<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/NCT03289897</url>
  </required_header>
  <id_info>
    <org_study_id>PJM124</org_study_id>
    <nct_id>NCT03289897</nct_id>
  </id_info>
  <brief_title>Non-invasive Rapid Assessment of NAFLD Using Magnetic Resonance Imaging With LiverMultiScan</brief_title>
  <acronym>RADIcAL1</acronym>
  <official_title>Non-invasive Rapid Assessment of Non-alcoholic Fatty Liver Disease (NAFLD) Using Magnetic Resonance Imaging With LiverMultiScan (RADIcAL1)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Perspectum</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Coimbra</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital Ulm</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Leiden University Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Liverpool University Hospitals NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital Southampton NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>King's College Hospital NHS Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>NHS Greater Glasgow and Clyde</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Glasgow Royal Infirmary</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ninewells Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Royal Infirmary of Edinburgh</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>St George's University Hospitals NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Perspectum</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>
      A multi-centre randomised controlled trial to determine the implementation and health care&#xD;
      cost of LiverMultiScan vs. routine methodical assessment (standard care) of Non-alcoholic&#xD;
      fatty liver disease (NAFLD) across several European countries.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Non-alcoholic fatty liver disease (NAFLD) is a condition associated with obesity, insulin&#xD;
      resistance and heart disease. Research has shown that fatty liver (steatosis) can lead to a&#xD;
      spectrum of diseases including low grade inflammation (steatohepatitis or non-alcoholic&#xD;
      steatohepatitis (NASH)), cirrhosis or liver failure.&#xD;
&#xD;
      The current method used to diagnose liver dysfunction and failure is with percutaneous liver&#xD;
      biopsy. This is painful and is not without risk, as the liver is a highly vascular organ.&#xD;
      Even with ultrasound guidance, it carries a 1:1000 risk of serious adverse events (e.g.&#xD;
      bleeding, infection, bowel perforation). As a result of these factors, liver biopsy is not&#xD;
      used in all patients with suspected NAFLD/ NASH unless moderate to severe liver disease is&#xD;
      presented or other liver disease need to be excluded. Various diagnostic pathways have&#xD;
      arisen, but in the absence of a clearly non-invasive discriminatory test that can stratify&#xD;
      normal liver, simple steatosis, steatohepatitis and cirrhosis, there is no standardised&#xD;
      pathway.&#xD;
&#xD;
      LiverMultiScan has been tested against liver biopsy and has been shown to be the first&#xD;
      imaging test that can identify early liver disease and predict clinical outcomes accurately.&#xD;
      LiverMultiScan has recently been CE-Marked and FDA-cleared, so is available for clinical use,&#xD;
      but as a new test, it is not yet widely established in clinical practice. This study will&#xD;
      utilise LiverMultiScan and see if it can be the basis of a viable diagnostic pathway in EU&#xD;
      healthcare systems by adopting it in different EU countries, and determining the economic&#xD;
      costs and benefits.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 5, 2017</start_date>
  <completion_date type="Actual">December 31, 2020</completion_date>
  <primary_completion_date type="Actual">December 31, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To investigate whether the introduction of LiverMultiScan as a standardised diagnostic test for liver disease can prove a cost-effective method in different EU territories.</measure>
    <time_frame>1 year</time_frame>
    <description>Proportion of patients with suspected NAFLD incurring liver related hospital consultations and/or liver biopsies, from the date of randomisation to the end of the study follow-up.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Patient satisfaction: questionnaire</measure>
    <time_frame>1 year</time_frame>
    <description>Patient feedback from patient satisfaction questionnaire, at baseline, and all follow-up visits to the end of the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Certainty of diagnosis</measure>
    <time_frame>1 year</time_frame>
    <description>Certainty of diagnosis is defined as binary (yes/no vs. unlikely/probable) at baseline and all follow-up visits to the end of the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of diagnosis</measure>
    <time_frame>1 year</time_frame>
    <description>Frequency of diagnosis is defined as binary (yes/probable vs. no/unlikely) at baseline and all follow-up visits to the end of the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to diagnosis</measure>
    <time_frame>1 year</time_frame>
    <description>Time from randomisation to diagnosis by the physician, as recorded at final follow-up visit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measure resource use</measure>
    <time_frame>1 year</time_frame>
    <description>Rates of liver related outpatient investigations/consultations/hospital admissions per 400 patients during the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cost effectiveness of LiverMultiScan</measure>
    <time_frame>1 year</time_frame>
    <description>Cost of LiverMultiScan based on randomised comparison.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Personnel skills required for diagnosis</measure>
    <time_frame>1 year</time_frame>
    <description>Percentage of total consultations performed by a specialist, at each specialist medical category, from date of randomisation to end of study.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">801</enrollment>
  <condition>NASH - Nonalcoholic Steatohepatitis</condition>
  <condition>NAFLD</condition>
  <condition>Metabolic Syndrome</condition>
  <arm_group>
    <arm_group_label>Study Arm-LiverMultiScan</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be scanned using the LiverMultiScan. Follow-up will be determined by the results of the scan.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Arm</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Standard of care as per guidelines of the local centre</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>LiverMultiScan</intervention_name>
    <description>LiverMultiScan is an imaging technique which is able to identify early liver disease.</description>
    <arm_group_label>Study Arm-LiverMultiScan</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female patients aged 18-75 years, due to undergo evaluation for suspected&#xD;
             non-alcoholic fatty liver disease&#xD;
&#xD;
          -  Presence of:&#xD;
&#xD;
               -  elevated liver function tests (ALT, AST or GGT ≥ 1.5 x upper limit of normal and&#xD;
                  ≤ 5 x upper limit of normal)&#xD;
&#xD;
        OR&#xD;
&#xD;
          -  imaging suggestive of Fatty liver disease.&#xD;
&#xD;
        OR&#xD;
&#xD;
        Presence of ≥ 3 of the following criteria:&#xD;
&#xD;
          1. insulin resistance or type 2 diabetes mellitus&#xD;
&#xD;
          2. obesity (BMI &gt; 30 or waist-to-hip ratio &gt; 1.00 for men / &gt; 0.85 for women)&#xD;
&#xD;
          3. hypertension (≥ 130/85 mmHg)&#xD;
&#xD;
          4. elevated triglycerides (≥ 1.7 mmol/l)&#xD;
&#xD;
          5. low HDL-cholesterol (&lt; 1.05 mmol/l for men / &lt; 1.25 mmol/l for women)&#xD;
&#xD;
               -  Participant is willing and able to give informed consent for participation in the&#xD;
                  study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  The participant may not enter the study if they have any contraindication to magnetic&#xD;
             resonance imaging (inc pregnancy, extensive tattoos, pacemaker, shrapnel injury,&#xD;
             severe claustrophobia).&#xD;
&#xD;
          -  Patients with proven liver disease other than NAFLD.&#xD;
&#xD;
          -  Liver transplantation&#xD;
&#xD;
          -  Patients that present with clinical signs of chronic liver failure (variceal bleeding,&#xD;
             ascites, overt encephalopathy)&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Alcohol over-use/ abuse as determined by local guidelines&#xD;
&#xD;
          -  Patient with known malignant liver tumours and those with any malignancy with life&#xD;
             expectancy &lt; 36 months&#xD;
&#xD;
          -  Heart failure NYHA stages II-IV&#xD;
&#xD;
          -  Severe mental illness&#xD;
&#xD;
          -  Any other cause, including a significant disease or disorder which, in the opinion of&#xD;
             the investigator, may either put the participant at risk because of participation in&#xD;
             the study, or may influence the result of the study, or the participant's ability to&#xD;
             participate in the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Matthias Dollinger, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Ulm</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Dimitar Tonev, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Perspectum Diagnostics</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Ulm</name>
      <address>
        <city>Ulm</city>
        <state>Baden-Württemberg</state>
        <zip>89081</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Leiden University Medical Center</name>
      <address>
        <city>Leiden</city>
        <state>South Holland</state>
        <zip>2333</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Coimbra</name>
      <address>
        <city>Coimbra</city>
        <state>Centro</state>
        <zip>3004-531</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southampton University Hospital</name>
      <address>
        <city>Southampton</city>
        <state>Hampshire</state>
        <zip>SO16 6YD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aintree Hospital</name>
      <address>
        <city>Liverpool</city>
        <state>Merseyside</state>
        <zip>L9 7AL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ninewells Hospital</name>
      <address>
        <city>Dundee</city>
        <zip>DD2 1SG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Infirmary of Edinburgh</name>
      <address>
        <city>Edinburgh</city>
        <zip>EH16 4SA</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Glasgow Royal Infirmary</name>
      <address>
        <city>Glasgow</city>
        <zip>G40SF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen Elizabeth University Hospital</name>
      <address>
        <city>Glasgow</city>
        <zip>G51 4TF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>King's College Hospital</name>
      <address>
        <city>London</city>
        <zip>SE5 9RS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St George's Hospital</name>
      <address>
        <city>London</city>
        <zip>SW170Q2</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>Netherlands</country>
    <country>Portugal</country>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Banerjee R, Pavlides M, Tunnicliffe EM, Piechnik SK, Sarania N, Philips R, Collier JD, Booth JC, Schneider JE, Wang LM, Delaney DW, Fleming KA, Robson MD, Barnes E, Neubauer S. Multiparametric magnetic resonance for the non-invasive diagnosis of liver disease. J Hepatol. 2014 Jan;60(1):69-77. doi: 10.1016/j.jhep.2013.09.002. Epub 2013 Sep 12.</citation>
    <PMID>24036007</PMID>
  </reference>
  <reference>
    <citation>Pavlides M, Banerjee R, Sellwood J, Kelly CJ, Robson MD, Booth JC, Collier J, Neubauer S, Barnes E. Multiparametric magnetic resonance imaging predicts clinical outcomes in patients with chronic liver disease. J Hepatol. 2016 Feb;64(2):308-315. doi: 10.1016/j.jhep.2015.10.009. Epub 2015 Nov 10.</citation>
    <PMID>26471505</PMID>
  </reference>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>September 5, 2017</study_first_submitted>
  <study_first_submitted_qc>September 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 21, 2017</study_first_posted>
  <last_update_submitted>August 21, 2023</last_update_submitted>
  <last_update_submitted_qc>August 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 22, 2023</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>
    <mesh_term>Metabolic Syndrome</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/NCT03289897
org study id: PJM124
nct id: NCT03289897
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
A multi-centre randomised controlled trial to determine the implementation and health care
      cost of LiverMultiScan vs. routine methodical assessment (standard care) of Non-alcoholic
      fatty liver disease (NAFLD) across several European countries.
Non-alcoholic fatty liver disease (NAFLD) is a condition associated with obesity, insulin
      resistance and heart disease. Research has shown that fatty liver (steatosis) can lead to a
      spectrum of diseases including low grade inflammation (steatohepatitis or non-alcoholic
      steatohepatitis (NASH)), cirrhosis or liver failure.

      The current method used to diagnose liver dysfunction and failure is with percutaneous liver
      biopsy. This is painful and is not without risk, as the liver is a highly vascular organ.
      Even with ultrasound guidance, it carries a 1:1000 risk of serious adverse events (e.g.
      bleeding, infection, bowel perforation). As a result of these factors, liver biopsy is not
      used in all patients with suspected NAFLD/ NASH unless moderate to severe liver disease is
      presented or other liver disease need to be excluded. Various diagnostic pathways have
      arisen, but in the absence of a clearly non-invasive discriminatory test that can stratify
      normal liver, simple steatosis, steatohepatitis and cirrhosis, there is no standardised
      pathway.

      LiverMultiScan has been tested against liver biopsy and has been shown to be the first
      imaging test that can identify early liver disease and predict clinical outcomes accurately.
      LiverMultiScan has recently been CE-Marked and FDA-cleared, so is available for clinical use,
      but as a new test, it is not yet widely established in clinical practice. This study will
      utilise LiverMultiScan and see if it can be the basis of a viable diagnostic pathway in EU
      healthcare systems by adopting it in different EU countries, and determining the economic
      costs and benefits.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: To investigate whether the introduction of LiverMultiScan as a standardised diagnostic test for liver disease can prove a cost-effective method in different EU territories.
time frame: 1 year
description: Proportion of patients with suspected NAFLD incurring liver related hospital consultations and/or liver biopsies, from the date of randomisation to the end of the study follow-up.
measure: Patient satisfaction: questionnaire
time frame: 1 year
description: Patient feedback from patient satisfaction questionnaire, at baseline, and all follow-up visits to the end of the study.
measure: Certainty of diagnosis
time frame: 1 year
description: Certainty of diagnosis is defined as binary (yes/no vs. unlikely/probable) at baseline and all follow-up visits to the end of the study.
measure: Frequency of diagnosis
time frame: 1 year
description: Frequency of diagnosis is defined as binary (yes/probable vs. no/unlikely) at baseline and all follow-up visits to the end of the study.
measure: Time to diagnosis
time frame: 1 year
description: Time from randomisation to diagnosis by the physician, as recorded at final follow-up visit.
measure: Measure resource use
time frame: 1 year
description: Rates of liver related outpatient investigations/consultations/hospital admissions per 400 patients during the study.
measure: Cost effectiveness of LiverMultiScan
time frame: 1 year
description: Cost of LiverMultiScan based on randomised comparison.
measure: Personnel skills required for diagnosis
time frame: 1 year
description: Percentage of total consultations performed by a specialist, at each specialist medical category, from date of randomisation to end of study.
arm group label: Study Arm-LiverMultiScan
arm group type: Experimental
description: Patients will be scanned using the LiverMultiScan. Follow-up will be determined by the results of the scan.
arm group label: Control Arm
arm group type: No Intervention
description: Standard of care as per guidelines of the local centre
intervention type: Diagnostic Test
intervention name: LiverMultiScan
description: LiverMultiScan is an imaging technique which is able to identify early liver disease.
arm group label: Study Arm-LiverMultiScan
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Matthias Dollinger, MD
role: Principal Investigator
affiliation: University Hospital Ulm
last name: Dimitar Tonev, MD
role: Principal Investigator
affiliation: Perspectum Diagnostics
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Germany
country: Netherlands
country: Portugal
country: United Kingdom
citation: Banerjee R, Pavlides M, Tunnicliffe EM, Piechnik SK, Sarania N, Philips R, Collier JD, Booth JC, Schneider JE, Wang LM, Delaney DW, Fleming KA, Robson MD, Barnes E, Neubauer S. Multiparametric magnetic resonance for the non-invasive diagnosis of liver disease. J Hepatol. 2014 Jan;60(1):69-77. doi: 10.1016/j.jhep.2013.09.002. Epub 2013 Sep 12.
PMID: 24036007
citation: Pavlides M, Banerjee R, Sellwood J, Kelly CJ, Robson MD, Booth JC, Collier J, Neubauer S, Barnes E. Multiparametric magnetic resonance imaging predicts clinical outcomes in patients with chronic liver disease. J Hepatol. 2016 Feb;64(2):308-315. doi: 10.1016/j.jhep.2015.10.009. Epub 2015 Nov 10.
PMID: 26471505
responsible party type: Sponsor
mesh term: Fatty Liver
mesh term: Non-alcoholic Fatty Liver Disease
mesh term: Metabolic Syndrome
sharing ipd: No