date type="Anticipated">July 19, 2024</completion_date>
  <primary_completion_date type="Anticipated">July 19, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>NAFLD and significant fibrosis (≥ F2)</measure>
    <time_frame>Visit 2</time_frame>
    <description>NAFLD will be defined by the presence of steatosis at ultrasound concomitant with at least one metabolic risk factor among overweight/obesity, type 2 diabetes, dyslipidemia. The severity of NAFLD will be determined by the presence of significant fibrosis (≥F2) by noninvasive measures (either serum markers or transient elastography).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Severity of the coronary lesions</measure>
    <time_frame>Visit 1</time_frame>
    <description>Based on the results of the coronary angiography, patients will be classified according to the severity of CAD as follows: no CAD, stable CAD (less than 50% stenosis, 1 vessel CAD with &gt; 50% stenosis, 2 vessels CAD with &gt; 50% stenosis, 3 vessels CAD with &gt; 50% stenosis), and acute coronary syndrome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between the histological severity of NAFLD and the severity of coronary lesions</measure>
    <time_frame>51 months after the start of the study</time_frame>
    <description>The severity of the coronary lesions will be defined as follows : absent, stable coronary lesions (significant &gt;=50% or non significant coronary atheroma), acute coronary syndrome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Analyse of clinical factors associated with the severity of coronary lesions according to the presence or absence of NAFLD</measure>
    <time_frame>51 months after the start of the study</time_frame>
    <description>The severity of the coronary lesions will be defined as follows : absent, stable coronary lesions (significant &gt;= 50% or non significant coronary atheroma), acute coronary syndrome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Analyse of the metabolomic signature associated with the severity of coronary lesions according to the presence and severity of NAFLD</measure>
    <time_frame>Visit 1 and 2</time_frame>
    <description>The severity of the coronary lesions will be defined as follows : absent, stable coronary lesions (significant &gt;=50%or non significant coronary atheroma), acute coronary syndrome</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">260</enrollment>
  <condition>Non-Alcoholic Fatty Liver Disease</condition>
  <arm_group>
    <arm_group_label>Hepatic evaluation</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Hepatic evaluation</intervention_name>
    <description>Evaluation of hepatic steatosis and fibrosis by non invasive tests, either serum markers (steatotest, Fibrotest) or imaging methods (CAP, FibroScan)</description>
    <arm_group_label>Hepatic evaluation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients (&gt;18 years old) that undergo coronary angiography for suspected CAD&#xD;
             for: acute coronary syndrome (ACS) with ST-elevation ACS (STE-ACS) or non-ST elevation&#xD;
             (NSTE-ACS) with or without troponin elevation OR suspicion of stable coronary artery&#xD;
             disease after stress imaging techniques and/or symptoms of angina.&#xD;
&#xD;
          -  Patients with one or more of traditional cardiovascular risk factors.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients unable to sign the informed consent&#xD;
&#xD;
          -  Morbidly obese patients (BMI &gt; 40kg/m2)&#xD;
&#xD;
          -  Excessive alcohol consumption of more than 50 g/day&#xD;
&#xD;
          -  Patients with known other causes of chronic liver disease (viral hepatitis,&#xD;
             autoimmune, hemochromatosis...)&#xD;
&#xD;
          -  Active neoplastic pathology&#xD;
&#xD;
          -  Pregnant or breastfeeding women&#xD;
&#xD;
          -  Protected adults&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Gérard HELFT, PU-PH</last_name>
    <phone>0142162911</phone>
    <email>gerard.helft@aphp.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Pitié Salpêtrière Hospital</name>
      <address>
        <city>Paris</city>
        <zip>75013</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>January 10, 2019</study_first_submitted>
  <study_first_submitted_qc>January 25, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <last_update_submitted>September 5, 2022</last_update_submitted>
  <last_update_submitted_qc>September 5, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>fatty liver, coronary artery disease, atherosclerosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Diseases</mesh_term>
    <mesh_term>Fatty Liver</mesh_term>
    <mesh_term>Non-alcoholic Fatty Liver Disease</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/NCT03819283
org study id: APHP180013
secondary id: 2018-A01752-53
nct id: NCT03819283
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Although the clinical relationship between NAFLD/NASH and cardiovascular (CV) risk is now
      well established, there is very little awareness of the hepatic disease and the way it may
      contribute to increased CV risk in patients seen in cardiology clinics for complications of
      coronary artery disease. Our clinical hypothesis is that NAFLD, possibly at a stage of
      advanced fibrosis, is common in patients with symptomatic coronary artery disease (CAD) and
      increases the risk of severe atherosclerotic lesions. The primary aim of this study is to
      determine (a) the prevalence and (b) the severity spectrum of NAFLD among patients with
      symptomatic coronary artery disease. The secondary aims are: to analyze the impact of the
      presence and the severity spectrum of NAFLD (steatosis, steatohepatitis and fibrosis) on the
      severity of CAD ; To determine the profile of NAFLD patients at risk to develop coronary
      lesions; To explore the mechanistic link between NAFLD and CAD beyond common metabolic risk
      factors.
Because of shared metabolic risk factors and pathogenic pathways (insulin resistance, chronic
      low grade inflammation, atherogenic dyslipidemia) non-alcoholic fatty liver disease is
      frequently associated with cardiovascular (CV) disease. Despite a lot of transversal studies
      showing a frequent association between NAFLD and CV disease, it is difficult to determine if
      NAFLD plays an active role in atherogenesis or is just a marker of common risk factors. Some
      longitudinal studies, although retrospectives, showed that NAFLD favors the progression of
      early atherosclerosis, suggesting that NAFLD is an independent CV risk factor beyond the
      association driven by metabolic syndrome.

      Although the clinical relationship between NAFLD/NASH and CV risk is now well established,
      there is very little awareness of the hepatic disease and the way it may contribute to
      increased CV risk in patients seen in cardiology clinics for complications of coronary artery
      disease (CAD). Our clinical hypothesis is that NAFLD, possibly at a stage of advanced
      fibrosis, is common in patients with symptomatic CAD and increases the risk of severe
      atherosclerotic lesions.

      The primary aim of this study is to determine (a) the prevalence of NAFLD among patients with
      symptomatic CAD.

      The secondary aims are:

        -  To determine the severity spectrum of NAFLD among patients with coronary artery disease.

        -  To analyze the impact of the presence and the severity spectrum of NAFLD (steatosis,
           steatohepatitis and fibrosis) on the severity of CAD and long term clinical outcomes
           (ancillary studies)

        -  To determine the clinical profile of NAFLD patients at risk to develop coronary lesions

        -  To explore the mechanistic link between NAFLD and CAD beyond common metabolic risk
           factors.

        -  Establish a cohort of patients with NAFLD and coronary disease allowing future
           subsequent ancillary studies.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: NAFLD and significant fibrosis (≥ F2)
time frame: Visit 2
description: NAFLD will be defined by the presence of steatosis at ultrasound concomitant with at least one metabolic risk factor among overweight/obesity, type 2 diabetes, dyslipidemia. The severity of NAFLD will be determined by the presence of significant fibrosis (≥F2) by noninvasive measures (either serum markers or transient elastography).
measure: Severity of the coronary lesions
time frame: Visit 1
description: Based on the results of the coronary angiography, patients will be classified according to the severity of CAD as follows: no CAD, stable CAD (less than 50% stenosis, 1 vessel CAD with > 50% stenosis, 2 vessels CAD with > 50% stenosis, 3 vessels CAD with > 50% stenosis), and acute coronary syndrome.
measure: Correlation between the histological severity of NAFLD and the severity of coronary lesions
time frame: 51 months after the start of the study
description: The severity of the coronary lesions will be defined as follows : absent, stable coronary lesions (significant >=50% or non significant coronary atheroma), acute coronary syndrome
measure: Analyse of clinical factors associated with the severity of coronary lesions according to the presence or absence of NAFLD
time frame: 51 months after the start of the study
description: The severity of the coronary lesions will be defined as follows : absent, stable coronary lesions (significant >= 50% or non significant coronary atheroma), acute coronary syndrome
measure: Analyse of the metabolomic signature associated with the severity of coronary lesions according to the presence and severity of NAFLD
time frame: Visit 1 and 2
description: The severity of the coronary lesions will be defined as follows : absent, stable coronary lesions (significant >=50%or non significant coronary atheroma), acute coronary syndrome
arm group label: Hepatic evaluation
arm group type: Other
intervention type: Diagnostic Test
intervention name: Hepatic evaluation
description: Evaluation of hepatic steatosis and fibrosis by non invasive tests, either serum markers (steatotest, Fibrotest) or imaging methods (CAP, FibroScan)
arm group label: Hepatic evaluation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gérard HELFT, PU-PH
phone: 0142162911
email: gerard.helft@aphp.fr
facility: 
status: Recruiting
country: France
responsible party type: Sponsor
mesh term: Liver Diseases
mesh term: Fatty Liver
mesh term: Non-alcoholic Fatty Liver Disease
sharing ipd: No