<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/NCT03027700</url>
  </required_header>
  <id_info>
    <org_study_id>CIN001- Liver Fibrosis</org_study_id>
    <nct_id>NCT03027700</nct_id>
  </id_info>
  <brief_title>Methods to Detect Liver Fibrosis</brief_title>
  <official_title>Comparison of Non-invasive Methods to Detect and Quantify Liver Fibrosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Children's Hospital Medical Center, Cincinnati</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Children's Hospital Medical Center, Cincinnati</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>
      The goal of this study is to learn more about liver fibrosis and methods to detect it. We&#xD;
      will evaluate and compare multiple MRI based measures of liver fibrosis in subjects with and&#xD;
      without liver disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      While liver biopsy is still considered the gold standard for diagnosing and assessing the&#xD;
      presence and degree of liver fibrosis and inflammation, it has disadvantages including the&#xD;
      potential for sampling error and risk of complications, including life-threatening bleeding.&#xD;
      New imaging modalities such as MR Elastography, T1 mapping, T2 mapping, T1 rho, and&#xD;
      magnetization transfer allow rapid, non-invasive evaluation of liver parenchymal&#xD;
      characteristics and may be able to detect and quantify parenchymal fibrosis alleviating the&#xD;
      need for biopsy. To date, the quantitative performance of these different techniques has not&#xD;
      been extensively studied. This study is a single-center trial of non-invasive MR imaging&#xD;
      techniques aimed at detecting and measuring liver fibrosis. Once optimized, these&#xD;
      technologies may later be deployed in hypothesis driven research studies and/or routine&#xD;
      clinical exams in the pediatric population here at CCHMC and/or as part of a multi-center&#xD;
      study with specific IRB approval for that project.&#xD;
&#xD;
      To assess the relative performance of each technique, correlation across techniques, and&#xD;
      reproducibility across the range of fibrosis, 32 subjects will be enrolled in this&#xD;
      preliminary study sub-divided into 4 groups (Group 1: Healthy/ Normal controls; Group 2:&#xD;
      F1/F2 fibrosis as determined by prior biopsy (low grade fibrosis group); Group 3: F3/F4&#xD;
      fibrosis as determined by prior biopsy (high grade fibrosis group), Group 4: Hepatic&#xD;
      steatosis with fibrosis (NAFLD group)). 8 healthy subjects without known or suspected liver&#xD;
      disease will be enrolled as normal controls. 8 subjects each with known fibrosis based on&#xD;
      liver biopsy within the last 6 months will be enrolled in Group 2 and Group 3 (total = 16). 8&#xD;
      subjects with known hepatic steatosis and liver fibrosis based on liver biopsy within the&#xD;
      last 6 months will be enrolled in Group 4.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Inadequate recruitment&#xD;
  </why_stopped>
  <start_date type="Actual">January 26, 2017</start_date>
  <completion_date type="Actual">December 30, 2018</completion_date>
  <primary_completion_date type="Actual">December 30, 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>Double (Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>MR imaging vs. histologic scoring in hepatic fibrosis</measure>
    <time_frame>2 years</time_frame>
    <description>Correlate the results from the different imaging sequences designed to detect and quantify hepatic fibrosis</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>MRI reproducibility</measure>
    <time_frame>2 years</time_frame>
    <description>evaluate the reproducibility of each of the tested MRI-based liver fibrosis quantification sequences</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Liver Fibroses</condition>
  <condition>Hepatic Steatosis</condition>
  <arm_group>
    <arm_group_label>Health/Normal Controls</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Health/normal control subjects will undergo MRI using several different imaging sequences (MR Elastography, T1 mapping, T2 mapping, T1 rho, and magnetization transfer) designed to detect and quantify hepatic fibrosis.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>F1/F2 fibrosis</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Type 1 and 2 liver fibrosis subjects will undergo MRI using several different imaging sequences (MR Elastography, T1 mapping, T2 mapping, T1 rho, and magnetization transfer) designed to detect and quantify hepatic fibrosis.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>F3/F4 fibrosis</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Type 2 and 3 liver fibrosis subjects will undergo MRI using several different imaging sequences (MR Elastography, T1 mapping, T2 mapping, T1 rho, and magnetization transfer) designed to detect and quantify hepatic fibrosis.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Hepatic steatosis with fibrosis</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Hepatic steatosis with liver fibrosis subjects will undergo MRI using several different imaging sequences (MR Elastography, T1 mapping, T2 mapping, T1 rho, and magnetization transfer) designed to detect and quantify hepatic fibrosis.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>MRI</intervention_name>
    <description>MRI scan performed on 1.5T Philips Ingenia MRI scanner.</description>
    <arm_group_label>F1/F2 fibrosis</arm_group_label>
    <arm_group_label>F3/F4 fibrosis</arm_group_label>
    <arm_group_label>Health/Normal Controls</arm_group_label>
    <arm_group_label>Hepatic steatosis with fibrosis</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
        Group 1:&#xD;
&#xD;
          1. Healthy subjects with no known or suspected liver disease&#xD;
&#xD;
          2. Age 8 - 21 years&#xD;
&#xD;
        Groups 2 and 3:&#xD;
&#xD;
          1. Biopsy confirmed liver fibrosis (F1/F2 Group 2, F3/F4 Group 3)&#xD;
&#xD;
          2. Age 8 - 21 years&#xD;
&#xD;
        Group 4:&#xD;
&#xD;
          1. Biopsy confirmed hepatic steatosis AND biopsy confirmed liver fibrosis (any stage)&#xD;
&#xD;
          2. Age 8 - 21 years&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
        All subjects:&#xD;
&#xD;
          1. Subjects &lt;8 years of age and &gt;21 years of age.&#xD;
&#xD;
          2. BMI &gt; 35 kg/m2&#xD;
&#xD;
          3. Subjects deemed to possibly require sedation to undergo MR imaging&#xD;
&#xD;
          4. Inability to lie still for 90 minutes&#xD;
&#xD;
          5. Routine exclusions to MRI - e.g., implanted hardware&#xD;
&#xD;
          6. Pregnancy (verbal pregnancy screens - per standard practice in Radiology - will be&#xD;
             administered to all female participants of child-bearing age at the time of enrollment&#xD;
             and again immediately prior to imaging)&#xD;
&#xD;
          7. Prior history of liver transplantation&#xD;
&#xD;
        Group 1&#xD;
&#xD;
          1. ALT ≥30 U/L&#xD;
&#xD;
          2. Clinical history or lab/biopsy results suggestive of the presence of liver disease&#xD;
             including: steatosis, fibrosis, inflammation, tumor, etc.&#xD;
&#xD;
        Group 2 and 3&#xD;
&#xD;
          1. Diagnosis of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis&#xD;
&#xD;
          2. Biopsy &gt;6 months prior to research MRI examination&#xD;
&#xD;
          3. Initiation of any medications (e.g. steroids, immunosuppressants, antivirals) or&#xD;
             procedures (e.g. Kasai portoenterostomy) to treat the liver disease during the time&#xD;
             between liver biopsy and study visit&#xD;
&#xD;
        Group 4&#xD;
&#xD;
          1. Biopsy &gt;6 months prior to research MRI examination&#xD;
&#xD;
          2. Hepatic fat fraction &gt;5%&#xD;
&#xD;
          3. Substantial weight loss (&gt;10% of weight at time of biopsy) during the time between&#xD;
             biopsy and study visit&#xD;
&#xD;
          4. Initiation of any medications to treat NAFLD (e.g. vitamin E) during the time between&#xD;
             biopsy and study visit&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>8 Years</minimum_age>
    <maximum_age>21 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Cincinnati Children's Hospital Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Sporea I, Bota S, Jurchis A, Sirli R, Gradinaru-Tascau O, Popescu A, Ratiu I, Szilaski M. Acoustic radiation force impulse and supersonic shear imaging versus transient elastography for liver fibrosis assessment. Ultrasound Med Biol. 2013 Nov;39(11):1933-41. doi: 10.1016/j.ultrasmedbio.2013.05.003. Epub 2013 Aug 9.</citation>
    <PMID>23932281</PMID>
  </reference>
  <reference>
    <citation>Xanthakos SA, Podberesky DJ, Serai SD, Miles L, King EC, Balistreri WF, Kohli R. Use of magnetic resonance elastography to assess hepatic fibrosis in children with chronic liver disease. J Pediatr. 2014 Jan;164(1):186-8. doi: 10.1016/j.jpeds.2013.07.050. Epub 2013 Sep 21.</citation>
    <PMID>24064151</PMID>
  </reference>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>January 19, 2017</study_first_submitted>
  <study_first_submitted_qc>January 19, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 23, 2017</study_first_posted>
  <last_update_submitted>January 27, 2020</last_update_submitted>
  <last_update_submitted_qc>January 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 29, 2020</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>Liver Cirrhosis</mesh_term>
    <mesh_term>Fatty Liver</mesh_term>
    <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/NCT03027700
org study id: CIN001- Liver Fibrosis
nct id: NCT03027700
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The goal of this study is to learn more about liver fibrosis and methods to detect it. We
      will evaluate and compare multiple MRI based measures of liver fibrosis in subjects with and
      without liver disease.
While liver biopsy is still considered the gold standard for diagnosing and assessing the
      presence and degree of liver fibrosis and inflammation, it has disadvantages including the
      potential for sampling error and risk of complications, including life-threatening bleeding.
      New imaging modalities such as MR Elastography, T1 mapping, T2 mapping, T1 rho, and
      magnetization transfer allow rapid, non-invasive evaluation of liver parenchymal
      characteristics and may be able to detect and quantify parenchymal fibrosis alleviating the
      need for biopsy. To date, the quantitative performance of these different techniques has not
      been extensively studied. This study is a single-center trial of non-invasive MR imaging
      techniques aimed at detecting and measuring liver fibrosis. Once optimized, these
      technologies may later be deployed in hypothesis driven research studies and/or routine
      clinical exams in the pediatric population here at CCHMC and/or as part of a multi-center
      study with specific IRB approval for that project.

      To assess the relative performance of each technique, correlation across techniques, and
      reproducibility across the range of fibrosis, 32 subjects will be enrolled in this
      preliminary study sub-divided into 4 groups (Group 1: Healthy/ Normal controls; Group 2:
      F1/F2 fibrosis as determined by prior biopsy (low grade fibrosis group); Group 3: F3/F4
      fibrosis as determined by prior biopsy (high grade fibrosis group), Group 4: Hepatic
      steatosis with fibrosis (NAFLD group)). 8 healthy subjects without known or suspected liver
      disease will be enrolled as normal controls. 8 subjects each with known fibrosis based on
      liver biopsy within the last 6 months will be enrolled in Group 2 and Group 3 (total = 16). 8
      subjects with known hepatic steatosis and liver fibrosis based on liver biopsy within the
      last 6 months will be enrolled in Group 4.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: Double (Investigator, Outcomes Assessor)
measure: MR imaging vs. histologic scoring in hepatic fibrosis
time frame: 2 years
description: Correlate the results from the different imaging sequences designed to detect and quantify hepatic fibrosis
measure: MRI reproducibility
time frame: 2 years
description: evaluate the reproducibility of each of the tested MRI-based liver fibrosis quantification sequences
arm group label: Health/Normal Controls
arm group type: Active Comparator
description: Health/normal control subjects will undergo MRI using several different imaging sequences (MR Elastography, T1 mapping, T2 mapping, T1 rho, and magnetization transfer) designed to detect and quantify hepatic fibrosis.
arm group label: F1/F2 fibrosis
arm group type: Active Comparator
description: Type 1 and 2 liver fibrosis subjects will undergo MRI using several different imaging sequences (MR Elastography, T1 mapping, T2 mapping, T1 rho, and magnetization transfer) designed to detect and quantify hepatic fibrosis.
arm group label: F3/F4 fibrosis
arm group type: Active Comparator
description: Type 2 and 3 liver fibrosis subjects will undergo MRI using several different imaging sequences (MR Elastography, T1 mapping, T2 mapping, T1 rho, and magnetization transfer) designed to detect and quantify hepatic fibrosis.
arm group label: Hepatic steatosis with fibrosis
arm group type: Active Comparator
description: Hepatic steatosis with liver fibrosis subjects will undergo MRI using several different imaging sequences (MR Elastography, T1 mapping, T2 mapping, T1 rho, and magnetization transfer) designed to detect and quantify hepatic fibrosis.
intervention type: Device
intervention name: MRI
description: MRI scan performed on 1.5T Philips Ingenia MRI scanner.
arm group label: F1/F2 fibrosis
arm group label: F3/F4 fibrosis
arm group label: Health/Normal Controls
arm group label: Hepatic steatosis with fibrosis
criteria: 
gender: All
minimum age: 8 Years
maximum age: 21 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
citation: Sporea I, Bota S, Jurchis A, Sirli R, Gradinaru-Tascau O, Popescu A, Ratiu I, Szilaski M. Acoustic radiation force impulse and supersonic shear imaging versus transient elastography for liver fibrosis assessment. Ultrasound Med Biol. 2013 Nov;39(11):1933-41. doi: 10.1016/j.ultrasmedbio.2013.05.003. Epub 2013 Aug 9.
PMID: 23932281
citation: Xanthakos SA, Podberesky DJ, Serai SD, Miles L, King EC, Balistreri WF, Kohli R. Use of magnetic resonance elastography to assess hepatic fibrosis in children with chronic liver disease. J Pediatr. 2014 Jan;164(1):186-8. doi: 10.1016/j.jpeds.2013.07.050. Epub 2013 Sep 21.
PMID: 24064151
responsible party type: Sponsor
mesh term: Liver Cirrhosis
mesh term: Fatty Liver
mesh term: Fibrosis
sharing ipd: No