<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/NCT03260036</url>
  </required_header>
  <id_info>
    <org_study_id>FHNC-bariatric</org_study_id>
    <nct_id>NCT03260036</nct_id>
  </id_info>
  <brief_title>Hepatic Urea Nitrogen Handling in Patients With NASH</brief_title>
  <official_title>The Effect of Bariatric Surgery on Hepatic Urea Nitrogen Handling and Cognitive Functions in Patients With Severe Non-alcoholic Fatty Liver Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Aarhus</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Aarhus</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 aim of the project is to investigate the metabolic regulation of the hepatic urea&#xD;
      nitrogen handling and various cognitive functions measured by psychometric and&#xD;
      neurophysiological tests before and after bariatric surgery in patients with non-alcoholic&#xD;
      fatty liver disease (NAFLD).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      NAFLD is the most common cause of chronic liver disease in the western world affecting 10-30%&#xD;
      of the general population. It is strongly associated with the metabolic syndrome caused by&#xD;
      overweight and obesity. NAFLD is a spectrum of liver disease ranging from steatosis&#xD;
      (hepatocytic fat accumulation occurs without hepatocellular injury), to non-alcoholic&#xD;
      steatohepatitis (NASH) (steatosis is accompanied by inflammation and hepatocyte injury with&#xD;
      or without fibrosis) and to cirrhosis in patients that are not consuming excessive alcohol.&#xD;
      The prognosis of patients with simple steatosis appears benign whereas NASH often has a&#xD;
      progressive course with increased liver-related morbidity and mortality.&#xD;
&#xD;
      Patients with liver disease often have impairment of metabolic liver functions. The liver has&#xD;
      numerous functions, which are essential for maintenance of life e.g. urea synthesis. This&#xD;
      function is central in whole body nitrogen (N) homeostasis and removes ammonia, which is&#xD;
      produced during N conversion and is extremely toxic especially for brain functions.&#xD;
      Impairment of urea synthesis causes increased ammonia concentrations in the blood, which is&#xD;
      taken up by the brain and contributes to development of hepatic encephalopathy in patients&#xD;
      with liver disease. This condition is one of the most debilitating complications of liver&#xD;
      disease as it affects cognitive functions and with increasing severity also behaviour and&#xD;
      motor function. The mild stage (termed minimal hepatic encephalopathy) causes subtle&#xD;
      cognitive dysfunction, which can only be detected by means of special tests. The more severe&#xD;
      stages (manifest hepatic encephalopathy) are accompanied by manifest dysfunction of sleep&#xD;
      pattern and orientation eventually leading to liver coma. The condition is reversible and no&#xD;
      structural brain damage occurs.&#xD;
&#xD;
      We seek to investigate the consequences of bariatric surgery on liver and brain function with&#xD;
      a special focus on NASH patients. The investigations will comprise examination of the&#xD;
      capacity for urea synthesis and various psychometric and neurophysiological tests to evaluate&#xD;
      the patient's cognitive functions before and 18 months after surgery.&#xD;
&#xD;
      A liver biopsy will be availed at the time of surgical intervention and genetic and&#xD;
      functional characterization of urea cycle enzymes will be performed to correlate with&#xD;
      histological scores, clinical disease staging and ammonia/capacity for urea synthesis. A&#xD;
      further liver biopsy will be performed after 18 months to determine if there has been any&#xD;
      change in NAFLD disease stage and urea cycle enzymes after intervention.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 21, 2017</start_date>
  <completion_date type="Anticipated">August 21, 2022</completion_date>
  <primary_completion_date type="Anticipated">August 21, 2022</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>Changes in Functional Hepatic Nitrogen Clearance (FHNC)</measure>
    <time_frame>Baseline and 18 months</time_frame>
    <description>FHNC is a validated method for assessing the conversion of amino-nitrogen to urea-nitrogen by the liver</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Urea cycle enzymes (protein and gene level)</measure>
    <time_frame>Baseline and 18 months</time_frame>
    <description>Examined in liver biopsy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in The Portosystemic Encephalopathy Syndrome-Test</measure>
    <time_frame>Baseline and 18 months</time_frame>
    <description>To evaluate changes in the patient's cognitive functions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Continuous Reaction Time Test</measure>
    <time_frame>Baseline and 18 months</time_frame>
    <description>To evaluate changes in the patient's cognitive functions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Critical Flicker Frequency</measure>
    <time_frame>Baseline and 18 months</time_frame>
    <description>To evaluate changes in the patient's cognitive functions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in EEG</measure>
    <time_frame>Baseline and 18 months</time_frame>
    <description>To evaluate potential changes in the patient's EEG</description>
  </secondary_outcome>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Non-Alcoholic Fatty Liver Disease</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Liver tissue Blood&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Obese patients referred for bariatric surgery&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Referred for bariatric surgery (BMI &gt; 40 kg/m2 or BMI &gt; 35 kg/m2 and obesity-related&#xD;
             complications&#xD;
&#xD;
          -  Steatosis on ultrasound (US)&#xD;
&#xD;
          -  Alcohol intake &lt; 40g/day&#xD;
&#xD;
          -  Exclusion of other liver diseases&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Chronic inflammatory diseases&#xD;
&#xD;
          -  Acute severe bacterial infection (sepsis, pneumonia, urinary tract infection etc.)&#xD;
&#xD;
          -  Cancer&#xD;
&#xD;
          -  Neurological diseases&#xD;
&#xD;
          -  Prednisolone treatment within the last 8 weeks&#xD;
&#xD;
          -  Pregnancy&#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>Karen Louise Thomsen, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Aarhus University Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Karen Louise Thomsen, MD, PhD</last_name>
    <phone>+45 78463892</phone>
    <email>karethom@rm.dk</email>
  </overall_contact>
  <location>
    <facility>
      <name>Department of Hepatology and Gastroenterology, Aarhus University Hospital</name>
      <address>
        <city>Aarhus</city>
        <zip>8000</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Karen Louise Thomsen, MD, PhD</last_name>
      <phone>+45 78463892</phone>
      <email>karethom@rm.dk</email>
    </contact>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>August 16, 2017</study_first_submitted>
  <study_first_submitted_qc>August 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 24, 2017</study_first_posted>
  <last_update_submitted>March 27, 2020</last_update_submitted>
  <last_update_submitted_qc>March 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 30, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Urea synthesis</keyword>
  <keyword>Ammonia</keyword>
  <keyword>Bariatric surgery</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Diseases</mesh_term>
    <mesh_term>Fatty Liver</mesh_term>
    <mesh_term>Non-alcoholic Fatty Liver Disease</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/NCT03260036
org study id: FHNC-bariatric
nct id: NCT03260036
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The aim of the project is to investigate the metabolic regulation of the hepatic urea
      nitrogen handling and various cognitive functions measured by psychometric and
      neurophysiological tests before and after bariatric surgery in patients with non-alcoholic
      fatty liver disease (NAFLD).
NAFLD is the most common cause of chronic liver disease in the western world affecting 10-30%
      of the general population. It is strongly associated with the metabolic syndrome caused by
      overweight and obesity. NAFLD is a spectrum of liver disease ranging from steatosis
      (hepatocytic fat accumulation occurs without hepatocellular injury), to non-alcoholic
      steatohepatitis (NASH) (steatosis is accompanied by inflammation and hepatocyte injury with
      or without fibrosis) and to cirrhosis in patients that are not consuming excessive alcohol.
      The prognosis of patients with simple steatosis appears benign whereas NASH often has a
      progressive course with increased liver-related morbidity and mortality.

      Patients with liver disease often have impairment of metabolic liver functions. The liver has
      numerous functions, which are essential for maintenance of life e.g. urea synthesis. This
      function is central in whole body nitrogen (N) homeostasis and removes ammonia, which is
      produced during N conversion and is extremely toxic especially for brain functions.
      Impairment of urea synthesis causes increased ammonia concentrations in the blood, which is
      taken up by the brain and contributes to development of hepatic encephalopathy in patients
      with liver disease. This condition is one of the most debilitating complications of liver
      disease as it affects cognitive functions and with increasing severity also behaviour and
      motor function. The mild stage (termed minimal hepatic encephalopathy) causes subtle
      cognitive dysfunction, which can only be detected by means of special tests. The more severe
      stages (manifest hepatic encephalopathy) are accompanied by manifest dysfunction of sleep
      pattern and orientation eventually leading to liver coma. The condition is reversible and no
      structural brain damage occurs.

      We seek to investigate the consequences of bariatric surgery on liver and brain function with
      a special focus on NASH patients. The investigations will comprise examination of the
      capacity for urea synthesis and various psychometric and neurophysiological tests to evaluate
      the patient's cognitive functions before and 18 months after surgery.

      A liver biopsy will be availed at the time of surgical intervention and genetic and
      functional characterization of urea cycle enzymes will be performed to correlate with
      histological scores, clinical disease staging and ammonia/capacity for urea synthesis. A
      further liver biopsy will be performed after 18 months to determine if there has been any
      change in NAFLD disease stage and urea cycle enzymes after intervention.
observational model: Cohort
time perspective: Prospective
measure: Changes in Functional Hepatic Nitrogen Clearance (FHNC)
time frame: Baseline and 18 months
description: FHNC is a validated method for assessing the conversion of amino-nitrogen to urea-nitrogen by the liver
measure: Urea cycle enzymes (protein and gene level)
time frame: Baseline and 18 months
description: Examined in liver biopsy
measure: Changes in The Portosystemic Encephalopathy Syndrome-Test
time frame: Baseline and 18 months
description: To evaluate changes in the patient's cognitive functions
measure: Changes in Continuous Reaction Time Test
time frame: Baseline and 18 months
description: To evaluate changes in the patient's cognitive functions
measure: Changes in Critical Flicker Frequency
time frame: Baseline and 18 months
description: To evaluate changes in the patient's cognitive functions
measure: Changes in EEG
time frame: Baseline and 18 months
description: To evaluate potential changes in the patient's EEG
Liver tissue Blood
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Karen Louise Thomsen, MD, PhD
role: Principal Investigator
affiliation: Aarhus University Hospital
last name: Karen Louise Thomsen, MD, PhD
phone: +45 78463892
email: karethom@rm.dk
facility: 
status: Recruiting
contact: 
country: Denmark
responsible party type: Sponsor
mesh term: Liver Diseases
mesh term: Fatty Liver
mesh term: Non-alcoholic Fatty Liver Disease
sharing ipd: No