<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/NCT02196051</url>
  </required_header>
  <id_info>
    <org_study_id>0710003207</org_study_id>
    <secondary_id>R56AG023686</secondary_id>
    <nct_id>NCT02196051</nct_id>
  </id_info>
  <brief_title>Basic Research Study to Examine the Relation Between Muscle Insulin Resistance and Lipid Production in the Liver.</brief_title>
  <official_title>Lipid and Carbohydrate Metabolism: Effects of Exercise</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yale University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Aging (NIA)</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>
      The purpose of this study is to examine the pathophysiology of insulin resistance and the&#xD;
      relation to the metabolic syndrome in humans.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this study insulin resistant (IR), young offspring of parents with type 2 diabetes (18-46&#xD;
      years) and healthy, lean elderly individuals (65-90 years) will undergo 1H/13C MRS&#xD;
      measurements of liver and muscle lipid and glycogen content before and after a high&#xD;
      carbohydrate meal challenge. Hepatic de novo lipogenesis will be determined as the&#xD;
      incorporation of deuterium, from deuterium labeled water (2H2O), into plasma triglycerides 5.&#xD;
      These metabolic studies will be performed in 3 sets: Study Part 1: Resting, Study Part 2:&#xD;
      After 1 bout of exercise and Study part 3: After 6 weeks of exercise training. Since&#xD;
      intra-abdominal obesity has been postulated to be at the core of the metabolic derangements&#xD;
      and directly responsible for the atherogenic dyslipidemia associated with the metabolic&#xD;
      syndrome, the investigators will also measure intra-abdominal fat content by magnetic&#xD;
      resonance imaging (MRI).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2017</start_date>
  <completion_date type="Actual">June 29, 2020</completion_date>
  <primary_completion_date type="Actual">June 29, 2020</primary_completion_date>
  <phase>N/A</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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>change in de novo lipogenesis</measure>
    <time_frame>Baseline</time_frame>
    <description>At the baseline assessment, de novo lipogenesis will be assessed by giving a high carbohydrate meal and heavy water to drink. Muscle glycogen and lipid contents pre- and post meal will be measured using 1H/13C MRS and de novo lipogenesis will be assessed from the heavy water incorporation into blood lipid in samples collected overnight.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change in de novo lipogenesis</measure>
    <time_frame>6 weeks</time_frame>
    <description>At the 6 weeks assessment, de novo lipogenesis will be assessed by giving a high carbohydrate meal and heavy water to drink. Muscle glycogen and lipid contents pre- and post meal will be measured using 1H/13C MRS and de novo lipogenesis will be assessed from the heavy water incorporation into blood lipid in samples collected overnight.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">41</enrollment>
  <condition>Insulin Resistance</condition>
  <arm_group>
    <arm_group_label>Exercise Training</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will engage in a single bout of elliptical exercise for 45 minutes (3X15 spaced by 5 minutes rest) at baseline. Subjects will be studied before and after this one bout to measure hepatic de novo lipogenesis. Participants will then take part in six weeks of exercise training on an elliptical trainer 3 times per week each time for 45 minutes. Hepatic de novo lipogenesis will be compared pre and post to examine wether improving muscle glucose uptake will decrease hepatic de novo lipogenesis as the glucose is taken up by muscle and not directed to the liver.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Exercise Training</intervention_name>
    <description>Six weeks of exercise</description>
    <arm_group_label>Exercise Training</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Body Mass Index &lt; 29 kg/m2&#xD;
&#xD;
          -  No regular exercise routine&#xD;
&#xD;
          -  Non-smokers&#xD;
&#xD;
          -  Absence of systemic and organ disease.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Hematocrit &lt; 35 vol%&#xD;
&#xD;
          -  History of claustrophobia&#xD;
&#xD;
          -  Ferromagnetic implants&#xD;
&#xD;
          -  Regular exercise regimen&#xD;
&#xD;
          -  Not weight stable&#xD;
&#xD;
          -  Any significant hematological, neurological, musculoskeletal or endocrine disease&#xD;
             (including diabetes mellitus)&#xD;
&#xD;
          -  Any significant cardiovascular condition, including confirmed CAD and prior&#xD;
             cardiovascular events&#xD;
&#xD;
          -  Taking coumadin as anticoagulant therapy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kitt Petersen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yale University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>YCCI/YNNH Hospital Research Unit</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06520</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Rabol R, Petersen KF, Dufour S, Flannery C, Shulman GI. Reversal of muscle insulin resistance with exercise reduces postprandial hepatic de novo lipogenesis in insulin resistant individuals. Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13705-9. doi: 10.1073/pnas.1110105108. Epub 2011 Aug 1.</citation>
    <PMID>21808028</PMID>
  </results_reference>
  <results_reference>
    <citation>Flannery C, Dufour S, Rabol R, Shulman GI, Petersen KF. Skeletal muscle insulin resistance promotes increased hepatic de novo lipogenesis, hyperlipidemia, and hepatic steatosis in the elderly. Diabetes. 2012 Nov;61(11):2711-7. doi: 10.2337/db12-0206. Epub 2012 Jul 24.</citation>
    <PMID>22829450</PMID>
  </results_reference>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>June 25, 2014</study_first_submitted>
  <study_first_submitted_qc>July 17, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 21, 2014</study_first_posted>
  <last_update_submitted>April 29, 2022</last_update_submitted>
  <last_update_submitted_qc>April 29, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 5, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Insulin resistance</keyword>
  <keyword>Exercise</keyword>
  <keyword>de novo lipogenesis</keyword>
  <keyword>NAFLD</keyword>
  <keyword>Magnetic Resonance Spectroscopy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin Resistance</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/NCT02196051
org study id: 0710003207
secondary id: R56AG023686
nct id: NCT02196051
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to examine the pathophysiology of insulin resistance and the
      relation to the metabolic syndrome in humans.
In this study insulin resistant (IR), young offspring of parents with type 2 diabetes (18-46
      years) and healthy, lean elderly individuals (65-90 years) will undergo 1H/13C MRS
      measurements of liver and muscle lipid and glycogen content before and after a high
      carbohydrate meal challenge. Hepatic de novo lipogenesis will be determined as the
      incorporation of deuterium, from deuterium labeled water (2H2O), into plasma triglycerides 5.
      These metabolic studies will be performed in 3 sets: Study Part 1: Resting, Study Part 2:
      After 1 bout of exercise and Study part 3: After 6 weeks of exercise training. Since
      intra-abdominal obesity has been postulated to be at the core of the metabolic derangements
      and directly responsible for the atherogenic dyslipidemia associated with the metabolic
      syndrome, the investigators will also measure intra-abdominal fat content by magnetic
      resonance imaging (MRI).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: change in de novo lipogenesis
time frame: Baseline
description: At the baseline assessment, de novo lipogenesis will be assessed by giving a high carbohydrate meal and heavy water to drink. Muscle glycogen and lipid contents pre- and post meal will be measured using 1H/13C MRS and de novo lipogenesis will be assessed from the heavy water incorporation into blood lipid in samples collected overnight.
measure: change in de novo lipogenesis
time frame: 6 weeks
description: At the 6 weeks assessment, de novo lipogenesis will be assessed by giving a high carbohydrate meal and heavy water to drink. Muscle glycogen and lipid contents pre- and post meal will be measured using 1H/13C MRS and de novo lipogenesis will be assessed from the heavy water incorporation into blood lipid in samples collected overnight.
arm group label: Exercise Training
arm group type: Experimental
description: Participants will engage in a single bout of elliptical exercise for 45 minutes (3X15 spaced by 5 minutes rest) at baseline. Subjects will be studied before and after this one bout to measure hepatic de novo lipogenesis. Participants will then take part in six weeks of exercise training on an elliptical trainer 3 times per week each time for 45 minutes. Hepatic de novo lipogenesis will be compared pre and post to examine wether improving muscle glucose uptake will decrease hepatic de novo lipogenesis as the glucose is taken up by muscle and not directed to the liver.
intervention type: Other
intervention name: Exercise Training
description: Six weeks of exercise
arm group label: Exercise Training
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Kitt Petersen, MD
role: Principal Investigator
affiliation: Yale University
facility: 
country: United States
citation: Rabol R, Petersen KF, Dufour S, Flannery C, Shulman GI. Reversal of muscle insulin resistance with exercise reduces postprandial hepatic de novo lipogenesis in insulin resistant individuals. Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13705-9. doi: 10.1073/pnas.1110105108. Epub 2011 Aug 1.
PMID: 21808028
citation: Flannery C, Dufour S, Rabol R, Shulman GI, Petersen KF. Skeletal muscle insulin resistance promotes increased hepatic de novo lipogenesis, hyperlipidemia, and hepatic steatosis in the elderly. Diabetes. 2012 Nov;61(11):2711-7. doi: 10.2337/db12-0206. Epub 2012 Jul 24.
PMID: 22829450
responsible party type: Sponsor
mesh term: Insulin Resistance
sharing ipd: No