<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/NCT02994459</url>
  </required_header>
  <id_info>
    <org_study_id>201610005</org_study_id>
    <nct_id>NCT02994459</nct_id>
  </id_info>
  <brief_title>Study of Fat Tissue's Ability to Take up Sugar in the Obese Population</brief_title>
  <acronym>ATGD</acronym>
  <official_title>Adipose Tissue Glucose Uptake in Obesity (ATGD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Washington University School of Medicine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      People who are obese often have insulin resistance (inability of insulin to properly control&#xD;
      blood sugar) and high blood sugar. However, not all people with obesity have this problem.&#xD;
      About one-third of people with obesity have normal sugar metabolism (the way your body uses&#xD;
      sugar). Similarly, not all people who are lean are also metabolically healthy and a subset of&#xD;
      people who are lean are referred to as metabolically abnormal lean (MAL) or metabolically&#xD;
      obese lean because they have the abnormalities in glucose metabolism typically associated&#xD;
      with obesity. The reasons why some people with obesity have a problem with blood sugar&#xD;
      control and others do not are not entirely clear. It is thought that impaired muscle sugar&#xD;
      uptake is the main problem related to high blood sugar in people with obesity. However,&#xD;
      adipose tissue (fat tissue) also consumes a substantial amount of blood sugar. Therefore, it&#xD;
      is unclear whether muscle or adipose tissue (fat tissue) are primarily responsible for&#xD;
      altered blood sugar concentrations in persons with metabolically abnormal obesity (MAO)&#xD;
      (those with insulin resistance), compared to those with metabolically normal (healthy)&#xD;
      obesity (MNO), or whether &quot;healthy&quot; adipose tissue (fat tissue) expansion in MNO people&#xD;
      compared with lean people provides a vessel for blood sugar removal that helps maintain&#xD;
      normal blood sugar concentration.&#xD;
&#xD;
      Accordingly, the investigators will determine the amount of sugar that is taken up by the&#xD;
      body and in the cells of adipose tissue (fat tissue) and muscle by infusing labeled sugar&#xD;
      into the blood and looking at its disappearance from blood and appearance in adipose tissue&#xD;
      (fat tissue) and muscle. The investigators will also determine how well insulin, a hormone&#xD;
      that controls blood sugar, turns on signals that stimulate sugar uptake in fat and muscle&#xD;
      cells. These studies will be done after an overnight fast and during an infusion of sugar and&#xD;
      insulin (hyperinsulinemic-euglycemic clamp), in sex- and age-matched people who are insulin&#xD;
      resistant and insulin sensitive. People with obesity will also be invited to complete a ~10%&#xD;
      diet-induced weight loss program and will be studied again after they have achieved the&#xD;
      weight loss goal. A group of sex- and age-matched metabolically normal lean participants will&#xD;
      serve as control group. An attempt will be made to also study a group of sex- and age-matched&#xD;
      metabolically abnormal lean participants.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 1, 2017</start_date>
  <completion_date type="Anticipated">January 2027</completion_date>
  <primary_completion_date type="Anticipated">January 2027</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>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Contribution of subcutaneous adipose tissue glucose uptake to whole-body glucose disposal in people who are insulin sensitive or insulin resistant (defined as insulin-mediated glucose disposal rate)</measure>
    <time_frame>Baseline</time_frame>
    <description>Comparison of whole body and total adipose tissue glucose disposal rate assessed by using stable isotope labeled glucose tracer infusion in conjunction with dynamic PET imaging</description>
  </primary_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Anticipated">90</enrollment>
  <condition>Glucose Metabolism Disorders</condition>
  <arm_group>
    <arm_group_label>Metabolically Normal Obese (likely insulin sensitive)</arm_group_label>
    <description>i) BMI ≥30.0 but &lt;45.0 kg/m2; maximum body circumference &lt;165 cm to ensure subjects fit into the PET/CT and MR scanners; iii) fasting blood glucose: &lt;100 mg/dl; iv) blood glucose 2 h after an OGTT: &lt;140 mg/dl; v) HbA1c &lt;5.7 %; vi) fasting insulin: &lt;20 µU/mL.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Metabolically Abnormal Obese (likely insulin resistant)</arm_group_label>
    <description>i) BMI ≥30.0 but &lt;45.0 kg/m2; maximum body circumference &lt;165 cm to ensure subjects fit into the PET/CT and MR scanners; iii) fasting blood glucose: ≥100 mg/dl or blood glucose 2 h after an OGTT: ≥140 or fasting insulin: &gt;20 µU/mL.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Metabolically Normal Lean</arm_group_label>
    <description>i) BMI ≥18.5 but &lt;25.0 kg/m2; ii) maximum body circumference &lt;165 cm to ensure subjects fit into the PET/CT and MR scanners; iii) fasting blood glucose: &lt;100 mg/dl; iv) blood glucose 2 h after an OGTT: &lt;140 mg/dl; v) HbA1c &lt;5.7 %; vi) fasting insulin: &lt;20 µU/mL.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Metabolically Abnormal Lean</arm_group_label>
    <description>i) BMI ≥18.5 but &lt;25.0 kg/m2; ii) maximum body circumference &lt;165 cm to ensure subjects fit into the PET/CT and MR scanners; iii) iii) fasting blood glucose: ≥100 mg/dl or blood glucose 2 h after an OGTT: ≥140 or fasting insulin: &gt;20 µU/mL.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Weight Loss</intervention_name>
    <description>Diet-induced weight loss (obese only)</description>
    <arm_group_label>Metabolically Abnormal Obese (likely insulin resistant)</arm_group_label>
    <arm_group_label>Metabolically Normal Obese (likely insulin sensitive)</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood and adipose/muscle tissue samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The investigators plan to study a total of 45 men and women of all races and ethnic groups:&#xD;
        15 MAO (metabolically abnormal obese, likely insulin resistant), 15 MNO (metabolically&#xD;
        normal obese, likely insulin sensitive), and 15 lean. All three groups will be balanced&#xD;
        with regards to sex and race/ethnicity distribution, and the two obese groups will also be&#xD;
        matched on percent total body fat. They will also attempt to recruit 15 metabolically&#xD;
        abnormal lean participants.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        All subjects&#xD;
&#xD;
          -  Age: greater than or equal to 18 years but &lt;65 years&#xD;
&#xD;
          -  Weight stable (i.e., ±2 kg for at least 3 months)&#xD;
&#xD;
          -  Sedentary (less than 1 hour of structured exercise per week)&#xD;
&#xD;
          -  No evidence of significant organ system dysfunction or disease (e.g., diabetes,&#xD;
             impaired kidney function, cancer, etc.)&#xD;
&#xD;
        In addition, subjects must fulfill all of the following inclusion criteria.&#xD;
&#xD;
        Metabolically Normal Lean&#xD;
&#xD;
          -  BMI greater than or equal to 18.5 but &lt;25.0 kg/m2&#xD;
&#xD;
          -  Fasting blood glucose: &lt;100 mg/dl&#xD;
&#xD;
          -  Blood glucose 2 h after an OGTT: &lt;140 mg/dl&#xD;
&#xD;
          -  HbA1c &lt;5.7 %.&#xD;
&#xD;
        Metabolically Normal Obese, likely insulin sensitive&#xD;
&#xD;
          -  BMI greater than or equal to 30.0 but &lt;45.0 kg/m2&#xD;
&#xD;
          -  Fasting blood glucose: &lt;100 mg/dl&#xD;
&#xD;
          -  Fasting insulin: &lt;20 mU/l&#xD;
&#xD;
          -  Blood glucose 2 h after an OGTT: &lt;140 mg/dl&#xD;
&#xD;
          -  HbA1c &lt;5.7 %.&#xD;
&#xD;
        Metabolically Abnormal Obese, likely insulin resistant&#xD;
&#xD;
          -  BMI greater than or equal to 30.0 but &lt;45.0 kg/m2&#xD;
&#xD;
          -  Fasting blood glucose ≥100 mg/dl or blood glucose 2 h after an OGTT ≥140 mg/dl or&#xD;
             fasting insulin &gt;20 µU/mL or HbA1c &gt;5.7 %.&#xD;
&#xD;
        Metabolically Abnormal Lean&#xD;
&#xD;
          -  BMI greater than or equal to 18.5 but &lt;25.0 kg/m2&#xD;
&#xD;
          -  Fasting blood glucose ≥100 mg/dl or blood glucose 2 h after an OGTT ≥140 mg/dl or&#xD;
             fasting insulin &gt;20 µU/mL or HbA1c &gt;5.7 %.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>64 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bettina Mittendorfer, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Washington University School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>December 9, 2016</study_first_submitted>
  <study_first_submitted_qc>December 12, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 15, 2016</study_first_posted>
  <last_update_submitted>May 26, 2023</last_update_submitted>
  <last_update_submitted_qc>May 26, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 30, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Washington University School of Medicine</investigator_affiliation>
    <investigator_full_name>Bettina Mittendorfer</investigator_full_name>
    <investigator_title>PhD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metabolic Diseases</mesh_term>
    <mesh_term>Glucose Metabolism Disorders</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The investigators do not currently anticipate to share IPD, but will do so upon request.</ipd_description>
  </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/NCT02994459
org study id: 201610005
nct id: NCT02994459
lead sponsor: 
has dmc: Yes
People who are obese often have insulin resistance (inability of insulin to properly control
      blood sugar) and high blood sugar. However, not all people with obesity have this problem.
      About one-third of people with obesity have normal sugar metabolism (the way your body uses
      sugar). Similarly, not all people who are lean are also metabolically healthy and a subset of
      people who are lean are referred to as metabolically abnormal lean (MAL) or metabolically
      obese lean because they have the abnormalities in glucose metabolism typically associated
      with obesity. The reasons why some people with obesity have a problem with blood sugar
      control and others do not are not entirely clear. It is thought that impaired muscle sugar
      uptake is the main problem related to high blood sugar in people with obesity. However,
      adipose tissue (fat tissue) also consumes a substantial amount of blood sugar. Therefore, it
      is unclear whether muscle or adipose tissue (fat tissue) are primarily responsible for
      altered blood sugar concentrations in persons with metabolically abnormal obesity (MAO)
      (those with insulin resistance), compared to those with metabolically normal (healthy)
      obesity (MNO), or whether "healthy" adipose tissue (fat tissue) expansion in MNO people
      compared with lean people provides a vessel for blood sugar removal that helps maintain
      normal blood sugar concentration.

      Accordingly, the investigators will determine the amount of sugar that is taken up by the
      body and in the cells of adipose tissue (fat tissue) and muscle by infusing labeled sugar
      into the blood and looking at its disappearance from blood and appearance in adipose tissue
      (fat tissue) and muscle. The investigators will also determine how well insulin, a hormone
      that controls blood sugar, turns on signals that stimulate sugar uptake in fat and muscle
      cells. These studies will be done after an overnight fast and during an infusion of sugar and
      insulin (hyperinsulinemic-euglycemic clamp), in sex- and age-matched people who are insulin
      resistant and insulin sensitive. People with obesity will also be invited to complete a ~10%
      diet-induced weight loss program and will be studied again after they have achieved the
      weight loss goal. A group of sex- and age-matched metabolically normal lean participants will
      serve as control group. An attempt will be made to also study a group of sex- and age-matched
      metabolically abnormal lean participants.
observational model: Cohort
time perspective: Cross-Sectional
measure: Contribution of subcutaneous adipose tissue glucose uptake to whole-body glucose disposal in people who are insulin sensitive or insulin resistant (defined as insulin-mediated glucose disposal rate)
time frame: Baseline
description: Comparison of whole body and total adipose tissue glucose disposal rate assessed by using stable isotope labeled glucose tracer infusion in conjunction with dynamic PET imaging
arm group label: Metabolically Normal Obese (likely insulin sensitive)
description: i) BMI ≥30.0 but <45.0 kg/m2; maximum body circumference <165 cm to ensure subjects fit into the PET/CT and MR scanners; iii) fasting blood glucose: <100 mg/dl; iv) blood glucose 2 h after an OGTT: <140 mg/dl; v) HbA1c <5.7 %; vi) fasting insulin: <20 µU/mL.
arm group label: Metabolically Abnormal Obese (likely insulin resistant)
description: i) BMI ≥30.0 but <45.0 kg/m2; maximum body circumference <165 cm to ensure subjects fit into the PET/CT and MR scanners; iii) fasting blood glucose: ≥100 mg/dl or blood glucose 2 h after an OGTT: ≥140 or fasting insulin: >20 µU/mL.
arm group label: Metabolically Normal Lean
description: i) BMI ≥18.5 but <25.0 kg/m2; ii) maximum body circumference <165 cm to ensure subjects fit into the PET/CT and MR scanners; iii) fasting blood glucose: <100 mg/dl; iv) blood glucose 2 h after an OGTT: <140 mg/dl; v) HbA1c <5.7 %; vi) fasting insulin: <20 µU/mL.
arm group label: Metabolically Abnormal Lean
description: i) BMI ≥18.5 but <25.0 kg/m2; ii) maximum body circumference <165 cm to ensure subjects fit into the PET/CT and MR scanners; iii) iii) fasting blood glucose: ≥100 mg/dl or blood glucose 2 h after an OGTT: ≥140 or fasting insulin: >20 µU/mL.
intervention type: Other
intervention name: Weight Loss
description: Diet-induced weight loss (obese only)
arm group label: Metabolically Abnormal Obese (likely insulin resistant)
arm group label: Metabolically Normal Obese (likely insulin sensitive)
Blood and adipose/muscle tissue samples
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 64 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Bettina Mittendorfer, PhD
role: Principal Investigator
affiliation: Washington University School of Medicine
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Washington University School of Medicine
investigator full name: Bettina Mittendorfer
investigator title: PhD
mesh term: Metabolic Diseases
mesh term: Glucose Metabolism Disorders
sharing ipd: Yes
ipd description: The investigators do not currently anticipate to share IPD, but will do so upon request.