<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/NCT01725035</url>
  </required_header>
  <id_info>
    <org_study_id>1008007192</org_study_id>
    <secondary_id>11CRP5620013</secondary_id>
    <secondary_id>1R01DK114504-01A1</secondary_id>
    <nct_id>NCT01725035</nct_id>
  </id_info>
  <brief_title>Hepatic De Novo Lipogenesis (DNL)in the Pathogenesis of Hepatic Steatosis in Obese Youth</brief_title>
  <acronym>DNL</acronym>
  <official_title>The Role of Hepatic De Novo Lipogenesis (DNL) in the Pathogenesis of Hepatic Steatosis in Obese Children and Adolescents</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yale University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>American Heart Association</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Yale University</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>
      Nonalcoholic Fatty Liver Disease (NAFLD) is becoming the most common cause of liver disease&#xD;
      in pediatrics, but little is known about its pathophysiology in children. While studies in&#xD;
      obese adults with hepatic steatosis have described an increased hepatic de novo lipogenesis&#xD;
      (DNL) depending on the diet, there are no studies exploring the mechanisms by which excess&#xD;
      hepatic triglycerides increases in obese youths, thus explaining the accompanying&#xD;
      dyslipidemia and the metabolic syndrome. The central hypothesis of this study is that hepatic&#xD;
      conversion of carbohydrates to lipid (DNL) is enhanced and associated with accumulation of&#xD;
      excess liver fat, dyslipidemia and hepatic insulin resistance in obese youths with hepatic&#xD;
      steatosis. The overall goal is to examine whether hepatic DNL is increased in obese youths&#xD;
      with steatosis compared to matched controls without steatosis.&#xD;
&#xD;
      Hypotheses: Hepatic conversion of carbohydrates to lipid (DNL) is enhanced and is associated&#xD;
      with accumulation of excess liver fat, dyslipidemia and hepatic insulin resistance in obese&#xD;
      youths with hepatic steatosis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this study obese youths, adolescents and young adults (12-30 years) will undergo MRI&#xD;
      (magnetic resonance imaging) measurement of liver lipid content to determine hepatic fat&#xD;
      content. They will undergo a sugary drink (75 grams of glucose and 25 grams of fructose)&#xD;
      challenge and Hepatic de novo lipogenesis will be determined as the incorporation of&#xD;
      deuterium, from deuterium labeled water (D2O), into plasma triglycerides. Subjects will&#xD;
      undergo a 6 hours study assessing de novo lipogenesis, an oral glucose tolerance test, dual&#xD;
      energy x-ray absorptiometry, magnetic resonance imaging, and Euglycemic-Hyperinsulinemic&#xD;
      Clamp.&#xD;
&#xD;
      This study record has been re-opened in 2019 and updated to reflect any changes having&#xD;
      remained open since its inception with the Yale University IRB and also having obtained&#xD;
      additional funding though NIDDK.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2010</start_date>
  <completion_date type="Actual">August 10, 2022</completion_date>
  <primary_completion_date type="Actual">August 10, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>de novo lipogenesis response to high carbohydrate meal in obese kids with fatty liver</measure>
    <time_frame>Study visit 3</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>de novo lipogenesis response to high carbohydrate meal in obese kids without fatty liver</measure>
    <time_frame>Study visit 3</time_frame>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">60</enrollment>
  <condition>Hepatic Steatosis</condition>
  <condition>Fatty Liver</condition>
  <arm_group>
    <arm_group_label>Fatty liver</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>Non Fatty liver</arm_group_label>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Serum&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The majority of the research subjects will be recruited from the Yale Pediatric Obesity&#xD;
        Clinic and the Endocrine Clinic. Following the oral glucose tolerance test (OGTT):normal&#xD;
        glucose tolerant if plasma glucose at two hours is &lt;140 mg/dl and impaired glucose tolerant&#xD;
        if plasma glucose is ≥140 mg/dl. All subjects must be in good general health, have a normal&#xD;
        medical history and physical exam, and have no endocrinopathies or other diseases that&#xD;
        might affect glucose metabolism. They will not be on any medications that are known to&#xD;
        alter glucose or insulin metabolism or certain psychiatric medications. Subjects determined&#xD;
        to be eligible will receive a MRI to determine Hepatic Fat Content. Subjects will agree to&#xD;
        genetic testing to determine genotype.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Cases will meet the following criteria:&#xD;
&#xD;
               -  BMI higher than 75th percentile&#xD;
&#xD;
               -  Hepatic fat fraction (the amount of fat into the liver) greater or equal than&#xD;
                  5.5%&#xD;
&#xD;
               -  Absence of any endocrinopathy&#xD;
&#xD;
               -  Absence of any therapy with medication known to alter glucose metabolism&#xD;
&#xD;
        Controls will meet the following criteria:&#xD;
&#xD;
          -  BMI higher than 75th percentile&#xD;
&#xD;
          -  Hepatic fat fraction (the amount of fat into the liver) lower than 5.5%&#xD;
&#xD;
          -  Absence of any endocrinopathy&#xD;
&#xD;
          -  Absence of any therapy with medication known to alter glucose metabolism&#xD;
&#xD;
          -  Absence of any therapy with medication known to alter glucose metabolism&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  BMI under the 75th percentile&#xD;
&#xD;
          -  Hepatic fat fraction (the amount of fat into the liver) less than 5.5%&#xD;
&#xD;
          -  Absence of any endocrinopathy&#xD;
&#xD;
          -  Any therapy with medication known to alter glucose metabolism&#xD;
&#xD;
        Controls will meet the following criteria:&#xD;
&#xD;
          -  BMI under the 75th percentile&#xD;
&#xD;
          -  Hepatic fat fraction (the amount of fat into the liver) greater than or equal to 5.5%&#xD;
&#xD;
          -  Any endocrinopathy&#xD;
&#xD;
          -  Any therapy with medication known to alter glucose metabolism&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>30 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sonia Caprio, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yale University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Nicola Santoro, M.D./Ph.D,</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yale University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Yale University</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06510</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>October 30, 2012</study_first_submitted>
  <study_first_submitted_qc>November 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 12, 2012</study_first_posted>
  <last_update_submitted>June 13, 2023</last_update_submitted>
  <last_update_submitted_qc>June 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>De Novo Lipogenesis</keyword>
  <keyword>Fatty Liver</keyword>
  <keyword>Hepatic Steatosis</keyword>
  <keyword>Gene variants</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fatty Liver</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/NCT01725035
org study id: 1008007192
secondary id: 11CRP5620013
secondary id: 1R01DK114504-01A1
nct id: NCT01725035
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Nonalcoholic Fatty Liver Disease (NAFLD) is becoming the most common cause of liver disease
      in pediatrics, but little is known about its pathophysiology in children. While studies in
      obese adults with hepatic steatosis have described an increased hepatic de novo lipogenesis
      (DNL) depending on the diet, there are no studies exploring the mechanisms by which excess
      hepatic triglycerides increases in obese youths, thus explaining the accompanying
      dyslipidemia and the metabolic syndrome. The central hypothesis of this study is that hepatic
      conversion of carbohydrates to lipid (DNL) is enhanced and associated with accumulation of
      excess liver fat, dyslipidemia and hepatic insulin resistance in obese youths with hepatic
      steatosis. The overall goal is to examine whether hepatic DNL is increased in obese youths
      with steatosis compared to matched controls without steatosis.

      Hypotheses: Hepatic conversion of carbohydrates to lipid (DNL) is enhanced and is associated
      with accumulation of excess liver fat, dyslipidemia and hepatic insulin resistance in obese
      youths with hepatic steatosis.
In this study obese youths, adolescents and young adults (12-30 years) will undergo MRI
      (magnetic resonance imaging) measurement of liver lipid content to determine hepatic fat
      content. They will undergo a sugary drink (75 grams of glucose and 25 grams of fructose)
      challenge and Hepatic de novo lipogenesis will be determined as the incorporation of
      deuterium, from deuterium labeled water (D2O), into plasma triglycerides. Subjects will
      undergo a 6 hours study assessing de novo lipogenesis, an oral glucose tolerance test, dual
      energy x-ray absorptiometry, magnetic resonance imaging, and Euglycemic-Hyperinsulinemic
      Clamp.

      This study record has been re-opened in 2019 and updated to reflect any changes having
      remained open since its inception with the Yale University IRB and also having obtained
      additional funding though NIDDK.
observational model: Case-Control
time perspective: Prospective
measure: de novo lipogenesis response to high carbohydrate meal in obese kids with fatty liver
time frame: Study visit 3
measure: de novo lipogenesis response to high carbohydrate meal in obese kids without fatty liver
time frame: Study visit 3
arm group label: Fatty liver
arm group label: Non Fatty liver
Serum
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 12 Years
maximum age: 30 Years
healthy volunteers: No
last name: Sonia Caprio, M.D.
role: Principal Investigator
affiliation: Yale University
last name: Nicola Santoro, M.D./Ph.D,
role: Principal Investigator
affiliation: Yale University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Fatty Liver