<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/NCT01695083</url>
  </required_header>
  <id_info>
    <org_study_id>P091119</org_study_id>
    <secondary_id>2011-A00829-32</secondary_id>
    <nct_id>NCT01695083</nct_id>
  </id_info>
  <brief_title>Non Invasive Measurements of Fibrosis, Inflammation and Steatohepatitis in Morbidly Obese Patients</brief_title>
  <acronym>FIRM</acronym>
  <official_title>Non Invasive Measurements of Fibrosis, Inflammation and Steatohepatitis in Morbidly Obese Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Abstract:&#xD;
&#xD;
      Fatty liver most frequently corresponds to a fat overload of the liver. It is usually&#xD;
      classified as alcoholic steatosis or non-alcoholic steatosis. In the case of non alcoholic&#xD;
      fatty liver overload, the histological spectrum ranges from simple steatosis to&#xD;
      steatohepatitis (NASH) which associates inflammation to steatosis, with a risk of progression&#xD;
      to fibrosis and cirrhosis. Obese patients are at particular risk of NASH. Screening of these&#xD;
      hepatic lesions is difficult especially as they may exist while the liver tests are normal.&#xD;
      The diagnosis of NASH is currently done by liver biopsy, which exposes them in particular to&#xD;
      the risk of hemorrhagic complications.&#xD;
&#xD;
      Number of subjects required:&#xD;
&#xD;
      According to the literature and data collected Louis Mourier in the recent years, the&#xD;
      inclusion of 200 patients would examine 20-40 patients with severe histological steatosis and&#xD;
      steatohepatitis. All patients will be included in Louis Mourier hospital.&#xD;
&#xD;
      Follow-up: one month Search duration: 37 months Duration inclusions: 36 months The total&#xD;
      duration of participation for a patient will be one month.&#xD;
&#xD;
      Methodology:&#xD;
&#xD;
      It is a monocentric, prospective study evaluating the value of noninvasive tests for the&#xD;
      diagnosis of hepatic lesions in morbid obese patients. The &quot;open &quot; MRI system allows access&#xD;
      to MRI for all obese patients (maximum weight 250 kg). Three of such systems are available in&#xD;
      France and liver pathology can be explored only on the system of Louis Mourier.&#xD;
&#xD;
      The reference method is liver histology; studied tests are abdominal MRI, Fibroscan / CAP,&#xD;
      and serum tests.&#xD;
&#xD;
      Examinations required specifically for research Examinations required specifically for the&#xD;
      research is abdominal MRI, FibroScan/ CAP and serum tests.&#xD;
&#xD;
      Primary endpoint :&#xD;
&#xD;
      To validate the use of abdominal MRI, the FibroScan/ CAP and serum tests for finding severe&#xD;
      steatosis and / or NASH, specificity, sensitivity, positive and negative predictive values of&#xD;
      these tests are calculated. The gold standard is the result of histology on liver biopsy,&#xD;
      with a morphometric study of these parameters. ROC curves are used to determine the best&#xD;
      compromise between sensitivity and specificity.&#xD;
&#xD;
      The secondary endpoints were:&#xD;
&#xD;
      Histological lesions of liver fibrosis. Quantification of abdominal fat by MRI (in the form&#xD;
      of three variables of interest: quantification of the surface of the visceral fat, of&#xD;
      subcutaneous fat and of intrahepatic fat assessed by the percentage loss of signal&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Main objective :&#xD;
&#xD;
      The main objective of the study was to determine in patients with morbid obesity waiting for&#xD;
      bariatric surgery, the accuracy of non-invasive tests for diagnosis of severe steatosis and /&#xD;
      or NASH.&#xD;
&#xD;
      The gold standard is liver biopsy with a morphometric study.&#xD;
&#xD;
      Non-invasive tests will be used:&#xD;
&#xD;
        -  Serum tests: the FibroMax (which includes the NASH test, FibroTest and SteatoTest) and&#xD;
           FibroMeter.&#xD;
&#xD;
        -  Radiological examinations: MRI and FibroScan / CAP&#xD;
&#xD;
      Secondary objectives :&#xD;
&#xD;
      The secondary objectives are:&#xD;
&#xD;
        1. to determine the accuracy of these non-invasive tests for the diagnosis of severe&#xD;
           steatosis alone, steatohepatitis (NASH or) and hepatic fibrosis&#xD;
&#xD;
        2. to determine the best combination of these tests to better evaluate the presence of&#xD;
           severe steatosis, NASH and a hepatic fibrosis.&#xD;
&#xD;
        3. to quantify MRI visceral and subcutaneous fat in morbidly obese patients&#xD;
&#xD;
      Research Design :&#xD;
&#xD;
        1. Judging Criteria&#xD;
&#xD;
           Primary endpoint To validate the use of serum tests, FibroScan / CAP abdominal MRI for&#xD;
           the diagnosis of severe steatosis and / or NASH (specificity, sensitivity, positive and&#xD;
           negative predictive values). The gold standard is the result of histology on liver&#xD;
           biopsy, with a morphometric study. For each diagnostic test, a ROC curve is used to&#xD;
           determine the best compromise between sensitivity and specificity.&#xD;
&#xD;
           The histological diagnosis of severe steatosis is defined by the presence of hepatic&#xD;
           steatosis grade 3 or higher. The diagnosis of NASH is defined by the presence of lobular&#xD;
           inflammation with neutrophils and hepatocytes ballooning.&#xD;
&#xD;
           Secondary endpoints&#xD;
&#xD;
           - Histological lesions of liver fibrosis Quantification of abdominal fat by MRI (in the&#xD;
           form of three variables of interest: quantification of the surface of the visceral fat&#xD;
           from the surface of the subcutaneous fat and the amount of intrahepatic fat assessed by&#xD;
           the percentage loss of signal).&#xD;
&#xD;
        2. Methodology and expected number of patients in research&#xD;
&#xD;
           This is a prospective study evaluating the value of noninvasive tests for the diagnosis&#xD;
           of hepatic lesions in morbid obese patients. The MRI system &quot;open&quot; allows access to&#xD;
           obese patients. Three such systems are available in France and liver pathology is&#xD;
           supported only on the system of Louis Mourier.&#xD;
&#xD;
           The reference method is liver histology; tests studied are MRI abdominal Fibroscan /&#xD;
           CAP, and serum tests (FibroTest, FibroMeter, SteatoTest, NASH test).&#xD;
&#xD;
           The study will be conducted in 200 obese patients who will have a liver biopsy performed&#xD;
           during bariatric surgery:&#xD;
&#xD;
             -  Tests for the detection of steatosis (fat quantification of intrahepatic MRI&#xD;
                measurement of steatosis by CAP, serum tests) and evaluating histological steatosis&#xD;
                (main objective)&#xD;
&#xD;
             -  Tests for the detection of NASH (test serum) and histology&#xD;
&#xD;
             -  Tests of fibrosis (serum tests; FibroScan) and histological data assessing&#xD;
                fibrosis.&#xD;
&#xD;
           The duration and extent of obesity (BMI) and biological data (HOMA-test) will be taken&#xD;
           into account.&#xD;
&#xD;
        3. Examinations required specifically for research&#xD;
&#xD;
           Liver biopsy is routinely performed intraoperatively in the routine monitoring of&#xD;
           patients for bariatric surgery, examinations specific to the research are:&#xD;
&#xD;
             -  Serum tests&#xD;
&#xD;
             -  FibroScan / CAP&#xD;
&#xD;
             -  Abdominal MRI&#xD;
&#xD;
           Risk / risk absences The sting at blood sampling can cause the formation of a small&#xD;
           hematoma without gravity, which will subside spontaneously within a few days.&#xD;
&#xD;
           FibroScan ® / CAP presents no risk of side effects. Liver MRI shows no risk if the&#xD;
           cons-indications are respected. Wearing a stack (pacemaker) or any element that contains&#xD;
           the iron near the eyes or head are contra-indications as are a major risk factor (risk&#xD;
           of death, blindness). The presence of a heart valve or a stent (also called metal&#xD;
           prosthesis) is not an absolute contra-indication-and their compatibility with MRI will&#xD;
           be verified before completion of the examination, as is the case in practice clinic ..&#xD;
&#xD;
           Liver biopsy, which is part of the examinations carried out in a systematic way without&#xD;
           any protocol adds no additional risk to the surgical&#xD;
&#xD;
        4. Study site&#xD;
&#xD;
           The study will be conducted at Louis Mourier, a reference center for the treatment of&#xD;
           obesity, which has an open system allowing access to obese.&#xD;
&#xD;
        5. Indications for bariatric surgery&#xD;
&#xD;
      Indications for bariatric surgery at Louis Mourier, a reference center for the treatment of&#xD;
      obesity, are consistent with the recommendations of the HAS in 2009, based on professional&#xD;
      consensus.&#xD;
&#xD;
      Surgery is indicated in patients with all of the following criteria:&#xD;
&#xD;
        1. BMI ≥ 40 or BMI ≥ 35 with comorbid&#xD;
&#xD;
        2. failure (s) prior (s) of the conventional treatment of obesity combined dietary,&#xD;
           physical activity and behavioral therapy&#xD;
&#xD;
        3. appraisal nutritionally: global, personal and non-surgical&#xD;
&#xD;
        4. considered only after medical treatment for a minimum of 1 year&#xD;
&#xD;
        5. well-informed and motivated patients, with acceptable surgical risks&#xD;
&#xD;
        6. obesity stable (or worsening) for five years&#xD;
&#xD;
        7. absence of endocrine pathology (adrenal, thyroid) may be due to obesity&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">November 2015</completion_date>
  <primary_completion_date type="Actual">November 2015</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>To validate the use of serum tests, FibroScan / CAP abdominal MRI for the diagnosis of severe steatosis and / or NASH (specificity, sensitivity, positive and negative predictive values)</measure>
    <time_frame>3 months</time_frame>
    <description>serum tests, FibroScan/CAP abdominal MRI</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Histological lesions of liver fibrosis and quantification of abdominal fat by MRI</measure>
    <time_frame>3 months</time_frame>
    <description>quantification of abdominal fat by MRI in the form of three variables of interest: quantification of the surface of the visceral fat from the surface of the subcutaneous fat and the amount of intrahepatic fat assessed by the percentage loss of signal</description>
  </secondary_outcome>
  <enrollment type="Actual">186</enrollment>
  <condition>Morbid Obesity</condition>
  <condition>Non Alcoholic Steatohepatitis</condition>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      blood, liver biopsy&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        morbidly obese patients undergoing bariatric surgery&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  BMI ≥ 35 kg/m2&#xD;
&#xD;
          -  Bariatric surgery scheduled within 3 months following the inclusion&#xD;
&#xD;
          -  Conducting a medical examination.&#xD;
&#xD;
          -  Signature of informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient non-affiliated to a social security scheme (beneficiary or assignee)&#xD;
&#xD;
          -  Cons-indication for performing an MRI&#xD;
&#xD;
          -  weight&gt; 230 kg , anteroposterior diameter&gt;40 cm&#xD;
&#xD;
          -  Cancer treatment or medication that may induce lesions of steatohepatitis (corticoids,&#xD;
             methotrexate, amiodarone, perhexiline, tamoxifen, nifedipine, diltiazem, hycanthone)&#xD;
&#xD;
          -  Alcohol consumption &gt; 20 g per day for women and &gt; 30 g per day for men AND no past&#xD;
             history of excessive alcohol use for more than a 2-year period within the last 20&#xD;
             years&#xD;
&#xD;
          -  known chronic liver disease other than steatosis (presence of HBs antigen, or antibody&#xD;
             to HCV, or anti-nuclear antibodies, anti-mitochondria, anti-LKM1, anti-smooth muscle&#xD;
             negative, or the presence of a hemochromatosis),&#xD;
&#xD;
          -  known HIV positive status&#xD;
&#xD;
          -  Pregnant women (known pregnancy) or lactating&#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_official>
    <last_name>Pauline Jouët, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hôpital Louis Mourier</name>
      <address>
        <city>Colombes</city>
        <zip>92700</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>September 2016</verification_date>
  <study_first_submitted>September 25, 2012</study_first_submitted>
  <study_first_submitted_qc>September 25, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 27, 2012</study_first_posted>
  <last_update_submitted>December 18, 2019</last_update_submitted>
  <last_update_submitted_qc>December 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 19, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Non alcoholic steatohepatitis</keyword>
  <keyword>Liver fibrosis,Steatosis</keyword>
  <keyword>Liver inflammation</keyword>
  <keyword>Morbid obesity</keyword>
  <keyword>Non invasive tests</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fatty Liver</mesh_term>
    <mesh_term>Non-alcoholic Fatty Liver Disease</mesh_term>
    <mesh_term>Obesity, Morbid</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
    <mesh_term>Inflammation</mesh_term>
  </condition_browse>
  <!-- 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/NCT01695083
org study id: P091119
secondary id: 2011-A00829-32
nct id: NCT01695083
lead sponsor: 
has dmc: No
Abstract:

      Fatty liver most frequently corresponds to a fat overload of the liver. It is usually
      classified as alcoholic steatosis or non-alcoholic steatosis. In the case of non alcoholic
      fatty liver overload, the histological spectrum ranges from simple steatosis to
      steatohepatitis (NASH) which associates inflammation to steatosis, with a risk of progression
      to fibrosis and cirrhosis. Obese patients are at particular risk of NASH. Screening of these
      hepatic lesions is difficult especially as they may exist while the liver tests are normal.
      The diagnosis of NASH is currently done by liver biopsy, which exposes them in particular to
      the risk of hemorrhagic complications.

      Number of subjects required:

      According to the literature and data collected Louis Mourier in the recent years, the
      inclusion of 200 patients would examine 20-40 patients with severe histological steatosis and
      steatohepatitis. All patients will be included in Louis Mourier hospital.

      Follow-up: one month Search duration: 37 months Duration inclusions: 36 months The total
      duration of participation for a patient will be one month.

      Methodology:

      It is a monocentric, prospective study evaluating the value of noninvasive tests for the
      diagnosis of hepatic lesions in morbid obese patients. The "open " MRI system allows access
      to MRI for all obese patients (maximum weight 250 kg). Three of such systems are available in
      France and liver pathology can be explored only on the system of Louis Mourier.

      The reference method is liver histology; studied tests are abdominal MRI, Fibroscan / CAP,
      and serum tests.

      Examinations required specifically for research Examinations required specifically for the
      research is abdominal MRI, FibroScan/ CAP and serum tests.

      Primary endpoint :

      To validate the use of abdominal MRI, the FibroScan/ CAP and serum tests for finding severe
      steatosis and / or NASH, specificity, sensitivity, positive and negative predictive values of
      these tests are calculated. The gold standard is the result of histology on liver biopsy,
      with a morphometric study of these parameters. ROC curves are used to determine the best
      compromise between sensitivity and specificity.

      The secondary endpoints were:

      Histological lesions of liver fibrosis. Quantification of abdominal fat by MRI (in the form
      of three variables of interest: quantification of the surface of the visceral fat, of
      subcutaneous fat and of intrahepatic fat assessed by the percentage loss of signal
Main objective :

      The main objective of the study was to determine in patients with morbid obesity waiting for
      bariatric surgery, the accuracy of non-invasive tests for diagnosis of severe steatosis and /
      or NASH.

      The gold standard is liver biopsy with a morphometric study.

      Non-invasive tests will be used:

        -  Serum tests: the FibroMax (which includes the NASH test, FibroTest and SteatoTest) and
           FibroMeter.

        -  Radiological examinations: MRI and FibroScan / CAP

      Secondary objectives :

      The secondary objectives are:

        1. to determine the accuracy of these non-invasive tests for the diagnosis of severe
           steatosis alone, steatohepatitis (NASH or) and hepatic fibrosis

        2. to determine the best combination of these tests to better evaluate the presence of
           severe steatosis, NASH and a hepatic fibrosis.

        3. to quantify MRI visceral and subcutaneous fat in morbidly obese patients

      Research Design :

        1. Judging Criteria

           Primary endpoint To validate the use of serum tests, FibroScan / CAP abdominal MRI for
           the diagnosis of severe steatosis and / or NASH (specificity, sensitivity, positive and
           negative predictive values). The gold standard is the result of histology on liver
           biopsy, with a morphometric study. For each diagnostic test, a ROC curve is used to
           determine the best compromise between sensitivity and specificity.

           The histological diagnosis of severe steatosis is defined by the presence of hepatic
           steatosis grade 3 or higher. The diagnosis of NASH is defined by the presence of lobular
           inflammation with neutrophils and hepatocytes ballooning.

           Secondary endpoints

           - Histological lesions of liver fibrosis Quantification of abdominal fat by MRI (in the
           form of three variables of interest: quantification of the surface of the visceral fat
           from the surface of the subcutaneous fat and the amount of intrahepatic fat assessed by
           the percentage loss of signal).

        2. Methodology and expected number of patients in research

           This is a prospective study evaluating the value of noninvasive tests for the diagnosis
           of hepatic lesions in morbid obese patients. The MRI system "open" allows access to
           obese patients. Three such systems are available in France and liver pathology is
           supported only on the system of Louis Mourier.

           The reference method is liver histology; tests studied are MRI abdominal Fibroscan /
           CAP, and serum tests (FibroTest, FibroMeter, SteatoTest, NASH test).

           The study will be conducted in 200 obese patients who will have a liver biopsy performed
           during bariatric surgery:

             -  Tests for the detection of steatosis (fat quantification of intrahepatic MRI
                measurement of steatosis by CAP, serum tests) and evaluating histological steatosis
                (main objective)

             -  Tests for the detection of NASH (test serum) and histology

             -  Tests of fibrosis (serum tests; FibroScan) and histological data assessing
                fibrosis.

           The duration and extent of obesity (BMI) and biological data (HOMA-test) will be taken
           into account.

        3. Examinations required specifically for research

           Liver biopsy is routinely performed intraoperatively in the routine monitoring of
           patients for bariatric surgery, examinations specific to the research are:

             -  Serum tests

             -  FibroScan / CAP

             -  Abdominal MRI

           Risk / risk absences The sting at blood sampling can cause the formation of a small
           hematoma without gravity, which will subside spontaneously within a few days.

           FibroScan ® / CAP presents no risk of side effects. Liver MRI shows no risk if the
           cons-indications are respected. Wearing a stack (pacemaker) or any element that contains
           the iron near the eyes or head are contra-indications as are a major risk factor (risk
           of death, blindness). The presence of a heart valve or a stent (also called metal
           prosthesis) is not an absolute contra-indication-and their compatibility with MRI will
           be verified before completion of the examination, as is the case in practice clinic ..

           Liver biopsy, which is part of the examinations carried out in a systematic way without
           any protocol adds no additional risk to the surgical

        4. Study site

           The study will be conducted at Louis Mourier, a reference center for the treatment of
           obesity, which has an open system allowing access to obese.

        5. Indications for bariatric surgery

      Indications for bariatric surgery at Louis Mourier, a reference center for the treatment of
      obesity, are consistent with the recommendations of the HAS in 2009, based on professional
      consensus.

      Surgery is indicated in patients with all of the following criteria:

        1. BMI ≥ 40 or BMI ≥ 35 with comorbid

        2. failure (s) prior (s) of the conventional treatment of obesity combined dietary,
           physical activity and behavioral therapy

        3. appraisal nutritionally: global, personal and non-surgical

        4. considered only after medical treatment for a minimum of 1 year

        5. well-informed and motivated patients, with acceptable surgical risks

        6. obesity stable (or worsening) for five years

        7. absence of endocrine pathology (adrenal, thyroid) may be due to obesity
observational model: Case-Only
time perspective: Prospective
measure: To validate the use of serum tests, FibroScan / CAP abdominal MRI for the diagnosis of severe steatosis and / or NASH (specificity, sensitivity, positive and negative predictive values)
time frame: 3 months
description: serum tests, FibroScan/CAP abdominal MRI
measure: Histological lesions of liver fibrosis and quantification of abdominal fat by MRI
time frame: 3 months
description: quantification of abdominal fat by MRI in the form of three variables of interest: quantification of the surface of the visceral fat from the surface of the subcutaneous fat and the amount of intrahepatic fat assessed by the percentage loss of signal
blood, liver biopsy
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Pauline Jouët, MD
role: Principal Investigator
affiliation: Assistance Publique - Hôpitaux de Paris
facility: 
country: France
responsible party type: Sponsor
mesh term: Fatty Liver
mesh term: Non-alcoholic Fatty Liver Disease
mesh term: Obesity, Morbid
mesh term: Fibrosis
mesh term: Inflammation