<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/NCT02206841</url>
  </required_header>
  <id_info>
    <org_study_id>NAFLD_cohort</org_study_id>
    <nct_id>NCT02206841</nct_id>
  </id_info>
  <brief_title>Establishment of NAFLD Cohort and Development of Fibrosis Markers</brief_title>
  <acronym>NAFLD</acronym>
  <official_title>Establishment of Non-alcoholic Fatty Liver Disease Cohort and Development of Markers to Predict Histologic Progression of Liver Fibrosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Seoul National University Boramae Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Seoul National University Boramae Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is designed for establishment of non-alcoholic fatty liver disease patients cohort&#xD;
      to development of markers to predict histologic progression of liver fibrosis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      -  Acoustic radiation force impulse elastography and transient elastography&#xD;
&#xD;
        -  Liver tissue (frozen tissue, paraffin block)&#xD;
&#xD;
        -  Whole blood, Serum&#xD;
&#xD;
        -  Fat amount ratio CT (Visceral adipose tissue, Subcutaneous adipose tissue amount)&#xD;
&#xD;
        -  Body composition analyzer (InBody scale):Total fat/muscle mass and appendicular skeletal&#xD;
           muscle mass&#xD;
&#xD;
        -  Pulmonary function test with post-bronchodilator response and DLCo&#xD;
&#xD;
        -  EKG, EchoCG, Heart CT (Coronary calcium score), and Pusle wave velocity (AI index,&#xD;
           arterial stiffness)&#xD;
&#xD;
        -  Brain MRI or CT&#xD;
&#xD;
        -  Upper esophagogastroscopy and colonoscopy&#xD;
&#xD;
        -  Berlin score questionnaire and Polysomnography&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date>June 2014</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">August 2023</primary_completion_date>
  <study_type>Observational [Patient Registry]</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>
  <target_duration>3 Years</target_duration>
  <primary_outcome>
    <measure>histologic steatosis and fibrosis grade</measure>
    <time_frame>baseline</time_frame>
    <description>We will evaluate fibrosis using laboratory examination, radiologic evaluation and liver tissue pathology.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Development of markers for hepatic fibrosis progression</measure>
    <time_frame>baseline and every 6 months (up to 1year)</time_frame>
    <description>We will analysis and development fibrosis markers by obtained blood sample and liver tissue,</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">1000</enrollment>
  <condition>Fibrosis of Liver</condition>
  <arm_group>
    <arm_group_label>NAFLD</arm_group_label>
    <description>Patients with suspected nonalcoholic fatty liver disease will be screened. Of all patients fulfilling inclusion criteria, baseline characteristics will be obtained. In addition, laboratory, radiologic evaluations such as ARFI, SWE, and transient elastography will be performed. A diagnostic liver biopsy will be performed for analysis of steatosis and fibrosis. Parts of the remaining liver tissue will be stored by frozen tissue and paraffin block for future study. Several serum and plasma samples are collected of patients and stored for future analysis such as targeted SNP arrays, super-enhancer RNA (eRNA) expression, whole exome sequencing, RNA chip sequencing, RNA microarray, genomic DNA, metabolomics, fecal microbiome, metabolite, metagenome/metatranscriptome analyses.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Liver biopsy</intervention_name>
    <description>Percutaneously liver biopsy will be performed for evaluate steatosis and fibrosis.</description>
    <arm_group_label>NAFLD</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>ARFI</intervention_name>
    <description>Acoustic radiation force impulse (ARFI) imaging will be performed for evaluate fibrosis of liver.</description>
    <arm_group_label>NAFLD</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>SWE</intervention_name>
    <description>Supersonic shear wave elastography (SWE) will be performed for evaluate fibrosis of liver.</description>
    <arm_group_label>NAFLD</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Transient elastography</intervention_name>
    <description>Transient elastography will be performed for evaluate fibrosis of liver.</description>
    <arm_group_label>NAFLD</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Obtained blood samples will be stored by serum and plasma for future analysis.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Non-alcoholic fatty liver disease&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with histologically confirmed fatty liver disease&#xD;
&#xD;
          -  Patients with radiologically confirmed fatty liver disease&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of significant alcohol consumption&#xD;
&#xD;
          -  Viral hepatitis&#xD;
&#xD;
          -  Autoimmune hepatitis&#xD;
&#xD;
          -  Metabolic diseases (e.g. hemochromatosis, M. Wilson, alpha 1-antitrypsin deficiency)&#xD;
&#xD;
          -  Hepatotoxic medication (e.g. amiodarone)&#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>Won Kim, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>SMG-SNU Boramae Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Won Kim, MD,PhD</last_name>
    <phone>8228702233</phone>
    <email>drwon1@snu.ac.kr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Saekyung Joo, MD</last_name>
    <phone>821089619285</phone>
    <email>joo.sammy@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Seoul Metropolitan Government Seoul National University</name>
      <address>
        <city>Seoul</city>
        <zip>156-707</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Won Kim, MD, PhD</last_name>
      <phone>8228702233</phone>
      <email>drwon1@snu.ac.kr</email>
    </contact>
    <investigator>
      <last_name>Won Kim, MD,PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <results_reference>
    <citation>Koo BK, Joo SK, Kim D, Bae JM, Park JH, Kim JH, Kim W. Additive effects of PNPLA3 and TM6SF2 on the histological severity of non-alcoholic fatty liver disease. J Gastroenterol Hepatol. 2018 Jun;33(6):1277-1285. doi: 10.1111/jgh.14056. Epub 2018 Feb 26.</citation>
    <PMID>29193269</PMID>
  </results_reference>
  <results_reference>
    <citation>Koo BK, Um SH, Seo DS, Joo SK, Bae JM, Park JH, Chang MS, Kim JH, Lee J, Jeong WI, Kim W. Growth differentiation factor 15 predicts advanced fibrosis in biopsy-proven non-alcoholic fatty liver disease. Liver Int. 2018 Apr;38(4):695-705. doi: 10.1111/liv.13587. Epub 2017 Sep 30.</citation>
    <PMID>28898507</PMID>
  </results_reference>
  <results_reference>
    <citation>Joo SK, Kim W, Kim D, Kim JH, Oh S, Lee KL, Chang MS, Jung YJ, So YH, Lee MS, Bae JM, Kim BG. Steatosis severity affects the diagnostic performances of noninvasive fibrosis tests in nonalcoholic fatty liver disease. Liver Int. 2018 Feb;38(2):331-341. doi: 10.1111/liv.13549. Epub 2017 Sep 5.</citation>
    <PMID>28796410</PMID>
  </results_reference>
  <results_reference>
    <citation>Kim D, Kim W, Joo SK, Bae JM, Kim JH, Ahmed A. Subclinical Hypothyroidism and Low-Normal Thyroid Function Are Associated With Nonalcoholic Steatohepatitis and Fibrosis. Clin Gastroenterol Hepatol. 2018 Jan;16(1):123-131.e1. doi: 10.1016/j.cgh.2017.08.014. Epub 2017 Aug 18.</citation>
    <PMID>28823829</PMID>
  </results_reference>
  <results_reference>
    <citation>Kim JY, Park KJ, Hwang JY, Kim GH, Lee D, Lee YJ, Song EH, Yoo MG, Kim BJ, Suh YH, Roh GS, Gao B, Kim W, Kim WH. Activating transcription factor 3 is a target molecule linking hepatic steatosis to impaired glucose homeostasis. J Hepatol. 2017 Aug;67(2):349-359. doi: 10.1016/j.jhep.2017.03.023. Epub 2017 Mar 30.</citation>
    <PMID>28365312</PMID>
  </results_reference>
  <results_reference>
    <citation>Koo BK, Kim D, Joo SK, Kim JH, Chang MS, Kim BG, Lee KL, Kim W. Sarcopenia is an independent risk factor for non-alcoholic steatohepatitis and significant fibrosis. J Hepatol. 2017 Jan;66(1):123-131. doi: 10.1016/j.jhep.2016.08.019. Epub 2016 Sep 4.</citation>
    <PMID>27599824</PMID>
  </results_reference>
  <results_reference>
    <citation>Lee MS, Bae JM, Joo SK, Woo H, Lee DH, Jung YJ, Kim BG, Lee KL, Kim W. Prospective comparison among transient elastography, supersonic shear imaging, and ARFI imaging for predicting fibrosis in nonalcoholic fatty liver disease. PLoS One. 2017 Nov 27;12(11):e0188321. doi: 10.1371/journal.pone.0188321. eCollection 2017. Erratum In: PLoS One. 2018 Jun 26;13(6):e0200055.</citation>
    <PMID>29176844</PMID>
  </results_reference>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>July 28, 2014</study_first_submitted>
  <study_first_submitted_qc>July 30, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 1, 2014</study_first_posted>
  <last_update_submitted>May 3, 2022</last_update_submitted>
  <last_update_submitted_qc>May 3, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 5, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Seoul National University Boramae Hospital</investigator_affiliation>
    <investigator_full_name>Won Kim</investigator_full_name>
    <investigator_title>M.D, PhD</investigator_title>
  </responsible_party>
  <keyword>fibrosis</keyword>
  <keyword>markers</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fibrosis</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/NCT02206841
org study id: NAFLD_cohort
nct id: NCT02206841
lead sponsor: 
has dmc: No
This study is designed for establishment of non-alcoholic fatty liver disease patients cohort
      to development of markers to predict histologic progression of liver fibrosis.
-  Acoustic radiation force impulse elastography and transient elastography

        -  Liver tissue (frozen tissue, paraffin block)

        -  Whole blood, Serum

        -  Fat amount ratio CT (Visceral adipose tissue, Subcutaneous adipose tissue amount)

        -  Body composition analyzer (InBody scale):Total fat/muscle mass and appendicular skeletal
           muscle mass

        -  Pulmonary function test with post-bronchodilator response and DLCo

        -  EKG, EchoCG, Heart CT (Coronary calcium score), and Pusle wave velocity (AI index,
           arterial stiffness)

        -  Brain MRI or CT

        -  Upper esophagogastroscopy and colonoscopy

        -  Berlin score questionnaire and Polysomnography
observational model: Cohort
time perspective: Prospective
measure: histologic steatosis and fibrosis grade
time frame: baseline
description: We will evaluate fibrosis using laboratory examination, radiologic evaluation and liver tissue pathology.
measure: Development of markers for hepatic fibrosis progression
time frame: baseline and every 6 months (up to 1year)
description: We will analysis and development fibrosis markers by obtained blood sample and liver tissue,
arm group label: NAFLD
description: Patients with suspected nonalcoholic fatty liver disease will be screened. Of all patients fulfilling inclusion criteria, baseline characteristics will be obtained. In addition, laboratory, radiologic evaluations such as ARFI, SWE, and transient elastography will be performed. A diagnostic liver biopsy will be performed for analysis of steatosis and fibrosis. Parts of the remaining liver tissue will be stored by frozen tissue and paraffin block for future study. Several serum and plasma samples are collected of patients and stored for future analysis such as targeted SNP arrays, super-enhancer RNA (eRNA) expression, whole exome sequencing, RNA chip sequencing, RNA microarray, genomic DNA, metabolomics, fecal microbiome, metabolite, metagenome/metatranscriptome analyses.
intervention type: Procedure
intervention name: Liver biopsy
description: Percutaneously liver biopsy will be performed for evaluate steatosis and fibrosis.
arm group label: NAFLD
intervention type: Device
intervention name: ARFI
description: Acoustic radiation force impulse (ARFI) imaging will be performed for evaluate fibrosis of liver.
arm group label: NAFLD
intervention type: Device
intervention name: SWE
description: Supersonic shear wave elastography (SWE) will be performed for evaluate fibrosis of liver.
arm group label: NAFLD
intervention type: Device
intervention name: Transient elastography
description: Transient elastography will be performed for evaluate fibrosis of liver.
arm group label: NAFLD
Obtained blood samples will be stored by serum and plasma for future analysis.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Won Kim, Professor
role: Principal Investigator
affiliation: SMG-SNU Boramae Medical Center
last name: Won Kim, MD,PhD
phone: 8228702233
email: drwon1@snu.ac.kr
last name: Saekyung Joo, MD
phone: 821089619285
email: joo.sammy@gmail.com
facility: 
status: Recruiting
contact: 
investigator: 
country: Korea, Republic of
citation: Koo BK, Joo SK, Kim D, Bae JM, Park JH, Kim JH, Kim W. Additive effects of PNPLA3 and TM6SF2 on the histological severity of non-alcoholic fatty liver disease. J Gastroenterol Hepatol. 2018 Jun;33(6):1277-1285. doi: 10.1111/jgh.14056. Epub 2018 Feb 26.
PMID: 29193269
citation: Koo BK, Um SH, Seo DS, Joo SK, Bae JM, Park JH, Chang MS, Kim JH, Lee J, Jeong WI, Kim W. Growth differentiation factor 15 predicts advanced fibrosis in biopsy-proven non-alcoholic fatty liver disease. Liver Int. 2018 Apr;38(4):695-705. doi: 10.1111/liv.13587. Epub 2017 Sep 30.
PMID: 28898507
citation: Joo SK, Kim W, Kim D, Kim JH, Oh S, Lee KL, Chang MS, Jung YJ, So YH, Lee MS, Bae JM, Kim BG. Steatosis severity affects the diagnostic performances of noninvasive fibrosis tests in nonalcoholic fatty liver disease. Liver Int. 2018 Feb;38(2):331-341. doi: 10.1111/liv.13549. Epub 2017 Sep 5.
PMID: 28796410
citation: Kim D, Kim W, Joo SK, Bae JM, Kim JH, Ahmed A. Subclinical Hypothyroidism and Low-Normal Thyroid Function Are Associated With Nonalcoholic Steatohepatitis and Fibrosis. Clin Gastroenterol Hepatol. 2018 Jan;16(1):123-131.e1. doi: 10.1016/j.cgh.2017.08.014. Epub 2017 Aug 18.
PMID: 28823829
citation: Kim JY, Park KJ, Hwang JY, Kim GH, Lee D, Lee YJ, Song EH, Yoo MG, Kim BJ, Suh YH, Roh GS, Gao B, Kim W, Kim WH. Activating transcription factor 3 is a target molecule linking hepatic steatosis to impaired glucose homeostasis. J Hepatol. 2017 Aug;67(2):349-359. doi: 10.1016/j.jhep.2017.03.023. Epub 2017 Mar 30.
PMID: 28365312
citation: Koo BK, Kim D, Joo SK, Kim JH, Chang MS, Kim BG, Lee KL, Kim W. Sarcopenia is an independent risk factor for non-alcoholic steatohepatitis and significant fibrosis. J Hepatol. 2017 Jan;66(1):123-131. doi: 10.1016/j.jhep.2016.08.019. Epub 2016 Sep 4.
PMID: 27599824
citation: Lee MS, Bae JM, Joo SK, Woo H, Lee DH, Jung YJ, Kim BG, Lee KL, Kim W. Prospective comparison among transient elastography, supersonic shear imaging, and ARFI imaging for predicting fibrosis in nonalcoholic fatty liver disease. PLoS One. 2017 Nov 27;12(11):e0188321. doi: 10.1371/journal.pone.0188321. eCollection 2017. Erratum In: PLoS One. 2018 Jun 26;13(6):e0200055.
PMID: 29176844
responsible party type: Principal Investigator
investigator affiliation: Seoul National University Boramae Hospital
investigator full name: Won Kim
investigator title: M.D, PhD
mesh term: Fibrosis
sharing ipd: No