<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/NCT03282305</url>
  </required_header>
  <id_info>
    <org_study_id>NASH_GC-FLC01</org_study_id>
    <nct_id>NCT03282305</nct_id>
  </id_info>
  <brief_title>Great China Fatter Liver Consortium (GC_FLC) Study to Assess the Progress of NAFLD/NASH in Chinese</brief_title>
  <official_title>Prospective Cohort Assessing the Prevalence and Progress of Non-alcoholic Fatty Liver Disease (NAFLD)/Non-alcoholic Steatohepatitis (NASH) in Chinese</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Great China Fatty Liver Consortium Limited</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Chinese University of Hong Kong</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Virginia Commonwealth University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Great China Fatty Liver Consortium Limited</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>
      Nonalcoholic fatty liver disease (NAFLD) is a progressive liver disease ranging from simple&#xD;
      steatosis to cirrhosis of the liver. Nonalcoholic fatty liver (NAFL) without substantial&#xD;
      hepatocellular injury is thought to be relatively benign whereas nonalcoholic steatohepatitis&#xD;
      (NASH) is characterized by hepatocyte steatosis, ballooning, inflammation and varying degrees&#xD;
      of fibrosis from none to cirrhosis. NASH is strongly associated with insulin resistance and&#xD;
      metabolic syndrome and thus is recognized as a major public health concern as the most&#xD;
      prevalent liver disease.&#xD;
&#xD;
      Liver biopsy is the gold standard for a diagnosis of NASH. However, given the large&#xD;
      population of patients at risk for NASH, liver biopsy is not a practical method for&#xD;
      determining which patients may benefit from NASH therapy. Non-invasive methods to estimate&#xD;
      inflammation and fibrosis are in clinical use, but there remains a dichotomy between gold&#xD;
      standard inclusion criteria and end points that are utilized in clinical trials and real&#xD;
      world diagnostic methods that are more common in clinical practice.&#xD;
&#xD;
      Thus, the investigators would like to conduct an observational study to head-to-head compare&#xD;
      the non-invasive methods and liver biopsy in differential liver steatosis and liver biopsy in&#xD;
      a real-world setting. Also, by following up patients for a relatively long time (proposed 10&#xD;
      years), the investigators can present the natural history of disease progression.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      GC-FLC is a cooperative consortium of principal investigators from academic institutions and&#xD;
      community-based sites treating patients with NAFLD and NASH. The investigators will leverage&#xD;
      the multidisciplinary expertise within this network in bio-banking, high-throughput&#xD;
      technologies, and biomedical informatics to give investigators the power to analyze&#xD;
      effectiveness data at many different levels of resolution, ranging from subsets of patients&#xD;
      to very large populations.&#xD;
&#xD;
      GC-FLC will use standardized data collection practices, study data monitoring, and an&#xD;
      comprehensive observational protocol in order to increase the efficiency and minimize costs&#xD;
      associated with performing clinical research while ensuring collection of detailed critical&#xD;
      safety and effectiveness data on prescribed NASH therapies. GC-FLC engages community and&#xD;
      academic practice providers as partners in the research to ensure rapid translation of&#xD;
      research findings into improvement in healthcare quality and outcomes and to help engage&#xD;
      scientists at the interfaces between clinical research and the community. Furthermore, GC-FLC&#xD;
      provides the opportunity to pair-comparison between liver biopsy and non-invasive biomarkers&#xD;
      in differential low-risk and high-risk population for treatment in real world settings.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">April 2018</start_date>
  <completion_date type="Anticipated">December 2029</completion_date>
  <primary_completion_date type="Anticipated">December 2028</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>Histological endpoint</measure>
    <time_frame>10 years</time_frame>
    <description>The change in NASH Clinical Research Network (CRN) score based on liver biopsy</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of all-cause death</measure>
    <time_frame>10 years</time_frame>
    <description>Number of all-cause death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of liver-related death</measure>
    <time_frame>10 years</time_frame>
    <description>Number of liver-related death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of liver transplant</measure>
    <time_frame>10 years</time_frame>
    <description>Number of liver transplant</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of hepatocellular carcinoma (HCC)</measure>
    <time_frame>10 years</time_frame>
    <description>Number of hepatocellular carcinoma (HCC)</description>
  </secondary_outcome>
  <enrollment type="Anticipated">5000</enrollment>
  <condition>Nonalcoholic Fatty Liver</condition>
  <condition>Nonalcoholic Steatohepatitis</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Whole blood will be stored for biomarkers analysis&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Chinese subjects with NAFLD / NASH&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults and children subjects aged &gt;= 6 years old&#xD;
&#xD;
          -  Ability to understand and sign a written informed consent form (ICF) or provide assent&#xD;
             in pediatric subjects&#xD;
&#xD;
          -  Diagnosis of NAFLD; or a definite or probable diagnosis of NASH:&#xD;
&#xD;
               1. A diagnosis of NAFLD will be defined by evidence of hepatic steatosis, either by&#xD;
                  imaging or by histology, with no causes for secondary hepatic fat accumulation&#xD;
                  such as significant alcohol consumption, use of steato-genic medication (e.g.&#xD;
                  valproate, amiodarone, anti-retroviral medications, tetracycline, chronic&#xD;
                  high-dose corticosteroids), or hereditary disorders (e.g. Wilson's disease,&#xD;
                  Wolman disease, cholesteryl-ester storage disease);&#xD;
&#xD;
               2. A definite diagnosis of NASH will be defined by steatohepatitis confirmed by&#xD;
                  biopsy with correlating clinical evidence of non-alcoholic liver disease;&#xD;
&#xD;
               3. A probable diagnosis of NASH will be defined by:&#xD;
&#xD;
                  a.Elevated alanine amino transferase levels (ALT) of &gt;40 U/L; and b.Evidence of&#xD;
                  hepatic steatosis on imaging; or c.Obesity, type 2 diabetes, or pre-diabetes.&#xD;
                  Pre-diabetes is defined by: i.Impaired fasting glucose: 100 mg/dL-125 mg/dL (5.6&#xD;
                  mmol/L-6.9 mmol/L) or; ii.Impaired glucose tolerance: 2-hr plasma glucose (PG) in&#xD;
                  75-g Oral Glucose Tolerance Test (OGTT) 140 mg/dL-199 mg/dL (7.8 mmol/L-11.0&#xD;
                  mmol/L) or; iii.HbA1C: 5.7%-6.4%.&#xD;
&#xD;
                  Exclusion Criteria:&#xD;
&#xD;
          -  Unable to provide written informed consent (or assent in pediatric subjects)&#xD;
&#xD;
          -  Alcohol consumption greater than 21 units/week for males or 14 units/week for females&#xD;
             (one unit of alcohol is half pint of beer [285 mL; 9.64 oz], 1 glass of spirits [25&#xD;
             mL; 0.85 oz] or 1 glass of wine [125 mL; 4.23 oz]&#xD;
&#xD;
          -  Enrolled in NASH-related clinical trials&#xD;
&#xD;
          -  Presence of other forms of chronic liver disease:&#xD;
&#xD;
               1. Chronic hepatitis B (HBsAg positive)&#xD;
&#xD;
               2. Chronic hepatitis C (HCV RNA positive)&#xD;
&#xD;
               3. Iron overload disorders (3-4+ iron on liver biopsy or known hemochromatosis gene&#xD;
                  (HFE) C282Y homozygous with ferritin &gt; 200 ng/ml; note: an elevated ferritin&#xD;
                  alone is common in NASH and is not exclusionary)&#xD;
&#xD;
               4. Autoimmune liver disease (biopsy evidence or clinical diagnosis of autoimmune&#xD;
                  hepatitis or Primary biliary cholangitis (PBC) requiring ongoing treatment,&#xD;
                  imaging evidence of Primary sclerosing cholangitis (PSC))&#xD;
&#xD;
               5. Wilson's disease&#xD;
&#xD;
               6. Alpha-1 antitrypsin mutations that in the opinion of the principal investigator&#xD;
                  is contributing to the patient's liver disease;&#xD;
&#xD;
          -  Prior bariatric surgery unless the surgery was performed more than one year before the&#xD;
             biopsy diagnosis of NASH (i.e., NASH is present despite prior bariatric surgery);&#xD;
&#xD;
          -  Planned bariatric surgery (e.g. gastroplasty, roux-en-Y gastric bypass).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Vincent Wong, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Medicine &amp; Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>George Lau, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Division of Gastroenterology &amp; Hepatology, Humanity &amp; Health Medical Centre, Hong Kong SAR, China.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Arun Sanyal, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Physiology and Molecular Pathology, School of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jing Chen, Ph.D.</last_name>
    <phone>85228184300</phone>
    <email>chenjing@hnhmgl.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Danny Wang, PhD.</last_name>
    <phone>85228184300</phone>
    <email>danny.wang@hnhmgl.com</email>
  </overall_contact_backup>
  <verification_date>February 2018</verification_date>
  <study_first_submitted>September 12, 2017</study_first_submitted>
  <study_first_submitted_qc>September 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 13, 2017</study_first_posted>
  <last_update_submitted>February 4, 2018</last_update_submitted>
  <last_update_submitted_qc>February 4, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 6, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>
  </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/NCT03282305
org study id: NASH_GC-FLC01
nct id: NCT03282305
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Nonalcoholic fatty liver disease (NAFLD) is a progressive liver disease ranging from simple
      steatosis to cirrhosis of the liver. Nonalcoholic fatty liver (NAFL) without substantial
      hepatocellular injury is thought to be relatively benign whereas nonalcoholic steatohepatitis
      (NASH) is characterized by hepatocyte steatosis, ballooning, inflammation and varying degrees
      of fibrosis from none to cirrhosis. NASH is strongly associated with insulin resistance and
      metabolic syndrome and thus is recognized as a major public health concern as the most
      prevalent liver disease.

      Liver biopsy is the gold standard for a diagnosis of NASH. However, given the large
      population of patients at risk for NASH, liver biopsy is not a practical method for
      determining which patients may benefit from NASH therapy. Non-invasive methods to estimate
      inflammation and fibrosis are in clinical use, but there remains a dichotomy between gold
      standard inclusion criteria and end points that are utilized in clinical trials and real
      world diagnostic methods that are more common in clinical practice.

      Thus, the investigators would like to conduct an observational study to head-to-head compare
      the non-invasive methods and liver biopsy in differential liver steatosis and liver biopsy in
      a real-world setting. Also, by following up patients for a relatively long time (proposed 10
      years), the investigators can present the natural history of disease progression.
GC-FLC is a cooperative consortium of principal investigators from academic institutions and
      community-based sites treating patients with NAFLD and NASH. The investigators will leverage
      the multidisciplinary expertise within this network in bio-banking, high-throughput
      technologies, and biomedical informatics to give investigators the power to analyze
      effectiveness data at many different levels of resolution, ranging from subsets of patients
      to very large populations.

      GC-FLC will use standardized data collection practices, study data monitoring, and an
      comprehensive observational protocol in order to increase the efficiency and minimize costs
      associated with performing clinical research while ensuring collection of detailed critical
      safety and effectiveness data on prescribed NASH therapies. GC-FLC engages community and
      academic practice providers as partners in the research to ensure rapid translation of
      research findings into improvement in healthcare quality and outcomes and to help engage
      scientists at the interfaces between clinical research and the community. Furthermore, GC-FLC
      provides the opportunity to pair-comparison between liver biopsy and non-invasive biomarkers
      in differential low-risk and high-risk population for treatment in real world settings.
observational model: Cohort
time perspective: Prospective
measure: Histological endpoint
time frame: 10 years
description: The change in NASH Clinical Research Network (CRN) score based on liver biopsy
measure: Number of all-cause death
time frame: 10 years
description: Number of all-cause death
measure: Number of liver-related death
time frame: 10 years
description: Number of liver-related death
measure: Number of liver transplant
time frame: 10 years
description: Number of liver transplant
measure: Number of hepatocellular carcinoma (HCC)
time frame: 10 years
description: Number of hepatocellular carcinoma (HCC)
Whole blood will be stored for biomarkers analysis
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 6 Years
maximum age: N/A
healthy volunteers: No
last name: Vincent Wong, MD, PhD
role: Principal Investigator
affiliation: Department of Medicine & Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
last name: George Lau, MD, PhD
role: Study Chair
affiliation: Division of Gastroenterology & Hepatology, Humanity & Health Medical Centre, Hong Kong SAR, China.
last name: Arun Sanyal, MD, PhD
role: Study Director
affiliation: Physiology and Molecular Pathology, School of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA
last name: Jing Chen, Ph.D.
phone: 85228184300
email: chenjing@hnhmgl.com
last name: Danny Wang, PhD.
phone: 85228184300
email: danny.wang@hnhmgl.com
responsible party type: Sponsor
mesh term: Fatty Liver
mesh term: Non-alcoholic Fatty Liver Disease