<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/NCT04461015</url>
  </required_header>
  <id_info>
    <org_study_id>20-001570</org_study_id>
    <nct_id>NCT04461015</nct_id>
  </id_info>
  <brief_title>The Effect of the Interaction of Glucagon and Insulin on Endogenous Glucose Production in Humans</brief_title>
  <official_title>The Effect of the Interaction of Glucagon and Insulin on Endogenous Glucose Production in Humans</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Adrian Vella</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mayo Clinic</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this research is to help understand the relative importance of changes in&#xD;
      insulin secretion (which lowers glucose) and changes in glucagon (which raises glucose) to&#xD;
      regulate metabolism and the body's ability to make glucose.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study A (Insulin 0.4mU/Kg/min): Subjects will be admitted to the CRTU at approximately 1700&#xD;
      on the day prior to study. They will then consume a standard 10kcal/kg meal (55%&#xD;
      carbohydrate, 30% fat, 15% protein, caffeine free) and fast overnight. Blood will then be&#xD;
      sampled for baseline enrichment and 2H20 (1.67g/kg of body water) will be given in 3 divided&#xD;
      doses at 2200, 2400 and 0200. The following morning (approximately 0530), a forearm vein will&#xD;
      be cannulated to allow infusions to be performed. In addition, a cannula will be inserted&#xD;
      retrogradely into a vein of the contra-lateral dorsum of the hand. This will be placed in a&#xD;
      heated Plexiglas box maintained at around 120oF to allow sampling of arterialized venous&#xD;
      blood. At approximately 0600 (-180 min), a primed, (10microCi prime, 0.1microCi/min&#xD;
      continuous) infusion containing trace amounts of glucose labeled with [3-3H] glucose will be&#xD;
      started and continued till 0900 (0 min).&#xD;
&#xD;
      At 0900 (0 min), the infusion will be varied so as to mimic the anticipated pattern of fall&#xD;
      of EGP. In addition, glucose also labeled with [3-3H] glucose will be infused so as to&#xD;
      maintain glucose concentrations at ~ 95mg/dL. Peripheral venous glucose concentrations will&#xD;
      be measured every 10 minutes to allow the infusion rate of glucose to be adjusted as&#xD;
      necessary.&#xD;
&#xD;
      Simultaneously, an infusion of somatostatin (60ng/kg/min) will be started at time 0 to&#xD;
      inhibit endogenous islet secretion and therefore ensure identical portal insulin&#xD;
      concentrations on the two study days. Insulin will be infused at a constant rate known to&#xD;
      produce ~ 50% suppression of EGP (0.4mU/Kg/min).&#xD;
&#xD;
      From 0900 (0 min) to 1030 (90 min) no glucagon will be infused. Subsequently, a glucagon&#xD;
      infusion will commence (91 - 180 min) at 0.35 ng/Kg/min and then increase to 0.70 ng/Kg/min&#xD;
      (181- 270 min), a rate which will be maintained till the end of the study (1330).&#xD;
&#xD;
      Study B (0.8mU/Kg/min): Approximately 1-2 weeks after the first study visit, subjects will be&#xD;
      asked to return to the CRTU. This study visit will be similar to Study A. However, insulin&#xD;
      will be infused at 0.8mU/Kg/min 0 to 270 minutes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 14, 2020</start_date>
  <completion_date type="Actual">January 6, 2022</completion_date>
  <primary_completion_date type="Actual">July 30, 2021</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Endogenous Glucose Production (EGP)</measure>
    <time_frame>It will be quantified at 90, 180 and 270 minutes for the study with 0.4mU insulin infusion and compared to values obtained for the study with 0.8mU insulin infusion at the same timepoints</time_frame>
    <description>is calculated by tracer-based measurement and expressed per kg lean body mass</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>0.4mU Insulin</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>During the euglycemic clamp insulin will be infused at 0.4mU/Kg/Min</description>
  </arm_group>
  <arm_group>
    <arm_group_label>0.8mU Insulin</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>During the euglycemic clamp insulin will be infused at 0.8mU/Kg/Min</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>0.4mU Insulin followed by withdrawal period followed by 0.8mU study</intervention_name>
    <description>Clamp study with insulin infused at 0.4 mU/Kg/min, followed by a 2 week withdrawal period followed by a clamp study with insulin infused at 0.8 mU/Kg/min</description>
    <arm_group_label>0.4mU Insulin</arm_group_label>
    <arm_group_label>0.8mU Insulin</arm_group_label>
    <other_name>0.4 then 0.8</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>0.8mU Insulin followed by withdrawal period followed by 0.4mU study</intervention_name>
    <description>Clamp study with insulin infused at 0.8 mU/Kg/min, followed by a 2 week withdrawal period followed by a clamp study with insulin infused at 0.4 mU/Kg/min</description>
    <arm_group_label>0.4mU Insulin</arm_group_label>
    <arm_group_label>0.8mU Insulin</arm_group_label>
    <other_name>0.8 then 0.4</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  We will recruit 15 otherwise healthy subjects using intramural and local extramural&#xD;
             advertising after approval from the Mayo Clinic Institutional Review Board.&#xD;
             Individuals who express interest in participating will be invited for a screening&#xD;
             visit. Individuals with a BMI &lt; 19 or &gt; 28 kg/m2 will be excluded from the study to&#xD;
             avoid potential confounding effects that may result from extreme leanness or from&#xD;
             obesity. Subjects will have no known systemic illness, taking any medication that&#xD;
             could affect glucose metabolism and no history of upper gastrointestinal surgery.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects &lt; 18 years of age or &gt; 40 years of age will not be studied to minimize the&#xD;
             potential confounding effects of age on glucagon and insulin action. The subjects will&#xD;
             not be taking medications that affect glucose metabolism (to be determined by PI) and&#xD;
             have no history of chronic illness or upper gastrointestinal surgery. We are seeking&#xD;
             to recruit subjects who do not have diabetes (fasting glucose &lt;100mg/dL).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Adrian Vella</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic in Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </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>May 2022</verification_date>
  <study_first_submitted>June 30, 2020</study_first_submitted>
  <study_first_submitted_qc>July 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 8, 2020</study_first_posted>
  <results_first_submitted>April 5, 2022</results_first_submitted>
  <results_first_submitted_qc>May 25, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">June 21, 2022</results_first_posted>
  <last_update_submitted>May 25, 2022</last_update_submitted>
  <last_update_submitted_qc>May 25, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Adrian Vella</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin</mesh_term>
    <mesh_term>Insulin, Globin Zinc</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 13, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/15/NCT04461015/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>The study is a cross-over study - subjects participated in both arms</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>0.4 Then 0.8</title>
          <description>During the first euglycemic clamp insulin will be infused at 0.4mU/Kg/Min&#xD;
Subjects will undergo a 15 day 'withdrawal period'&#xD;
During the second euglycemic clamp insulin will be infused at 0.8mU/Kg/Min</description>
        </group>
        <group group_id="P2">
          <title>0.8 Then 0.4</title>
          <description>During the euglycemic clamp insulin will be infused at 0.8mU/Kg/Min&#xD;
Subjects will undergo a 15 day 'withdrawal period'&#xD;
During the second euglycemic clamp insulin will be infused at 0.4mU/Kg/Min</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>IV access lost during the study</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>0.4 Then 0.8</title>
          <description>Subjects will undergo the 0.4 clamp first during which insulin is infused at 0.4mU/Kg/Min&#xD;
following a suitable washout period,&#xD;
Subjects will undergo the 0.8 clamp second during which insulin is infused at 0.8mU/Kg/Min</description>
        </group>
        <group group_id="B2">
          <title>0.8 Then 0.4</title>
          <description>Subjects will undergo the 0.8 clamp first during which insulin is infused at 0.8mU/Kg/Min&#xD;
following a suitable washout period,&#xD;
Subjects will undergo the 0.4 clamp second during which insulin is infused at 0.4mU/Kg/Min</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="5"/>
            <count group_id="B2" value="7"/>
            <count group_id="B3" value="12"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <population>Analysis in people completing both arms</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="5"/>
                    <count group_id="B2" value="5"/>
                    <count group_id="B3" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <population>Analysis in people completing both arms</population>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="5"/>
                    <count group_id="B2" value="5"/>
                    <count group_id="B3" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="34" spread="13"/>
                    <measurement group_id="B2" value="37" spread="10"/>
                    <measurement group_id="B3" value="35" spread="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="5"/>
                    <count group_id="B2" value="7"/>
                    <count group_id="B3" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="5"/>
                    <count group_id="B2" value="7"/>
                    <count group_id="B3" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Endogenous Glucose Production (EGP)</title>
        <description>is calculated by tracer-based measurement and expressed per kg lean body mass</description>
        <time_frame>It will be quantified at 90, 180 and 270 minutes for the study with 0.4mU insulin infusion and compared to values obtained for the study with 0.8mU insulin infusion at the same timepoints</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.4mU Insulin</title>
            <description>During the euglycemic clamp insulin will be infused at 0.4mU/Kg/Min&#xD;
0.4mU Insulin: Insulin infused at 0.4 mU/Kg/min</description>
          </group>
          <group group_id="O2">
            <title>0.8mU Insulin</title>
            <description>During the euglycemic clamp insulin will be infused at 0.8mU/Kg/Min&#xD;
0.8mU Insulin: Insulin infused at 0.8 mU/Kg/min</description>
          </group>
        </group_list>
        <measure>
          <title>Endogenous Glucose Production (EGP)</title>
          <description>is calculated by tracer-based measurement and expressed per kg lean body mass</description>
          <units>umol/kg/min</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>At 90 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.99" spread="0.53"/>
                    <measurement group_id="O2" value="5.02" spread="0.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At 180 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.82" spread="0.82"/>
                    <measurement group_id="O2" value="5.52" spread="0.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At 270 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.48" spread="1.07"/>
                    <measurement group_id="O2" value="5.38" spread="1.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>3 months</time_frame>
      <desc>These young healthy participants were in the study for duration of time between screening, and the end of the last experiment. Each of the experiments was 270 minutes long but subjects were admitted the night before and monitored in house till the end of the experiment. After the first experiment there was a 15 day waiting period and then another experiment (with admission the night before).</desc>
      <group_list>
        <group group_id="E1">
          <title>0.4 Events</title>
          <description>Events occurring during the 0.4 euglycemic clamp when insulin was infused at 0.4mU/Kg/Min</description>
        </group>
        <group group_id="E2">
          <title>0.8 Events</title>
          <description>Events occurring during the 0.8 euglycemic clamp when insulin was infused at 0.8mU/Kg/Min</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Phlebitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The main caveat is that during the experiment insulin is kept constant - i.e. not quite like what happens in the postprandial situation</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Adrian Vella</name_or_title>
      <organization>Mayo Clinic</organization>
      <phone>507-255-6515</phone>
      <email>vella.adrian@mayo.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT04461015
org study id: 20-001570
nct id: NCT04461015
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this research is to help understand the relative importance of changes in
      insulin secretion (which lowers glucose) and changes in glucagon (which raises glucose) to
      regulate metabolism and the body's ability to make glucose.
Study A (Insulin 0.4mU/Kg/min): Subjects will be admitted to the CRTU at approximately 1700
      on the day prior to study. They will then consume a standard 10kcal/kg meal (55%
      carbohydrate, 30% fat, 15% protein, caffeine free) and fast overnight. Blood will then be
      sampled for baseline enrichment and 2H20 (1.67g/kg of body water) will be given in 3 divided
      doses at 2200, 2400 and 0200. The following morning (approximately 0530), a forearm vein will
      be cannulated to allow infusions to be performed. In addition, a cannula will be inserted
      retrogradely into a vein of the contra-lateral dorsum of the hand. This will be placed in a
      heated Plexiglas box maintained at around 120oF to allow sampling of arterialized venous
      blood. At approximately 0600 (-180 min), a primed, (10microCi prime, 0.1microCi/min
      continuous) infusion containing trace amounts of glucose labeled with [3-3H] glucose will be
      started and continued till 0900 (0 min).

      At 0900 (0 min), the infusion will be varied so as to mimic the anticipated pattern of fall
      of EGP. In addition, glucose also labeled with [3-3H] glucose will be infused so as to
      maintain glucose concentrations at ~ 95mg/dL. Peripheral venous glucose concentrations will
      be measured every 10 minutes to allow the infusion rate of glucose to be adjusted as
      necessary.

      Simultaneously, an infusion of somatostatin (60ng/kg/min) will be started at time 0 to
      inhibit endogenous islet secretion and therefore ensure identical portal insulin
      concentrations on the two study days. Insulin will be infused at a constant rate known to
      produce ~ 50% suppression of EGP (0.4mU/Kg/min).

      From 0900 (0 min) to 1030 (90 min) no glucagon will be infused. Subsequently, a glucagon
      infusion will commence (91 - 180 min) at 0.35 ng/Kg/min and then increase to 0.70 ng/Kg/min
      (181- 270 min), a rate which will be maintained till the end of the study (1330).

      Study B (0.8mU/Kg/min): Approximately 1-2 weeks after the first study visit, subjects will be
      asked to return to the CRTU. This study visit will be similar to Study A. However, insulin
      will be infused at 0.8mU/Kg/min 0 to 270 minutes.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Endogenous Glucose Production (EGP)
time frame: It will be quantified at 90, 180 and 270 minutes for the study with 0.4mU insulin infusion and compared to values obtained for the study with 0.8mU insulin infusion at the same timepoints
description: is calculated by tracer-based measurement and expressed per kg lean body mass
arm group label: 0.4mU Insulin
arm group type: Other
description: During the euglycemic clamp insulin will be infused at 0.4mU/Kg/Min
arm group label: 0.8mU Insulin
arm group type: Other
description: During the euglycemic clamp insulin will be infused at 0.8mU/Kg/Min
intervention type: Drug
intervention name: 0.4mU Insulin followed by withdrawal period followed by 0.8mU study
description: Clamp study with insulin infused at 0.4 mU/Kg/min, followed by a 2 week withdrawal period followed by a clamp study with insulin infused at 0.8 mU/Kg/min
arm group label: 0.4mU Insulin
arm group label: 0.8mU Insulin
other name: 0.4 then 0.8
intervention type: Drug
intervention name: 0.8mU Insulin followed by withdrawal period followed by 0.4mU study
description: Clamp study with insulin infused at 0.8 mU/Kg/min, followed by a 2 week withdrawal period followed by a clamp study with insulin infused at 0.4 mU/Kg/min
arm group label: 0.4mU Insulin
arm group label: 0.8mU Insulin
other name: 0.8 then 0.4
criteria: 
gender: All
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Adrian Vella
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
country: United States
url: https://www.mayo.edu/research/clinical-trials
description: Mayo Clinic Clinical Trials
responsible party type: Sponsor-Investigator
investigator affiliation: Mayo Clinic
investigator full name: Adrian Vella
investigator title: Principal Investigator
mesh term: Insulin
mesh term: Insulin, Globin Zinc
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The main caveat is that during the experiment insulin is kept constant - i.e. not quite like what happens in the postprandial situation
point of contact: 