<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/NCT01701687</url>
  </required_header>
  <id_info>
    <org_study_id>12050</org_study_id>
    <nct_id>NCT01701687</nct_id>
  </id_info>
  <brief_title>Biomarkers for the Prognosis of Decompensated Alcoholic Liver Disease</brief_title>
  <acronym>BANDED</acronym>
  <official_title>The Feasibility of Liver Biomarkers as Prognostic Markers in Decompensated Alcoholic Liver Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Nottingham</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute for Health Research, United Kingdom</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Nottingham</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Fibroscan is a non invasive imaging investigation which measures liver stiffness, known to&#xD;
      correlate well with liver scarring and cirrhosis on liver biopsy. Indocyanine green is an&#xD;
      inert dye which is purely extracted from the blood by liver cells, and is hence an excellent&#xD;
      marker of both liver cell function and overall liver blood flow. There is little data for&#xD;
      either of these biomarkers regarding outcomes in alcoholic liver disease. We aim to establish&#xD;
      the accuracy of these liver biomarkers in predicting important liver related outcomes (death,&#xD;
      transplantation and hospital readmission with cirrhosis related consequences) in patients&#xD;
      with severe (decompensated) alcoholic liver disease. Moreover, we will assess whether the&#xD;
      serial measurement of biomarkers has any impact on alcohol abstinence, motivation or quality&#xD;
      of life. Over an 18 month period, 125 consecutive hospital inpatients with decompensated&#xD;
      alcoholic liver disease will undergo baseline biomarker measurement, routine blood and urine&#xD;
      tests and qualitative questionnaires. These will be measured during their initial hospital&#xD;
      admission (0 months) with subsequent repeat measurement during follow up visits at 1, 2, 4&#xD;
      and 6 months. Each study visit time will be in the region of 30-40 minutes to complete these&#xD;
      investigations. The end of the study for individual patients will be patient death, liver&#xD;
      transplantation or 6 month from study enrolment; whichever occurs first.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single centre longitudinal cohort feasibility pilot study of patients with&#xD;
      decompensated alcoholic liver disease. We aim to recruit 125 consecutive patients with&#xD;
      decompensated alcoholic liver disease over an 18 month period. This number is based upon&#xD;
      approximately 10 admissions per month to acute liver services with decompensated alcoholic&#xD;
      liver disease and includes a presumed 20% dropout rate during follow up, giving a total&#xD;
      cohort of 100 patients. Patients will undergo a maximum of 6 months follow up following study&#xD;
      recruitment.&#xD;
&#xD;
      The purposes of this study are:&#xD;
&#xD;
        1. To assess the performance of diagnostic liver biomarkers (Indocyanine Green, Fibroscan&#xD;
           and blood and urinary biomarkers) in predicting mortality in decompensated alcoholic&#xD;
           liver disease.&#xD;
&#xD;
        2. To compare the diagnostic and prognostic end points of these biomarkers with existing&#xD;
           cirrhosis prognostic scoring systems (Child Pugh, MELD and UKELD).&#xD;
&#xD;
        3. To assess the performance of diagnostic biomarkers as a therapeutic aid to quality of&#xD;
           life and alcohol abstinence.&#xD;
&#xD;
      Potentially eligible patients i.e. adults with decompensated liver disease with alcohol as a&#xD;
      major co-factor, and acutely admitted secondary to sequelae of hepatic decompensation, will&#xD;
      be approached by an existing member of their clinical care team (The CI &amp; Co-Investigators&#xD;
      form part of this team). Any patient who decides to take part in the study will have a&#xD;
      baseline inpatient study visit either on their inpatient ward or to the NDDC Biomedical&#xD;
      Research Unit (BRU). Subsequent follow up visits will be to the BRU.&#xD;
&#xD;
      Inclusion Criteria:&#xD;
&#xD;
        -  Male or female patients 18-75 years of age&#xD;
&#xD;
        -  Diagnosis of cirrhosis based upon:&#xD;
&#xD;
             -  a) Histological confirmation&#xD;
&#xD;
             -  b) Combination of clinical and radiological criteria&#xD;
&#xD;
             -  c) Validated non invasive biomarker&#xD;
&#xD;
        -  Alcohol as the primary aetiology for liver cirrhosis&#xD;
&#xD;
        -  Hospital admission related to decompensated liver disease (e.g. ascites, varices,&#xD;
           sepsis, alcoholic hepatitis)&#xD;
&#xD;
        -  Active alcohol drinking prior to index hospital admission&#xD;
&#xD;
      Exclusion Criteria:&#xD;
&#xD;
        -  Grade 3 or 4 hepatic encephalopathy&#xD;
&#xD;
        -  Hepatocellular carcinoma&#xD;
&#xD;
        -  Active non hepatic malignancy&#xD;
&#xD;
        -  Known complete portal vein thrombosis&#xD;
&#xD;
        -  Alcohol abstinence at time of index hospital admission&#xD;
&#xD;
        -  Pregnancy&#xD;
&#xD;
        -  Active cardiac devices&#xD;
&#xD;
      The research visit will require measurement of ICG clearance, Fibroscan, blood tests, urine&#xD;
      tests and questionnaires. They will then be required to attend study visits at 1, 2, 4 and 6&#xD;
      months following the baseline study visit, after which study follow up will cease.&#xD;
&#xD;
      Patients will undergo study visits at the following intervals:&#xD;
&#xD;
        -  Baseline visit (study visit 0)&#xD;
&#xD;
        -  1 month (study visit 1)&#xD;
&#xD;
        -  2 months (study visit 2)&#xD;
&#xD;
        -  4 months (study visit 3)&#xD;
&#xD;
        -  6 months (study visit 4)&#xD;
&#xD;
      The following data will be collected for the purposes of this research project at the&#xD;
      baseline and subsequent study visits:&#xD;
&#xD;
        -  Collection of demography, anthropometry, drug history, smoking, alcohol intake, blood&#xD;
           pressure, full blood count, renal function, liver function, coagulation and serum&#xD;
           samples&#xD;
&#xD;
        -  Brief abdominal examination to detect presence of moderate to severe ascites (for the&#xD;
           purposes of Child Pugh score measurement)&#xD;
&#xD;
        -  ICG analysis&#xD;
&#xD;
        -  Transient elastography (Fibroscan)&#xD;
&#xD;
        -  Blood and urinary biomarkers (proteomics and metabonomics)&#xD;
&#xD;
        -  Chronic Liver Disease Quality of Life Questionnaire&#xD;
&#xD;
        -  Alcohol intake assessments (28 Day AUDIT tool)&#xD;
&#xD;
        -  Alcohol STAR tool for qualitative assessment (to assess the influence of Fibroscan/ICG&#xD;
           readings on motivation, beliefs and alcohol abstinence)&#xD;
&#xD;
      Demography and history are taken as part of normal clinical care. All patients will be&#xD;
      offered standard follow up from both outpatient hepatology clinic and hospital alcohol&#xD;
      liaison services throughout the period of study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">July 2015</completion_date>
  <primary_completion_date type="Actual">July 2015</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>Liver Related Death</measure>
    <time_frame>6 months</time_frame>
    <description>The proportion of deaths up to 6 months from the baseline visit directly attributable to consequences of cirrhosis</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Non-Liver related death</measure>
    <time_frame>6 months</time_frame>
    <description>Mortality unrelated to liver disease up to 6 months from baseline study visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital Readmission</measure>
    <time_frame>6 months</time_frame>
    <description>Hospital readmission secondary to complications of cirrhosis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alcohol abstinence</measure>
    <time_frame>6 months</time_frame>
    <description>Proportion of patients abstinent from alcohol at the 6 month timepoint</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">36</enrollment>
  <condition>Alcoholic Liver Diseases</condition>
  <condition>Decompensated Cirrhosis</condition>
  <arm_group>
    <arm_group_label>Decompensated Alcoholic Cirrhosis</arm_group_label>
    <description>Recruited patients will have diagnosed liver cirrhosis (histological, radiological or accepted clinical parameters)admitted with an episode of decompensation. Patients must still be drinking hazardous alcohol quantities (&gt;14 units for women, &gt;21 units for men) at study enrollment</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Serum, plasma and urine stored at -80 degrees centigrade under written patient consent&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Potentially eligible patients are adult patients with decompensated liver disease with&#xD;
        alcohol as a major co-factor, and acutely admitted secondary to sequelae of hepatic&#xD;
        decompensation. 100 patients will be recruited for baseline visit over an 30 month study&#xD;
        enrolment period, with a 6 month follow up period for all patients.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female patients 18-75 years of age&#xD;
&#xD;
          -  Diagnosis of cirrhosis based upon:&#xD;
&#xD;
               -  a) Histological confirmation&#xD;
&#xD;
               -  b) Combination of clinical and radiological criteria&#xD;
&#xD;
               -  c) Validated non invasive biomarker&#xD;
&#xD;
          -  Alcohol as the primary aetiology for liver cirrhosis&#xD;
&#xD;
          -  Hospital admission related to decompensated liver disease (e.g. ascites, varices,&#xD;
             sepsis, alcoholic hepatitis)&#xD;
&#xD;
          -  Active alcohol drinking prior to index hospital admission&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Grade 3 or 4 hepatic encephalopathy&#xD;
&#xD;
          -  Hepatocellular carcinoma&#xD;
&#xD;
          -  Active non hepatic malignancy&#xD;
&#xD;
          -  Known complete portal vein thrombosis&#xD;
&#xD;
          -  Alcohol abstinence at time of index hospital admission&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Active cardiac devices (e.g. cardiac pacemaker, implantable cardioverter&#xD;
             defibrillator)&#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>Neil Guha, MRCP, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Nottingham</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Nottingham University Hospitals NHS Trust</name>
      <address>
        <city>Nottingham</city>
        <state>Notts</state>
        <zip>NG7 2UH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>July 2015</verification_date>
  <study_first_submitted>October 3, 2012</study_first_submitted>
  <study_first_submitted_qc>October 3, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 5, 2012</study_first_posted>
  <last_update_submitted>July 31, 2015</last_update_submitted>
  <last_update_submitted_qc>July 31, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 3, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cirrhosis</keyword>
  <keyword>Alcoholic liver disease</keyword>
  <keyword>Decompensated liver cirrhosis</keyword>
  <keyword>Hazardous alcohol</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Cirrhosis</mesh_term>
    <mesh_term>Liver Diseases</mesh_term>
    <mesh_term>Liver Diseases, Alcoholic</mesh_term>
    <mesh_term>Fibrosis</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/NCT01701687
org study id: 12050
nct id: NCT01701687
lead sponsor: 
collaborator: 
has dmc: No
Fibroscan is a non invasive imaging investigation which measures liver stiffness, known to
      correlate well with liver scarring and cirrhosis on liver biopsy. Indocyanine green is an
      inert dye which is purely extracted from the blood by liver cells, and is hence an excellent
      marker of both liver cell function and overall liver blood flow. There is little data for
      either of these biomarkers regarding outcomes in alcoholic liver disease. We aim to establish
      the accuracy of these liver biomarkers in predicting important liver related outcomes (death,
      transplantation and hospital readmission with cirrhosis related consequences) in patients
      with severe (decompensated) alcoholic liver disease. Moreover, we will assess whether the
      serial measurement of biomarkers has any impact on alcohol abstinence, motivation or quality
      of life. Over an 18 month period, 125 consecutive hospital inpatients with decompensated
      alcoholic liver disease will undergo baseline biomarker measurement, routine blood and urine
      tests and qualitative questionnaires. These will be measured during their initial hospital
      admission (0 months) with subsequent repeat measurement during follow up visits at 1, 2, 4
      and 6 months. Each study visit time will be in the region of 30-40 minutes to complete these
      investigations. The end of the study for individual patients will be patient death, liver
      transplantation or 6 month from study enrolment; whichever occurs first.
This is a single centre longitudinal cohort feasibility pilot study of patients with
      decompensated alcoholic liver disease. We aim to recruit 125 consecutive patients with
      decompensated alcoholic liver disease over an 18 month period. This number is based upon
      approximately 10 admissions per month to acute liver services with decompensated alcoholic
      liver disease and includes a presumed 20% dropout rate during follow up, giving a total
      cohort of 100 patients. Patients will undergo a maximum of 6 months follow up following study
      recruitment.

      The purposes of this study are:

        1. To assess the performance of diagnostic liver biomarkers (Indocyanine Green, Fibroscan
           and blood and urinary biomarkers) in predicting mortality in decompensated alcoholic
           liver disease.

        2. To compare the diagnostic and prognostic end points of these biomarkers with existing
           cirrhosis prognostic scoring systems (Child Pugh, MELD and UKELD).

        3. To assess the performance of diagnostic biomarkers as a therapeutic aid to quality of
           life and alcohol abstinence.

      Potentially eligible patients i.e. adults with decompensated liver disease with alcohol as a
      major co-factor, and acutely admitted secondary to sequelae of hepatic decompensation, will
      be approached by an existing member of their clinical care team (The CI & Co-Investigators
      form part of this team). Any patient who decides to take part in the study will have a
      baseline inpatient study visit either on their inpatient ward or to the NDDC Biomedical
      Research Unit (BRU). Subsequent follow up visits will be to the BRU.

      Inclusion Criteria:

        -  Male or female patients 18-75 years of age

        -  Diagnosis of cirrhosis based upon:

             -  a) Histological confirmation

             -  b) Combination of clinical and radiological criteria

             -  c) Validated non invasive biomarker

        -  Alcohol as the primary aetiology for liver cirrhosis

        -  Hospital admission related to decompensated liver disease (e.g. ascites, varices,
           sepsis, alcoholic hepatitis)

        -  Active alcohol drinking prior to index hospital admission

      Exclusion Criteria:

        -  Grade 3 or 4 hepatic encephalopathy

        -  Hepatocellular carcinoma

        -  Active non hepatic malignancy

        -  Known complete portal vein thrombosis

        -  Alcohol abstinence at time of index hospital admission

        -  Pregnancy

        -  Active cardiac devices

      The research visit will require measurement of ICG clearance, Fibroscan, blood tests, urine
      tests and questionnaires. They will then be required to attend study visits at 1, 2, 4 and 6
      months following the baseline study visit, after which study follow up will cease.

      Patients will undergo study visits at the following intervals:

        -  Baseline visit (study visit 0)

        -  1 month (study visit 1)

        -  2 months (study visit 2)

        -  4 months (study visit 3)

        -  6 months (study visit 4)

      The following data will be collected for the purposes of this research project at the
      baseline and subsequent study visits:

        -  Collection of demography, anthropometry, drug history, smoking, alcohol intake, blood
           pressure, full blood count, renal function, liver function, coagulation and serum
           samples

        -  Brief abdominal examination to detect presence of moderate to severe ascites (for the
           purposes of Child Pugh score measurement)

        -  ICG analysis

        -  Transient elastography (Fibroscan)

        -  Blood and urinary biomarkers (proteomics and metabonomics)

        -  Chronic Liver Disease Quality of Life Questionnaire

        -  Alcohol intake assessments (28 Day AUDIT tool)

        -  Alcohol STAR tool for qualitative assessment (to assess the influence of Fibroscan/ICG
           readings on motivation, beliefs and alcohol abstinence)

      Demography and history are taken as part of normal clinical care. All patients will be
      offered standard follow up from both outpatient hepatology clinic and hospital alcohol
      liaison services throughout the period of study.
observational model: Cohort
time perspective: Prospective
measure: Liver Related Death
time frame: 6 months
description: The proportion of deaths up to 6 months from the baseline visit directly attributable to consequences of cirrhosis
measure: Non-Liver related death
time frame: 6 months
description: Mortality unrelated to liver disease up to 6 months from baseline study visit
measure: Hospital Readmission
time frame: 6 months
description: Hospital readmission secondary to complications of cirrhosis
measure: Alcohol abstinence
time frame: 6 months
description: Proportion of patients abstinent from alcohol at the 6 month timepoint
arm group label: Decompensated Alcoholic Cirrhosis
description: Recruited patients will have diagnosed liver cirrhosis (histological, radiological or accepted clinical parameters)admitted with an episode of decompensation. Patients must still be drinking hazardous alcohol quantities (>14 units for women, >21 units for men) at study enrollment
Serum, plasma and urine stored at -80 degrees centigrade under written patient consent
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Neil Guha, MRCP, PhD
role: Principal Investigator
affiliation: University of Nottingham
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Liver Cirrhosis
mesh term: Liver Diseases
mesh term: Liver Diseases, Alcoholic
mesh term: Fibrosis