<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/NCT02263677</url>
  </required_header>
  <id_info>
    <org_study_id>MERCK-9938</org_study_id>
    <nct_id>NCT02263677</nct_id>
  </id_info>
  <brief_title>Evaluation of the DPP-4 Inhibitor Sitagliptin in the Treatment of Non-Alcoholic Fatty Liver Disease Using MRI</brief_title>
  <official_title>Pilot Project Evaluation of the DPP-4 Inhibitor Sitagliptin in the Treatment of Non-Alcoholic Fatty Liver Disease Using MRI</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Missouri-Columbia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Missouri-Columbia</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Participants will be persons with type 2 diabetes who are likely to have fatty liver disease.&#xD;
      The investigators think that this medication will reduce fatty liver.&#xD;
&#xD;
      The investigators will use an MRS (a non invasive method using magnets) to evaluate liver fat&#xD;
      before and after subjects take a diabetes medication. The investigators will also collect a&#xD;
      small amount of blood to measure liver, kidney and hormone functions. This will be done 4&#xD;
      times. Also, at the time of the subject gets their first dose of medication they will have a&#xD;
      DEXA (low exposure x-ray often used in clinical practice to measure bone density and body&#xD;
      composition).&#xD;
&#xD;
      The goal of all of these studies is to determine whether the study drug lowers liver fat.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Non-alcoholic fatty liver disease (NAFLD) and its progression to non-alcoholic&#xD;
      steatohepatitis (NASH) and finally cirrhosis is rapidly becoming the leading cause of liver&#xD;
      injury and end stage liver disease, particularly in industrialized countries. Though several&#xD;
      pharmacologic agents (i.e. metformin, pioglitazone and others) have been suggested to have&#xD;
      benefit in reducing the progression of this disease, none is approved for use.&#xD;
&#xD;
      The causes of NAFLD and NASH are unknown, though visceral obesity, metabolic syndrome and&#xD;
      type 2 diabetes are recognized co-existent risk factors. Recent evidence has linked NAFLD to&#xD;
      elevated dipeptidyl peptidase-4 (DPP-4). DPP-4 levels in the plasma and livers of persons&#xD;
      with NAFLD are elevated and correlate with elevations in liver enzymes, though not with&#xD;
      markers of insulin resistance alone.&#xD;
&#xD;
      It has been proposed that increased DPP-4 activity in combination with decreased PPAR&#xD;
      signaling stimulates the inflammatory response that leads to liver fibrosis in the transition&#xD;
      of NASH to cirrhosis. Debate exists as to whether the effect of DPP-4 in the liver is via its&#xD;
      effect on the intestinal hormones or its direct effects on liver tissue. Indeed some studies&#xD;
      have found reductions in liver fat with administration of GLP-1 agonists in animal models of&#xD;
      obesity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Technical difficulties have caused this study to be terminated&#xD;
  </why_stopped>
  <start_date>March 2014</start_date>
  <completion_date type="Actual">January 2016</completion_date>
  <primary_completion_date type="Anticipated">December 2015</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Liver steatosis</measure>
    <time_frame>baseline and Six months</time_frame>
    <description>Steatosis measured by Magnetic Resonance Spectroscopy</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Type 2 Diabetes</condition>
  <condition>Non-alcoholic Fatty Liver Disease</condition>
  <arm_group>
    <arm_group_label>Sitagliptin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>60 day supply of 100mg Sitagliptin</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sitagliptin</intervention_name>
    <description>60 day supply of 100mg Sitagliptin. The investigators will use an MRS (a non invasive method using magnets) to evaluate liver fat before and after subjects take a diabetes medication. The investigators will also collect a small amount of blood to measure liver, kidney and hormone functions. This will be done 4 times. Also, at the time of the subject gets their first dose of medication they will have a DEXA (low exposure x-ray often used in clinical practice to measure bone density and body composition).</description>
    <arm_group_label>Sitagliptin</arm_group_label>
    <other_name>Januvia</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Type 2 diabetes mellitus with hemoglobin A1c above 6.5%.&#xD;
&#xD;
          2. Waist circumference over 40 inches in a male or 35 inches in a female or BMI greater&#xD;
             than 30.&#xD;
&#xD;
          3. Age between 18 and 70 years.&#xD;
&#xD;
          4. Stable on maximum tolerated dose of metformin for at least 3 months prior to&#xD;
             enrollment.&#xD;
&#xD;
          5. Sedentary (less than 30 minutes per week of structured activity) and weight stable (2%&#xD;
             body weight in past 6 months).&#xD;
&#xD;
          6. Metabolic syndrome based on NCEP ATP-3 guidelines with diabetes accepted as the&#xD;
             glycemic component.&#xD;
&#xD;
          7. For women: at least 2 years postmenopausal, surgically sterile, or using an acceptable&#xD;
             contraceptive regimen to include OCP, IUD, double barrier, depo-provera, or&#xD;
             subcutaneous progestin implant and negative urine pregnancy test at trial start.&#xD;
&#xD;
          8. For men: surgically sterile or agreement that any female partner meet criteria of 7.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnancy, breast feeding, or planning to become pregnant during the study period.&#xD;
&#xD;
          2. GFR less than 60mL per minute per meter squared.&#xD;
&#xD;
          3. Any medical condition expected to be terminal within one year.&#xD;
&#xD;
          4. Cirrhosis of any cause or liver disease due to auto-immune, infectious or alcohol&#xD;
             induced hepatitis.&#xD;
&#xD;
          5. Active mental illness or other condition which in the opinion of the investigator&#xD;
             would prevent informed consent or compliance with study protocol.&#xD;
&#xD;
          6. Use of PPAR agonist within six months prior to enrollment.&#xD;
&#xD;
          7. Daily insulin use.&#xD;
&#xD;
          8. Allergy or intolerance of sitagliptin or other DPP-4 inhibitor.&#xD;
&#xD;
          9. Use of DPP-4 inhibitor, bile acid sequesterant, or weight loss medications within&#xD;
             three months prior to enrollment.&#xD;
&#xD;
         10. Significant alcohol use defined as greater than 21 standard servings of alcohol&#xD;
             (10gms) per week for men and greater than 14 for women.&#xD;
&#xD;
         11. History of bariatric surgery or planned bariatric surgery during the study period.&#xD;
&#xD;
         12. Weight, girth, or other factor preventing MRI scanning.&#xD;
&#xD;
         13. Receipt of another study drug within 30 days of screening.&#xD;
&#xD;
         14. Unable to receive a DEXA scan due to participating in research study or medical&#xD;
             procedure involving ionizing radiation exposure equivalent to a chest x-ray or greater&#xD;
             in the past 12 months.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael Gardner, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Missouri-Columbia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Missouri-Columbia: Diabetes Center</name>
      <address>
        <city>Columbia</city>
        <state>Missouri</state>
        <zip>65212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2016</verification_date>
  <study_first_submitted>October 1, 2014</study_first_submitted>
  <study_first_submitted_qc>October 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 13, 2014</study_first_posted>
  <last_update_submitted>October 3, 2016</last_update_submitted>
  <last_update_submitted_qc>October 3, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 5, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>diabetes</keyword>
  <keyword>fatty liver</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sitagliptin Phosphate</mesh_term>
  </intervention_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/NCT02263677
org study id: MERCK-9938
nct id: NCT02263677
lead sponsor: 
has dmc: No
Participants will be persons with type 2 diabetes who are likely to have fatty liver disease.
      The investigators think that this medication will reduce fatty liver.

      The investigators will use an MRS (a non invasive method using magnets) to evaluate liver fat
      before and after subjects take a diabetes medication. The investigators will also collect a
      small amount of blood to measure liver, kidney and hormone functions. This will be done 4
      times. Also, at the time of the subject gets their first dose of medication they will have a
      DEXA (low exposure x-ray often used in clinical practice to measure bone density and body
      composition).

      The goal of all of these studies is to determine whether the study drug lowers liver fat.
Non-alcoholic fatty liver disease (NAFLD) and its progression to non-alcoholic
      steatohepatitis (NASH) and finally cirrhosis is rapidly becoming the leading cause of liver
      injury and end stage liver disease, particularly in industrialized countries. Though several
      pharmacologic agents (i.e. metformin, pioglitazone and others) have been suggested to have
      benefit in reducing the progression of this disease, none is approved for use.

      The causes of NAFLD and NASH are unknown, though visceral obesity, metabolic syndrome and
      type 2 diabetes are recognized co-existent risk factors. Recent evidence has linked NAFLD to
      elevated dipeptidyl peptidase-4 (DPP-4). DPP-4 levels in the plasma and livers of persons
      with NAFLD are elevated and correlate with elevations in liver enzymes, though not with
      markers of insulin resistance alone.

      It has been proposed that increased DPP-4 activity in combination with decreased PPAR
      signaling stimulates the inflammatory response that leads to liver fibrosis in the transition
      of NASH to cirrhosis. Debate exists as to whether the effect of DPP-4 in the liver is via its
      effect on the intestinal hormones or its direct effects on liver tissue. Indeed some studies
      have found reductions in liver fat with administration of GLP-1 agonists in animal models of
      obesity.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in Liver steatosis
time frame: baseline and Six months
description: Steatosis measured by Magnetic Resonance Spectroscopy
arm group label: Sitagliptin
arm group type: Experimental
description: 60 day supply of 100mg Sitagliptin
intervention type: Drug
intervention name: Sitagliptin
description: 60 day supply of 100mg Sitagliptin. The investigators will use an MRS (a non invasive method using magnets) to evaluate liver fat before and after subjects take a diabetes medication. The investigators will also collect a small amount of blood to measure liver, kidney and hormone functions. This will be done 4 times. Also, at the time of the subject gets their first dose of medication they will have a DEXA (low exposure x-ray often used in clinical practice to measure bone density and body composition).
arm group label: Sitagliptin
other name: Januvia
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Michael Gardner, MD
role: Principal Investigator
affiliation: University of Missouri-Columbia
facility: 
country: United States
responsible party type: Sponsor
mesh term: Liver Diseases
mesh term: Fatty Liver
mesh term: Non-alcoholic Fatty Liver Disease
mesh term: Sitagliptin Phosphate
sharing ipd: No