<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/NCT03818178</url>
  </required_header>
  <id_info>
    <org_study_id>18-002520</org_study_id>
    <secondary_id>5R01DK045343-27</secondary_id>
    <nct_id>NCT03818178</nct_id>
  </id_info>
  <brief_title>Intramyocellular Fatty Acid Trafficking in Insulin Resistance States - Effects of Intestinal Delivery of Lipids</brief_title>
  <official_title>Intramyocellular Fatty Acid Trafficking in Insulin Resistance States - Effects of Intestinal Delivery of Lipids</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Mayo Clinic</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>
      Muscle insulin resistance is a hallmark of upper body obesity (UBO) and Type 2 diabetes&#xD;
      (T2DM). It is unknown whether muscle free fatty acid (FFA) availability or intramyocellular&#xD;
      fatty acid trafficking is responsible for muscle insulin resistance, although it has been&#xD;
      shown that raising FFA with Intralipid can cause muscle insulin resistance within 4 hours.&#xD;
      The investigators do not understand to what extent the incorporation of FFA into ceramides or&#xD;
      diacylglycerols (DG) affect insulin signaling and muscle glucose uptake. The investigators&#xD;
      propose to alter the profile and concentrations of FFA of healthy, non-obese adults using an&#xD;
      overnight, intra-duodenal palm oil infusion vs. an overnight intra-duodenal Intralipid&#xD;
      infusion (both compared to saline control). The investigators will compare the muscle FFA&#xD;
      storage into intramyocellular triglyceride, intramyocellular fatty acid trafficking,&#xD;
      activation of the insulin signaling pathway and glucose disposal rates, providing the first&#xD;
      measure of how different FFA profiles alter muscle FFA trafficking and insulin action at the&#xD;
      whole body and cellular/molecular levels. By identifying which steps in the insulin signaling&#xD;
      pathway are most affected, the investigators will determine the site-specific effect of&#xD;
      ceramides and/or DG on different degrees of insulin resistance.&#xD;
&#xD;
      Hypothesis 1: Palm oil infusion will result in abnormal FFA trafficking into&#xD;
      intra-myocellular ceramides and abnormal insulin signaling.&#xD;
&#xD;
      Hypothesis 2: Intralipid infusion will result in abnormal FFA trafficking into&#xD;
      intra-myocellular saturated DG and abnormal insulin signaling.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 1, 2018</start_date>
  <completion_date type="Anticipated">January 2024</completion_date>
  <primary_completion_date type="Anticipated">January 2024</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in fatty acid enrichment of intramyocellular signaling molecules before and after a euglycemic, hyperinsulinemic clamp</measure>
    <time_frame>18 hours</time_frame>
    <description>The study involves the use of a hyperinsulinemic, euglycemic clamp to compare fatty acid enrichments in intramyocellular signaling molecules. The first half of the study will be the &quot;pre-clamp&quot; stage. During this stage, volunteers will receive an intravenous infusion of C13-labelled palmitate as a tracer in order for enrichment calculations to be performed pre-clamp. One muscle biopsy will be obtained to measure fatty acid enrichment within intramyocellular ceramides, diacylglycerols, long-chain acylcarnitines, and intramyocellular triglycerides. The insulin clamp will then commence, and volunteers will simultaneously receive an intravenous infusion of a second tracer, D-9 palmitate. This tracer will allow us to calculate enrichments during the insulin clamp stage of the study. A second muscle biopsy will be performed at the end of the insulin clamp, and similar enrichment calculations will be performed.</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Insulin Resistance</condition>
  <arm_group>
    <arm_group_label>Intralipid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Palm Oil</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Saline</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Intralipid</intervention_name>
    <description>Half of the participants will receive either naso-duodenal infusion of intralipid or palm oil each participant will serve as their own saline control on the second study day.</description>
    <arm_group_label>Intralipid</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Palm Oil Emulsion</intervention_name>
    <description>Half of the participants will receive either naso-duodenal infusion of intralipid or palm oil each participant will serve as their own saline control on the second study day.</description>
    <arm_group_label>Palm Oil</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Saline</intervention_name>
    <description>All participants will serve as their own controls with a saline infusion study day.</description>
    <arm_group_label>Saline</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women and Men (Women premenopausal)&#xD;
&#xD;
          -  BMI 18-27&#xD;
&#xD;
          -  Weight stable&#xD;
&#xD;
          -  Not pregnant/nursing&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Ischemic heart disease&#xD;
&#xD;
          -  Atherosclerotic valvular disease&#xD;
&#xD;
          -  Smokers (&gt; 20 cigarettes per week)&#xD;
&#xD;
          -  Bilateral oophorectomy&#xD;
&#xD;
          -  Concomitant use of medications that can alter serum lipid profile (high dose fish oil,&#xD;
             statins, niacin, fibrates, thiazolinediones, beta-blockers, atypical antipsychotics)&#xD;
&#xD;
          -  Lidocaine allergy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael D Jensen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Pamela Reich</last_name>
    <phone>507-255-6062</phone>
    <email>Reich.Pamela@mayo.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Pamela A Reich, SC</last_name>
      <phone>507-255-6062</phone>
      <email>reich.pamela@mayo.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.mayo.edu/research/clinical-trials</url>
    <description>Mayo Clinic Clinical Trials</description>
  </link>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>January 20, 2019</study_first_submitted>
  <study_first_submitted_qc>January 25, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <last_update_submitted>February 22, 2023</last_update_submitted>
  <last_update_submitted_qc>February 22, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Michael D. Jensen</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin Resistance</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Soybean oil, phospholipid emulsion</mesh_term>
  </intervention_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/NCT03818178
org study id: 18-002520
secondary id: 5R01DK045343-27
nct id: NCT03818178
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Muscle insulin resistance is a hallmark of upper body obesity (UBO) and Type 2 diabetes
      (T2DM). It is unknown whether muscle free fatty acid (FFA) availability or intramyocellular
      fatty acid trafficking is responsible for muscle insulin resistance, although it has been
      shown that raising FFA with Intralipid can cause muscle insulin resistance within 4 hours.
      The investigators do not understand to what extent the incorporation of FFA into ceramides or
      diacylglycerols (DG) affect insulin signaling and muscle glucose uptake. The investigators
      propose to alter the profile and concentrations of FFA of healthy, non-obese adults using an
      overnight, intra-duodenal palm oil infusion vs. an overnight intra-duodenal Intralipid
      infusion (both compared to saline control). The investigators will compare the muscle FFA
      storage into intramyocellular triglyceride, intramyocellular fatty acid trafficking,
      activation of the insulin signaling pathway and glucose disposal rates, providing the first
      measure of how different FFA profiles alter muscle FFA trafficking and insulin action at the
      whole body and cellular/molecular levels. By identifying which steps in the insulin signaling
      pathway are most affected, the investigators will determine the site-specific effect of
      ceramides and/or DG on different degrees of insulin resistance.

      Hypothesis 1: Palm oil infusion will result in abnormal FFA trafficking into
      intra-myocellular ceramides and abnormal insulin signaling.

      Hypothesis 2: Intralipid infusion will result in abnormal FFA trafficking into
      intra-myocellular saturated DG and abnormal insulin signaling.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Change in fatty acid enrichment of intramyocellular signaling molecules before and after a euglycemic, hyperinsulinemic clamp
time frame: 18 hours
description: The study involves the use of a hyperinsulinemic, euglycemic clamp to compare fatty acid enrichments in intramyocellular signaling molecules. The first half of the study will be the "pre-clamp" stage. During this stage, volunteers will receive an intravenous infusion of C13-labelled palmitate as a tracer in order for enrichment calculations to be performed pre-clamp. One muscle biopsy will be obtained to measure fatty acid enrichment within intramyocellular ceramides, diacylglycerols, long-chain acylcarnitines, and intramyocellular triglycerides. The insulin clamp will then commence, and volunteers will simultaneously receive an intravenous infusion of a second tracer, D-9 palmitate. This tracer will allow us to calculate enrichments during the insulin clamp stage of the study. A second muscle biopsy will be performed at the end of the insulin clamp, and similar enrichment calculations will be performed.
arm group label: Intralipid
arm group type: Experimental
arm group label: Palm Oil
arm group type: Experimental
arm group label: Saline
arm group type: Placebo Comparator
intervention type: Dietary Supplement
intervention name: Intralipid
description: Half of the participants will receive either naso-duodenal infusion of intralipid or palm oil each participant will serve as their own saline control on the second study day.
arm group label: Intralipid
intervention type: Dietary Supplement
intervention name: Palm Oil Emulsion
description: Half of the participants will receive either naso-duodenal infusion of intralipid or palm oil each participant will serve as their own saline control on the second study day.
arm group label: Palm Oil
intervention type: Other
intervention name: Saline
description: All participants will serve as their own controls with a saline infusion study day.
arm group label: Saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Michael D Jensen, MD
role: Principal Investigator
affiliation: Mayo Clinic
last name: Pamela Reich
phone: 507-255-6062
email: Reich.Pamela@mayo.edu
facility: 
status: Recruiting
contact: 
country: United States
url: https://www.mayo.edu/research/clinical-trials
description: Mayo Clinic Clinical Trials
responsible party type: Principal Investigator
investigator affiliation: Mayo Clinic
investigator full name: Michael D. Jensen
investigator title: Principal Investigator
mesh term: Insulin Resistance
mesh term: Soybean oil, phospholipid emulsion