<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/NCT04459338</url>
  </required_header>
  <id_info>
    <org_study_id>20-003995</org_study_id>
    <secondary_id>5R01DK126206-03</secondary_id>
    <nct_id>NCT04459338</nct_id>
  </id_info>
  <brief_title>A Dose-response Study Examining the Contribution of GLP-1 Receptor Signaling to Glucagon-stimulated Insulin Secretion</brief_title>
  <official_title>A Dose-response Study Examining the Contribution of GLP-1 Receptor Signaling to Glucagon-stimulated Insulin Secretion</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Adrian Vella</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>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The GLP-1 receptor (GLP1R) gene is found on the beta cells of the pancreas. Its role is in&#xD;
      the control of blood sugar level by enhancing insulin secretion from the pancreas after&#xD;
      eating a meal. The purpose of this research study is to evaluate the role of GLP1R in the&#xD;
      response to elevated glucagon concentrations.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Glucagon within the islet can signal the β-cell through GLP1R, and acts as an insulin&#xD;
      secretagogue. This signaling is blocked by exendin-9,39. The relative importance of glucagon&#xD;
      signaling through its cognate receptor or through GLP1R is unknown. Despite the lower&#xD;
      affinity of GLP1R for glucagon, intra-islet concentrations of glucagon are sufficiently high&#xD;
      to stimulate GLP1R. The other situation where this may occur is in response to pharmacologic&#xD;
      doses of glucagon as used for β-cell function testing or raising peripheral glucagon&#xD;
      concentrations above fasting values. The experiments proposed will characterize the role of&#xD;
      GLP1R in glucagon's actions on the β-cell and the potential therapeutic role of dual (GLP-1R&#xD;
      and glucagon receptor) agonists for the treatment of T2DM and obesity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 4, 2021</start_date>
  <completion_date type="Actual">June 14, 2022</completion_date>
  <primary_completion_date type="Actual">June 14, 2022</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>Insulin Secretion Rate During Exendin-9,39 Infusion vs. Insulin Secretion Rate During Saline Infusion</measure>
    <time_frame>Area under the curve was quantified at the end of the Saline Study and at the end of the Exendin-9,39 study</time_frame>
    <description>This is the area under the curve for insulin secretion over the duration of the hyperglycemic clamp (0 to 300 minutes during the study in the Clinical Research Unit).</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">11</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Saline, Then Exendin-9,39</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A week or two after screening, participants were admitted to the CRTU and Saline was infused during a hyperglycemic clamp during which escalating doses of glucagon were infused. After completion of this study participants underwent a washout period of 2 weeks after which they were readmitted to the CRTU and Exendin-9,39 was infused at 300pmol/kg/min was infused during a hyperglycemic clamp during which escalating doses of glucagon were infused.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Exendin-9,39, Then Saline</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A week or two after screening, participants were admitted to the CRTU and Exendin-9,39 was infused at 300pmol/kg/min during a hyperglycemic clamp during which escalating doses of glucagon were infused. After completion of this study participants underwent a washout period of 2 weeks after which they were readmitted to the CRTU and Saline was infused during a hyperglycemic clamp during which escalating doses of glucagon were infused.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Exendin-9,39</intervention_name>
    <description>Exendin-9,39 is a competitive antagonist of GLP-1 actions at the GLP-1 receptor</description>
    <arm_group_label>Exendin-9,39, Then Saline</arm_group_label>
    <arm_group_label>Saline, Then Exendin-9,39</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Saline</intervention_name>
    <description>Placebo comparator</description>
    <arm_group_label>Exendin-9,39, Then Saline</arm_group_label>
    <arm_group_label>Saline, Then Exendin-9,39</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  20 weight-stable, non-diabetic subjects&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age &lt; 25 or &gt; 65 years (to avoid studying subjects who could have latent type 1&#xD;
             diabetes, or the effects of age extremes in subjects with normal or impaired fasting&#xD;
             glucose).&#xD;
&#xD;
          -  HbA1c ≥5.9%&#xD;
&#xD;
          -  Use of glucose-lowering agents.&#xD;
&#xD;
          -  For female subjects: positive pregnancy test at the time of enrollment or study&#xD;
&#xD;
          -  History of prior upper abdominal surgery such as adjustable gastric banding,&#xD;
             pyloroplasty and vagotomy.&#xD;
&#xD;
          -  Active systemic illness or malignancy.&#xD;
&#xD;
          -  Symptomatic macrovascular or microvascular disease.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>25 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Adrian Vella, MD</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>June 2023</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 7, 2020</study_first_posted>
  <results_first_submitted>March 15, 2023</results_first_submitted>
  <results_first_submitted_qc>June 8, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">June 9, 2023</results_first_posted>
  <last_update_submitted>June 8, 2023</last_update_submitted>
  <last_update_submitted_qc>June 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 9, 2023</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>
  <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>March 26, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/38/NCT04459338/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Healthy volunteers responded to intramural advertising at the Mayo Clinic between March 2021 and September 2021</recruitment_details>
      <pre_assignment_details>None of the enrolled subjects were excluded and all were randomized</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Saline, Then Exendin-9,39</title>
          <description>Subjects are admitted to the Clinical research unit the night before the study and the following morning after an overnight fast, at time 0 glucose is infused to raise concentrations to 165mg/dL. At the same time a glucagon infusion commences at 0.4ng/kg/min. At 60 min the infusion increases to 0.6ng/kg/min, at 120 min to 0.8ng/kg/min, at 180 min 1.0 ng/kg/min, and at 240 min 1.2 ng/kg/min. The glucagon infusion ends at 300 min. Saline infusion is started at time 0 and continues for 300 minutes.&#xD;
There is then a washout period of 14 days minimum&#xD;
Subjects are admitted to the Clinical research unit the night before the 2nd study and the following morning after an overnight fast, at time 0 glucose is infused to raise concentrations to 165mg/dL. At the same time a glucagon infusion commences at 0.4ng/kg/min. At 60 min the infusion increases to 0.6ng/kg/min, at 120 min to 0.8ng/kg/min, at 180 min 1.0 ng/kg/min, and at 240 min 1.2 ng/kg/min. The glucagon infusion ends at 300 min. Exendin-9,39 infusion is started at time 0 and continues for 300 minutes.</description>
        </group>
        <group group_id="P2">
          <title>Exendin-9,39, Then Saline</title>
          <description>Subjects are admitted to the Clinical research unit the night before the study and the following morning after an overnight fast, at time 0 glucose is infused to raise concentrations to 165mg/dL. At the same time a glucagon infusion commences at 0.4ng/kg/min. At 60 min the infusion increases to 0.6ng/kg/min, at 120 min to 0.8ng/kg/min, at 180 min 1.0 ng/kg/min, and at 240 min 1.2 ng/kg/min. The glucagon infusion ends at 300 min. Exendin-9,39 infusion is started at time 0 and continues for 300 minutes.&#xD;
There is then a washout period of 14 days minimum&#xD;
Subjects are admitted to the Clinical research unit the night before the 2nd study and the following morning after an overnight fast, at time 0 glucose is infused to raise concentrations to 165mg/dL. At the same time a glucagon infusion commences at 0.4ng/kg/min. At 60 min the infusion increases to 0.6ng/kg/min, at 120 min to 0.8ng/kg/min, at 180 min 1.0 ng/kg/min, and at 240 min 1.2 ng/kg/min. The glucagon infusion ends at 300 min. Saline infusion is started at time 0 and continues for 300 minutes.</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="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Loss of IV during study</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Subjects without diabetes to enable evaluation of insulin secretory capacity</population>
      <group_list>
        <group group_id="B1">
          <title>All Participants</title>
          <description>All participants were randomized to receive all interventions</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="11"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</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="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <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="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26" spread="3"/>
                  </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="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" 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_list>
                </analyzed>
              </analyzed_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="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Insulin Secretion Rate During Exendin-9,39 Infusion vs. Insulin Secretion Rate During Saline Infusion</title>
        <description>This is the area under the curve for insulin secretion over the duration of the hyperglycemic clamp (0 to 300 minutes during the study in the Clinical Research Unit).</description>
        <time_frame>Area under the curve was quantified at the end of the Saline Study and at the end of the Exendin-9,39 study</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Insulin Secretion During the Saline Study</title>
            <description>Subjects are admitted to the Clinical research unit the night before the study and the following morning after an overnight fast, at time 0 glucose is infused to raise concentrations to 165mg/dL. At the same time a glucagon infusion commences at 0.4ng/kg/min. At 60 min the infusion increases to 0.6ng/kg/min, at 120 min to 0.8ng/kg/min, at 180 min 1.0 ng/kg/min, and at 240 min 1.2 ng/kg/min. The glucagon infusion ends at 300 min. Saline infusion is started at time 0 and continues for 300 minutes.</description>
          </group>
          <group group_id="O2">
            <title>Insulin Secretion During the Exendin-9,39 Study</title>
            <description>Subjects are admitted to the Clinical research unit the night before the study and the following morning after an overnight fast, at time 0 glucose is infused to raise concentrations to 165mg/dL. At the same time a glucagon infusion commences at 0.4ng/kg/min. At 60 min the infusion increases to 0.6ng/kg/min, at 120 min to 0.8ng/kg/min, at 180 min 1.0 ng/kg/min, and at 240 min 1.2 ng/kg/min. The glucagon infusion ends at 300 min. Exendin-9,39 infusion is started at time 0 and continues for 300 minutes.</description>
          </group>
        </group_list>
        <measure>
          <title>Insulin Secretion Rate During Exendin-9,39 Infusion vs. Insulin Secretion Rate During Saline Infusion</title>
          <description>This is the area under the curve for insulin secretion over the duration of the hyperglycemic clamp (0 to 300 minutes during the study in the Clinical Research Unit).</description>
          <units>nmol/min per 300 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="11"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="191" spread="23"/>
                    <measurement group_id="O2" value="171" spread="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>All continuous data are summarized as means ± SEM. Area Under the Curve (AUC) was calculated using the trapezoidal rule. A paired, two-way Student t-test (parametric) or a Wilcoxon matched-pairs signed rank test (non-parametric) was used to examine differences between study days. A p-value &lt;0.05 was considered statistically significant.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.02</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Time between screening and completion of the study = 6 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Saline</title>
          <description>Subjects are admitted to the Clinical research unit the night before the study and the following morning after an overnight fast, at time 0 glucose is infused to raise concentrations to 165mg/dL. At the same time a glucagon infusion commences at 0.4ng/kg/min. At 60 min the infusion increases to 0.6ng/kg/min, at 120 min to 0.8ng/kg/min, at 180 min 1.0 ng/kg/min, and at 240 min 1.2 ng/kg/min. The glucagon infusion ends at 300 min. Saline infusion is started at time 0 and continues for 300 minutes.</description>
        </group>
        <group group_id="E2">
          <title>Exendin-9,39</title>
          <description>Subjects are admitted to the Clinical research unit the night before the study and the following morning after an overnight fast, at time 0 glucose is infused to raise concentrations to 165mg/dL. At the same time a glucagon infusion commences at 0.4ng/kg/min. At 60 min the infusion increases to 0.6ng/kg/min, at 120 min to 0.8ng/kg/min, at 180 min 1.0 ng/kg/min, and at 240 min 1.2 ng/kg/min. The glucagon infusion ends at 300 min. Exendin-9,39 infusion is started at time 0 and continues for 300 minutes.</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="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-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="2" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <description>Nausea with glucagon infusion</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Infusion line lost</sub_title>
                <description>Phlebitis</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </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>
    <point_of_contact>
      <name_or_title>Adrian Vella</name_or_title>
      <organization>Mayo Clinic</organization>
      <phone>507-284-3754</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/NCT04459338
org study id: 20-003995
secondary id: 5R01DK126206-03
nct id: NCT04459338
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The GLP-1 receptor (GLP1R) gene is found on the beta cells of the pancreas. Its role is in
      the control of blood sugar level by enhancing insulin secretion from the pancreas after
      eating a meal. The purpose of this research study is to evaluate the role of GLP1R in the
      response to elevated glucagon concentrations.
Glucagon within the islet can signal the β-cell through GLP1R, and acts as an insulin
      secretagogue. This signaling is blocked by exendin-9,39. The relative importance of glucagon
      signaling through its cognate receptor or through GLP1R is unknown. Despite the lower
      affinity of GLP1R for glucagon, intra-islet concentrations of glucagon are sufficiently high
      to stimulate GLP1R. The other situation where this may occur is in response to pharmacologic
      doses of glucagon as used for β-cell function testing or raising peripheral glucagon
      concentrations above fasting values. The experiments proposed will characterize the role of
      GLP1R in glucagon's actions on the β-cell and the potential therapeutic role of dual (GLP-1R
      and glucagon receptor) agonists for the treatment of T2DM and obesity.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Insulin Secretion Rate During Exendin-9,39 Infusion vs. Insulin Secretion Rate During Saline Infusion
time frame: Area under the curve was quantified at the end of the Saline Study and at the end of the Exendin-9,39 study
description: This is the area under the curve for insulin secretion over the duration of the hyperglycemic clamp (0 to 300 minutes during the study in the Clinical Research Unit).
arm group label: Saline, Then Exendin-9,39
arm group type: Experimental
description: A week or two after screening, participants were admitted to the CRTU and Saline was infused during a hyperglycemic clamp during which escalating doses of glucagon were infused. After completion of this study participants underwent a washout period of 2 weeks after which they were readmitted to the CRTU and Exendin-9,39 was infused at 300pmol/kg/min was infused during a hyperglycemic clamp during which escalating doses of glucagon were infused.
arm group label: Exendin-9,39, Then Saline
arm group type: Experimental
description: A week or two after screening, participants were admitted to the CRTU and Exendin-9,39 was infused at 300pmol/kg/min during a hyperglycemic clamp during which escalating doses of glucagon were infused. After completion of this study participants underwent a washout period of 2 weeks after which they were readmitted to the CRTU and Saline was infused during a hyperglycemic clamp during which escalating doses of glucagon were infused.
intervention type: Biological
intervention name: Exendin-9,39
description: Exendin-9,39 is a competitive antagonist of GLP-1 actions at the GLP-1 receptor
arm group label: Exendin-9,39, Then Saline
arm group label: Saline, Then Exendin-9,39
intervention type: Other
intervention name: Saline
description: Placebo comparator
arm group label: Exendin-9,39, Then Saline
arm group label: Saline, Then Exendin-9,39
criteria: 
gender: All
minimum age: 25 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Adrian Vella, MD
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
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 