<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/NCT01701973</url>
  </required_header>
  <id_info>
    <org_study_id>120078</org_study_id>
    <secondary_id>1K23HL119602</secondary_id>
    <nct_id>NCT01701973</nct_id>
  </id_info>
  <brief_title>Effect of DPP4 Inhibition on Growth Hormone Secretion</brief_title>
  <official_title>The Effect of Dipeptidyl Peptidase IV Inhibition on Growth Hormone-Mediated Vasodilation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderbilt University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Vanderbilt University Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study tests the following hypotheses:&#xD;
&#xD;
      Aim 1: Test the hypothesis that acute dipeptidyl peptidase 4 (DPP4) inhibition with the&#xD;
      currently available anti-diabetic drug, sitagliptin, will increase stimulated growth hormone&#xD;
      (GH) secretion in healthy lean adults by decreasing the degradation of growth hormone&#xD;
      releasing hormone (GHRH).&#xD;
&#xD;
      Aim 2: Test the hypothesis that decreased degradation of GHRH during acute DPP4 inhibition&#xD;
      will result in an increase in endothelium-dependent vasodilation mediated by GH and&#xD;
      independent from GLP1 (glucagon like peptide-1) in healthy lean adults.&#xD;
&#xD;
      This study promises to provide novel data regarding how this increasingly used class of&#xD;
      anti-diabetic drugs affects the pituitary GH axis and could affect blood vessel relaxation.&#xD;
      Growth hormone levels are low in the setting of obesity and pre-diabetes. A further study may&#xD;
      evaluate the effect of chronic DPP4 inhibitor therapy in a population of patients with&#xD;
      obesity and pre-diabetes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Growth hormone secretion is low in patients with obesity, insulin resistance, and&#xD;
      hyperlipidemia. GH therapy in these populations and others has been limited by side effects&#xD;
      which include hyperglycemia. Another strategy to increase GH secretion is to enhance&#xD;
      pulsatile GH secretion by growth hormone releasing hormone. Growth hormone releasing hormone&#xD;
      (GHRH) has a half life of 5 minutes due to its rapid inactivation by DPP4. An alternative&#xD;
      strategy to increase endogenous GH secretion is by inhibiting degradation of GHRH by DPP4.&#xD;
      DPP4 inhibitors are currently approved therapies for the treatment of hyperglycemia in&#xD;
      patients with type 2 diabetes mellitus. They additionally cause blood vessel relaxation. We&#xD;
      therefore propose to test the hypothesis that DPP4 inhibition simultaneously enhances GH&#xD;
      secretion while improving blood glucoses and vascular function in patient populations with&#xD;
      low GH and increased cardiovascular risk. These preliminary aims serve primarily as a novel&#xD;
      &quot;proof of concept&quot; study to define the effect of acute pharmacologic DPPIV inhibition on&#xD;
      stimulated GH secretion.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2013</start_date>
  <completion_date type="Actual">May 2017</completion_date>
  <primary_completion_date type="Actual">May 2017</primary_completion_date>
  <phase>Phase 4</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>Other</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Aim 1: Stimulated Peak Growth Hormone Level</measure>
    <time_frame>Growth Hormone Level at 30 minutes (i.e. at completion of arginine infusion), 45 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes</time_frame>
    <description>Subjects underwent two study days separated by a washout period. On one study day they will receive sitagliptin and on another placebo, in a randomized double-blind fashion. Growth hormone secretion was stimulated using arginine (30 grams i.v. over 30 minutes) on each study day. Growth hormone levels were assessed during a 3 hour period following arginine stimulation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Aim 1: Percent Change From Baseline in Forearm Vascular Resistance</measure>
    <time_frame>Percent change from baseline in forearm vascular resistance at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes</time_frame>
    <description>Forearm blood flow was determined by strain gauge plethysmography. Forearm vascular resistance was then calculated by dividing this into mean arterial pressure. The percent change from baseline was determined at each timepoint.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Aim 1: Percent Change From Baseline in Forearm Blood Flow</measure>
    <time_frame>Percent change from baseline in forearm blood flow at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes.</time_frame>
    <description>Forearm blood flow was determined by strain gauge plethysmography. The percent change from baseline was determined at each timepoint.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Aim 2: Percent Change From Baseline in Forearm Blood Flow</measure>
    <time_frame>Percent change from baseline in forearm blood flow at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes.</time_frame>
    <description>Subjects undergo two study days separated by a washout period. On one study day they received sitagliptin plus another study drug and on another sitagliptin plus placebo, in a randomized double-blind fashion. Forearm blood flow was assessed at each visit.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Aim 2: Percent Change From Baseline in Forearm Vascular Resistance</measure>
    <time_frame>Percent change from baseline in forearm vascular resistance at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes</time_frame>
    <description>Subjects undergo two study days separated by a washout period. On one study day they will receive sitagliptin plus another study drug and on another sitagliptin plus placebo, in a randomized double-blind fashion. Forearm blood flow was assessed at each visit every 30 minutes for 3 hours. This was divided into mean arterial pressure to determine forearm vascular resistance.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels</measure>
    <time_frame>baseline and every 30 minutes for 180 minutes</time_frame>
    <description>In Aim 1 subjects underwent two study days separated by a washout period. On one study day they received study drug and on another placebo, in a randomized double-blind fashion. Venous blood samples were obtained at each visit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Aim 2: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels</measure>
    <time_frame>baseline and every 30 minutes until 180 minutes</time_frame>
    <description>Subjects undergo two study days separated by a washout period. On one study day they received sitagliptin plus pegvisomant and on another sitagliptin plus placebo, in a randomized double-blind fashion. Tissue plasminogen activator activity (tPA) was assessed at each visit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Aim 2: Measurement of Growth Hormone (GH) Levels</measure>
    <time_frame>baseline and every 30 minutes until 180 minutes</time_frame>
    <description>Subjects undergo two study days separated by a washout period. On one study day they received sitagliptin plus pegvisomant and on another sitagliptin plus placebo, in a randomized double-blind fashion. Growth hormone secretion following arginine stimulation was assessed at each visit. Growth hormone levels were determined using an assay that is not subject to interference by pegvisomant.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">44</enrollment>
  <condition>Obesity</condition>
  <arm_group>
    <arm_group_label>Group A (14 healthy subjects)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>In Aim 1: Healthy Lean adults are randomized in a double-blinded cross over fashion to sitagliptin versus placebo.&#xD;
In Aim 2: Healthy Lean adults receive sitagliptin and are randomized in a double-blinded cross over fashion to pre-treatment with either LNMMA (L-N-Monomethyl-arginine) versus placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B (14 healthy subjects)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>In Aim 1: Healthy Lean adults are randomized in a double-blinded cross over fashion to sitagliptin versus placebo.&#xD;
In Aim 2: Healthy Lean adults receive sitagliptin and are randomized in a double-blinded cross over fashion to pre-treatment with either pegvisomant versus placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group C (14 healthy subjects)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>In Aim 1: Healthy Lean adults are randomized in a double-blinded cross over fashion to sitagliptin versus placebo.&#xD;
In Aim 2: Healthy Lean adults receive sitagliptin and are randomized in a double-blinded cross over fashion to pre-treatment with either Exendin 9-39 versus placebo.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sitagliptin</intervention_name>
    <description>During Aim 1, given on one of two study days (other study day subjects receive placebo.) During Aim 2, given during both of two study days.</description>
    <arm_group_label>Group A (14 healthy subjects)</arm_group_label>
    <arm_group_label>Group B (14 healthy subjects)</arm_group_label>
    <arm_group_label>Group C (14 healthy subjects)</arm_group_label>
    <other_name>Januvia</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pegvisomant</intervention_name>
    <description>During Aim 2, given 72 hours prior to one of two study days (Group B subjects only)</description>
    <arm_group_label>Group B (14 healthy subjects)</arm_group_label>
    <other_name>Somavert</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>During Aim 1, given on one of two study days (other study day subjects receive sitagliptin.) During Aim 2, given on one of two study days (other study day subjects receive either L-NMMA, pegvisomant, or Exendin 9-39 pending their group assignment)</description>
    <arm_group_label>Group A (14 healthy subjects)</arm_group_label>
    <arm_group_label>Group B (14 healthy subjects)</arm_group_label>
    <arm_group_label>Group C (14 healthy subjects)</arm_group_label>
    <other_name>sugar pill</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>L-NMMA</intervention_name>
    <description>During Aim 2, given during one of two study days (Group A subjects only)</description>
    <arm_group_label>Group A (14 healthy subjects)</arm_group_label>
    <other_name>L-N-Monomethyl-arginine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Exendin 9-39</intervention_name>
    <description>During Aim 2, given during one of two study days (Group C subjects only)</description>
    <arm_group_label>Group C (14 healthy subjects)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 to 40 years inclusive&#xD;
&#xD;
          -  BMI ≤ 25 kg/m2&#xD;
&#xD;
          -  For female subjects:&#xD;
&#xD;
        Status-post surgical sterilization, or If of child-bearing potential, utilization of a&#xD;
        barrier method of birth control following negative serum pregnancy test at screening visit&#xD;
        and on every study day&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Smoking&#xD;
&#xD;
          -  Type 1 or Type 2 Diabetes Mellitus, as defined by a fasting glucose of 126 mg/dL or&#xD;
             greater at the time of screening visit or the use of anti-diabetic medication&#xD;
&#xD;
          -  Hypertension, as defined by an untreated seated systolic blood pressure (SBP) greater&#xD;
             than 140 mmHg and/or an untreated diastolic blood pressure (DBP) greater than 90 mmHg&#xD;
             at the time of screening visit or the use of anti-hypertensive medication&#xD;
&#xD;
          -  History of reported or recorded hypoglycemia (plasma glucose &lt; 70 mg/dL)&#xD;
&#xD;
          -  Pregnancy and/or Breast-Feeding&#xD;
&#xD;
          -  Use of any medication other than multivitamin, including use of transdermal as well as&#xD;
             oral hormone replacement therapy or use of oral contraceptive therapy&#xD;
&#xD;
          -  Anemia defined as hematocrit &lt;35% at screening visit&#xD;
&#xD;
          -  Cardiovascular or cerebrovascular disease, including history of myocardial infarction,&#xD;
             history of congestive heart failure, history of stroke&#xD;
&#xD;
          -  Pulmonary Hypertension&#xD;
&#xD;
          -  Abnormal thyroid hormone levels (TSH) at the time of screening visit&#xD;
&#xD;
          -  Abnormal serum insulin like growth factor-1 (IGF-1) at the time of screening visit&#xD;
&#xD;
          -  Impaired renal function, defined as estimated glomerular filtration rate (eGFR) &lt;60&#xD;
             mL/min/1.73 m^2&#xD;
&#xD;
          -  Impaired hepatic function (alanine or aspartate transaminase &gt; 2 X upper limit of&#xD;
             normal range)&#xD;
&#xD;
          -  Treatment with an investigational drug in the 1 month preceding the study&#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>Jessica K Devin, MD, MSCI</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vanderbilt University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>October 3, 2012</study_first_submitted>
  <study_first_submitted_qc>October 3, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 5, 2012</study_first_posted>
  <results_first_submitted>January 18, 2018</results_first_submitted>
  <results_first_submitted_qc>May 25, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">May 29, 2018</results_first_posted>
  <last_update_submitted>May 25, 2018</last_update_submitted>
  <last_update_submitted_qc>May 25, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 29, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Vanderbilt University</investigator_affiliation>
    <investigator_full_name>Jessica Koch Devin</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>obesity</keyword>
  <keyword>growth hormone</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Obesity</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sitagliptin Phosphate</mesh_term>
  </intervention_browse>
  <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>September 8, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/73/NCT01701973/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Healthy Lean Adults are randomized to two cross-over studies (Aim 1 and Aim 2).</recruitment_details>
      <pre_assignment_details>In Aim 1, Healthy adults were randomized in a double-blinded cross-over fashion to sitagliptin vs placebo. A minimum 8 week wash-out separated Aims 1 &amp; 2. 23 of the same adults who completed Aim 1 participated in Aim 2. In Aim 2, these adults were divided into three subgroups and randomized to sitagliptin+placebo vs. sitagliptin+antagonist.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Aim 1: Sitagliptin, Then Placebo</title>
          <description>In Aim 1: Healthy Lean adults are randomized in a double-blinded cross over fashion to sitagliptin versus placebo.</description>
        </group>
        <group group_id="P2">
          <title>Aim 1: Placebo, Then Sitagliptin</title>
          <description>In Aim 1: Healthy Lean adults are randomized in a double-blinded cross over fashion to sitagliptin versus placebo.</description>
        </group>
        <group group_id="P3">
          <title>Aim 2: Sitagliptin + Placebo,Then Sitagliptin + LNMMA</title>
          <description>In Aim 2: Healthy Lean adults receive sitagliptin and are randomized in a double-blinded cross over fashion to pre-treatment with either L-NMMA (L-N-Monomethyl-arginine) versus placebo.</description>
        </group>
        <group group_id="P4">
          <title>Aim 2:Sitagliptin + LNMMA, Then Sitagliptin + Placebo</title>
          <description>In Aim 2: Healthy Lean adults receive sitagliptin and are randomized in a double-blinded cross over fashion to pre-treatment with either L-NMMA (L-N-Monomethyl-arginine) versus placebo.</description>
        </group>
        <group group_id="P5">
          <title>Aim 2: Sitagliptin + Placebo, Then Sitagliptin + Pegvisomant</title>
          <description>In Aim 2: Healthy Lean adults receive sitagliptin and are randomized in a double-blinded cross over fashion to pre-treatment with either pegvisomant versus placebo.</description>
        </group>
        <group group_id="P6">
          <title>Aim 2: Sitagliptin + Pegvisomant, Then Sitagliptin + Placebo</title>
          <description>In Aim 2: Healthy Lean adults receive sitagliptin and are randomized in a double-blinded cross over fashion to pre-treatment with either pegvisomant versus placebo.</description>
        </group>
        <group group_id="P7">
          <title>Aim 2: Sitagliptin + Placebo, Then Sitagliptin + Exendin 9-39</title>
          <description>In Aim 2: Healthy Lean adults receive sitagliptin and are randomized in a double-blinded cross over fashion to pre-treatment with either Exendin 9-39 versus placebo.</description>
        </group>
        <group group_id="P8">
          <title>Aim 2: Sitagliptin + Exendin 9-39, Then Sitagliptin + Placebo</title>
          <description>In Aim 2: Healthy Lean adults receive sitagliptin and are randomized in a double-blinded cross over fashion to pre-treatment with either Exendin 9-39 versus placebo.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Aim 1: First Intervention (1 Day)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="23"/>
                <participants group_id="P2" count="21"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="23"/>
                <participants group_id="P2" count="20"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Aim 1: Second Intervention (1 Day)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="22">1 subject was lost to follow-up in between Periods 1 and 2.</participants>
                <participants group_id="P2" count="17">3 subjects were lost to follow-up in between Periods 1 and 2.</participants>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="17"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Aim 2: First Intervention (1 Day)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="4"/>
                <participants group_id="P5" count="2"/>
                <participants group_id="P6" count="3"/>
                <participants group_id="P7" count="5"/>
                <participants group_id="P8" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="4"/>
                <participants group_id="P5" count="2"/>
                <participants group_id="P6" count="3"/>
                <participants group_id="P7" count="5"/>
                <participants group_id="P8" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Aim 2: Second Intervention (1 Day)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="4"/>
                <participants group_id="P5" count="2"/>
                <participants group_id="P6" count="3"/>
                <participants group_id="P7" count="5"/>
                <participants group_id="P8" count="3">1 subject was lost to follow-up in between Periods 3 and 4.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="4"/>
                <participants group_id="P5" count="2"/>
                <participants group_id="P6" count="3"/>
                <participants group_id="P7" count="5"/>
                <participants group_id="P8" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
                <participants group_id="P8" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Participants From All Groups</title>
          <description>Data was collected as one group</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="39"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25" spread="5"/>
                  </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>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" 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>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Aim 1: Stimulated Peak Growth Hormone Level</title>
        <description>Subjects underwent two study days separated by a washout period. On one study day they will receive sitagliptin and on another placebo, in a randomized double-blind fashion. Growth hormone secretion was stimulated using arginine (30 grams i.v. over 30 minutes) on each study day. Growth hormone levels were assessed during a 3 hour period following arginine stimulation.</description>
        <time_frame>Growth Hormone Level at 30 minutes (i.e. at completion of arginine infusion), 45 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes</time_frame>
        <population>Data from all subjects who completed both study days in Aim 1 were analyzed. Subjects represented young, healthy adults without any chronic medical conditions and who did not take any medications. Oral birth control use was not permitted.</population>
        <group_list>
          <group group_id="O1">
            <title>Aim 1: Sitagliptin,Female Participants</title>
            <description>Subjects underwent two study days separated by a washout period. On one study day they received sitagliptin and on another placebo, in a randomized double-blind fashion. Growth hormone secretion was stimulated using arginine on each study day. Growth hormone levels were assessed during a 3 hour period following arginine stimulation.</description>
          </group>
          <group group_id="O2">
            <title>Aim 1: Placebo, Female Participants</title>
            <description>Subjects underwent two study days separated by a washout period. On one study day they received sitagliptin and on another placebo, in a randomized double-blind fashion. Growth hormone secretion was stimulated using arginine on each study day. Growth hormone levels were assessed during a 3 hour period following arginine stimulation.</description>
          </group>
          <group group_id="O3">
            <title>Aim 1: Sitagliptin, Male Participants</title>
            <description>Subjects underwent two study days separated by a washout period. On one study day they received sitagliptin and on another placebo, in a randomized double-blind fashion. Growth hormone secretion was stimulated using arginine on each study day. Growth hormone levels were assessed during a 3 hour period following arginine stimulation.</description>
          </group>
          <group group_id="O4">
            <title>Aim 1: Placebo, Male Participants</title>
            <description>Subjects underwent two study days separated by a washout period. On one study day they received sitagliptin and on another placebo, in a randomized double-blind fashion. Growth hormone secretion was stimulated using arginine on each study day. Growth hormone levels were assessed during a 3 hour period following arginine stimulation.</description>
          </group>
        </group_list>
        <measure>
          <title>Aim 1: Stimulated Peak Growth Hormone Level</title>
          <description>Subjects underwent two study days separated by a washout period. On one study day they will receive sitagliptin and on another placebo, in a randomized double-blind fashion. Growth hormone secretion was stimulated using arginine (30 grams i.v. over 30 minutes) on each study day. Growth hormone levels were assessed during a 3 hour period following arginine stimulation.</description>
          <population>Data from all subjects who completed both study days in Aim 1 were analyzed. Subjects represented young, healthy adults without any chronic medical conditions and who did not take any medications. Oral birth control use was not permitted.</population>
          <units>ng/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="29"/>
                <count group_id="O3" value="10"/>
                <count group_id="O4" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>30 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.2" spread="4.2"/>
                    <measurement group_id="O2" value="3.1" spread="3.3"/>
                    <measurement group_id="O3" value="1.9" spread="1.9"/>
                    <measurement group_id="O4" value="2.0" spread="2.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>45 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.5" spread="6.1"/>
                    <measurement group_id="O2" value="6.6" spread="5.0"/>
                    <measurement group_id="O3" value="3.4" spread="3.5"/>
                    <measurement group_id="O4" value="3.9" spread="3.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>60 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.4" spread="6.4"/>
                    <measurement group_id="O2" value="7.0" spread="6.0"/>
                    <measurement group_id="O3" value="3.0" spread="3.6"/>
                    <measurement group_id="O4" value="3.3" spread="2.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>90 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.0" spread="3.4"/>
                    <measurement group_id="O2" value="6.4" spread="4.8"/>
                    <measurement group_id="O3" value="1.1" spread="1.00"/>
                    <measurement group_id="O4" value="2.1" spread="2.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>120 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.7" spread="2.1"/>
                    <measurement group_id="O2" value="4.2" spread="3.4"/>
                    <measurement group_id="O3" value="1.5" spread="3.1"/>
                    <measurement group_id="O4" value="0.9" spread="0.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>150 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.8" spread="2.5"/>
                    <measurement group_id="O2" value="2.4" spread="2.1"/>
                    <measurement group_id="O3" value="2.2" spread="4.3"/>
                    <measurement group_id="O4" value="1.8" spread="3.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>180 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.9" spread="0.9"/>
                    <measurement group_id="O2" value="1.3" spread="1.9"/>
                    <measurement group_id="O3" value="1.0" spread="1.9"/>
                    <measurement group_id="O4" value="1.0" spread="1.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Aim 1: Percent Change From Baseline in Forearm Vascular Resistance</title>
        <description>Forearm blood flow was determined by strain gauge plethysmography. Forearm vascular resistance was then calculated by dividing this into mean arterial pressure. The percent change from baseline was determined at each timepoint.</description>
        <time_frame>Percent change from baseline in forearm vascular resistance at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Aim 1: Sitagliptin,Female Participants</title>
            <description>Subjects underwent two study days separated by a washout period. On one study day they received sitagliptin and on another placebo, in a randomized double-blind fashion. Growth hormone secretion was stimulated using arginine on each study day. Forearm vascular resistance (FVR) was assessed during a 3 hour period following arginine stimulation.</description>
          </group>
          <group group_id="O2">
            <title>Aim 1: Placebo, Female Participants</title>
            <description>Subjects underwent two study days separated by a washout period. On one study day they received sitagliptin and on another placebo, in a randomized double-blind fashion. Growth hormone secretion was stimulated using arginine on each study day. Forearm vascular resistance (FVR) was assessed during a 3 hour period following arginine stimulation.</description>
          </group>
          <group group_id="O3">
            <title>Aim 1: Sitagliptin, Male Participants</title>
            <description>Subjects underwent two study days separated by a washout period. On one study day they received sitagliptin and on another placebo, in a randomized double-blind fashion. Growth hormone secretion was stimulated using arginine on each study day. Forearm vascular resistance (FVR) was assessed during a 3 hour period following arginine stimulation.</description>
          </group>
          <group group_id="O4">
            <title>Aim 1: Placebo, Male Participants</title>
            <description>Subjects underwent two study days separated by a washout period. On one study day they received sitagliptin and on another placebo, in a randomized double-blind fashion. Growth hormone secretion was stimulated using arginine on each study day. Forearm vascular resistance (FVR) was assessed during a 3 hour period following arginine stimulation.</description>
          </group>
        </group_list>
        <measure>
          <title>Aim 1: Percent Change From Baseline in Forearm Vascular Resistance</title>
          <description>Forearm blood flow was determined by strain gauge plethysmography. Forearm vascular resistance was then calculated by dividing this into mean arterial pressure. The percent change from baseline was determined at each timepoint.</description>
          <units>percentage change from baseline</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="29"/>
                <count group_id="O3" value="10"/>
                <count group_id="O4" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>30 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.0677" spread="18.56794"/>
                    <measurement group_id="O2" value="-5.3498" spread="19.60881"/>
                    <measurement group_id="O3" value="1.4929" spread="21.57596"/>
                    <measurement group_id="O4" value="-11.2235" spread="13.60628"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>60 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.1365" spread="16.61555"/>
                    <measurement group_id="O2" value="-1.0195" spread="22.62776"/>
                    <measurement group_id="O3" value="6.7355" spread="23.96889"/>
                    <measurement group_id="O4" value="4.6875" spread="31.77169"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>90 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.1867" spread="22.00489"/>
                    <measurement group_id="O2" value="-1.6694" spread="31.84989"/>
                    <measurement group_id="O3" value="1.0144" spread="28.50393"/>
                    <measurement group_id="O4" value="-3.8029" spread="35.33295"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>120 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-12.5192" spread="31.29272"/>
                    <measurement group_id="O2" value="-5.0763" spread="26.06546"/>
                    <measurement group_id="O3" value="-10.3674" spread="32.22945"/>
                    <measurement group_id="O4" value="-2.7449" spread="31.52281"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>150 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-24.1962" spread="23.92090"/>
                    <measurement group_id="O2" value="-11.8335" spread="27.88447"/>
                    <measurement group_id="O3" value="-9.7129" spread="30.40280"/>
                    <measurement group_id="O4" value="-7.1590" spread="30.41909"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>180 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-22.4043" spread="27.60020"/>
                    <measurement group_id="O2" value="-16.5358" spread="32.22119"/>
                    <measurement group_id="O3" value="-11.9609" spread="20.50786"/>
                    <measurement group_id="O4" value="-15.0591" spread="25.33331"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Aim 1: Percent Change From Baseline in Forearm Blood Flow</title>
        <description>Forearm blood flow was determined by strain gauge plethysmography. The percent change from baseline was determined at each timepoint.</description>
        <time_frame>Percent change from baseline in forearm blood flow at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes.</time_frame>
        <population>Data from all subjects who completed both study days in Aim 1 were analyzed. Subjects represented young, healthy adults without any chronic medical conditions and who did not take any medications. Oral birth control use was not permitted.</population>
        <group_list>
          <group group_id="O1">
            <title>Aim 1: Sitagliptin,Female Participants</title>
            <description>Subjects underwent two study days separated by a washout period. On one study day they received sitagliptin and on another placebo, in a randomized double-blind fashion. Growth hormone secretion was stimulated using arginine on each study day. Forearm blood flow was assessed during a 3 hour period following arginine stimulation.</description>
          </group>
          <group group_id="O2">
            <title>Aim 1: Placebo, Female Participants</title>
            <description>Subjects underwent two study days separated by a washout period. On one study day they received sitagliptin and on another placebo, in a randomized double-blind fashion. Growth hormone secretion was stimulated using arginine on each study day. Forearm blood flow was assessed during a 3 hour period following arginine stimulation.</description>
          </group>
          <group group_id="O3">
            <title>Aim 1: Sitagliptin, Male Participants</title>
            <description>Subjects underwent two study days separated by a washout period. On one study day they received sitagliptin and on another placebo, in a randomized double-blind fashion. Growth hormone secretion was stimulated using arginine on each study day. Forearm blood flow was assessed during a 3 hour period following arginine stimulation.</description>
          </group>
          <group group_id="O4">
            <title>Aim 1: Placebo, Male Participants</title>
            <description>Subjects underwent two study days separated by a washout period. On one study day they received sitagliptin and on another placebo, in a randomized double-blind fashion. Growth hormone secretion was stimulated using arginine on each study day. Forearm blood flow was assessed during a 3 hour period following arginine stimulation.</description>
          </group>
        </group_list>
        <measure>
          <title>Aim 1: Percent Change From Baseline in Forearm Blood Flow</title>
          <description>Forearm blood flow was determined by strain gauge plethysmography. The percent change from baseline was determined at each timepoint.</description>
          <population>Data from all subjects who completed both study days in Aim 1 were analyzed. Subjects represented young, healthy adults without any chronic medical conditions and who did not take any medications. Oral birth control use was not permitted.</population>
          <units>percent change from baseline</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="29"/>
                <count group_id="O3" value="10"/>
                <count group_id="O4" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>30 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4835" spread="19.44436"/>
                    <measurement group_id="O2" value="1.6458" spread="19.42502"/>
                    <measurement group_id="O3" value="-.0238" spread="23.86278"/>
                    <measurement group_id="O4" value="9.2597" spread="14.60368"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>60 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.3416" spread="21.33943"/>
                    <measurement group_id="O2" value="4.9101" spread="37.42841"/>
                    <measurement group_id="O3" value="-2.8869" spread="25.79685"/>
                    <measurement group_id="O4" value="0.6789" spread="24.91588"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>90 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.9192" spread="36.11077"/>
                    <measurement group_id="O2" value="11.7285" spread="47.44341"/>
                    <measurement group_id="O3" value="1.5212" spread="30.57639"/>
                    <measurement group_id="O4" value="13.5358" spread="37.76659"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>120 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.2248" spread="40.83970"/>
                    <measurement group_id="O2" value="10.3081" spread="28.31870"/>
                    <measurement group_id="O3" value="20.1185" spread="38.89402"/>
                    <measurement group_id="O4" value="9.9379" spread="28.93967"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>150 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39.9269" spread="45.00577"/>
                    <measurement group_id="O2" value="19.7355" spread="30.90766"/>
                    <measurement group_id="O3" value="21.6011" spread="42.67343"/>
                    <measurement group_id="O4" value="15.0944" spread="34.56449"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>180 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40.6354" spread="50.48606"/>
                    <measurement group_id="O2" value="30.0924" spread="36.51124"/>
                    <measurement group_id="O3" value="16.8489" spread="24.95539"/>
                    <measurement group_id="O4" value="26.1772" spread="34.75120"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Aim 2: Percent Change From Baseline in Forearm Blood Flow</title>
        <description>Subjects undergo two study days separated by a washout period. On one study day they received sitagliptin plus another study drug and on another sitagliptin plus placebo, in a randomized double-blind fashion. Forearm blood flow was assessed at each visit.</description>
        <time_frame>Percent change from baseline in forearm blood flow at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes.</time_frame>
        <population>19 of the original 29 females in Aim 1 returned to complete two more study days (Aim 2) in which they received sitagliptin + double-blinded study drug vs. sitagliptin plus placebo in a cross-over study. Three men from Aim 1 also returned to complete two more study days (Aim 2).</population>
        <group_list>
          <group group_id="O1">
            <title>Aim 2: Sitagliptin and LNMMA, Female Participants</title>
            <description>Seven of the original 29 women returned for an additional two study days separated by a wash-out period. On one study day they received sitagliptin plus L-N-monomethylarginine (LNMMA) and on another sitagliptin plus placebo, in a randomized cross-over fashion.</description>
          </group>
          <group group_id="O2">
            <title>Aim 2: Sitagliptin and Placebo, Females in LNMMA Group</title>
            <description>Seven of the original 29 women returned for an additional two study days separated by a wash-out period. On one study day they received sitagliptin plus L-N-monomethylarginine (LNMMA) and on another sitagliptin plus placebo, in a randomized cross-over fashion.</description>
          </group>
          <group group_id="O3">
            <title>Aim 2: Sitagliptin and LNMMA, Male Participants</title>
            <description>Two of the men in Aim 1 returned for an additional two study days separated by a wash-out period. On one study day they received sitagliptin plus L-N-monomethylarginine (LNMMA) and on another sitagliptin plus placebo, in a randomized cross-over fashion.</description>
          </group>
          <group group_id="O4">
            <title>Aim 2: Sitagliptin and Placebo, Males in LNMMA Group</title>
            <description>Two of the men in Aim 1 returned for an additional two study days separated by a wash-out period. On one study day they received sitagliptin plus L-N-monomethylarginine (LNMMA) and on another sitagliptin plus placebo, in a randomized cross-over fashion.</description>
          </group>
          <group group_id="O5">
            <title>Aim 2: Sitagliptin and Pegvisomant, Female Participants</title>
            <description>Five of the original 29 women returned for an additional two study days separated by a wash-out period. On one study day they received sitagliptin plus pegvisomant and on another sitagliptin plus placebo, in a randomized cross-over fashion. The protocol specified a priori not to study men further if the first seven men randomized to sitagliptin vs. placebo in Aim 1 showed no effect of sitagliptin in men.</description>
          </group>
          <group group_id="O6">
            <title>Aim 2: Sitagliptin &amp; Placebo, Females in Pegvisomant Group</title>
            <description>Five of the original 29 women returned for an additional two study days separated by a wash-out period. On one study day they received sitagliptin plus pegvisomant and on another sitagliptin plus placebo, in a randomized cross-over fashion. The protocol specified a priori not to study men further if the first seven men randomized to sitagliptin vs. placebo in Aim 1 showed no effect of sitagliptin in men.</description>
          </group>
          <group group_id="O7">
            <title>Aim 2: Sitagliptin and Exendin 9-39, Female Participants</title>
            <description>Seven of the original 29 women returned for an additional two study days separated by a wash-out period. On one study day they received sitagliptin plus Exendin 9-39 and on another sitagliptin plus placebo, in a randomized cross-over fashion.</description>
          </group>
          <group group_id="O8">
            <title>Aim 2: Sitagliptin and Placebo, Females in Exendin 9-39 Group</title>
            <description>Seven of the original 29 women returned for an additional two study days separated by a wash-out period. On one study day they received sitagliptin plus Exendin 9-39 and on another sitagliptin plus placebo, in a randomized cross-over fashion.</description>
          </group>
          <group group_id="O9">
            <title>Aim 2: Sitagliptin and Exendin 9-39, Male Participant</title>
            <description>One of the men from Aim 1 returned for an additional two study days separated by a wash-out period. On one study day they received sitagliptin plus Exendin 9-39 and on another sitagliptin plus placebo, in a randomized cross-over fashion.</description>
          </group>
          <group group_id="O10">
            <title>Aim 2: Sitagliptin and Placebo, Male in Exendin 9-39 Group</title>
            <description>One of the men from Aim 1 returned for an additional two study days separated by a wash-out period. On one study day they received sitagliptin plus Exendin 9-39 and on another sitagliptin plus placebo, in a randomized cross-over fashion.</description>
          </group>
        </group_list>
        <measure>
          <title>Aim 2: Percent Change From Baseline in Forearm Blood Flow</title>
          <description>Subjects undergo two study days separated by a washout period. On one study day they received sitagliptin plus another study drug and on another sitagliptin plus placebo, in a randomized double-blind fashion. Forearm blood flow was assessed at each visit.</description>
          <population>19 of the original 29 females in Aim 1 returned to complete two more study days (Aim 2) in which they received sitagliptin + double-blinded study drug vs. sitagliptin plus placebo in a cross-over study. Three men from Aim 1 also returned to complete two more study days (Aim 2).</population>
          <units>percent change from baseline</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="7"/>
                <count group_id="O3" value="2"/>
                <count group_id="O4" value="2"/>
                <count group_id="O5" value="5"/>
                <count group_id="O6" value="5"/>
                <count group_id="O7" value="7"/>
                <count group_id="O8" value="7"/>
                <count group_id="O9" value="1"/>
                <count group_id="O10" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>30 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.71" spread="6.75"/>
                    <measurement group_id="O2" value="-9.34" spread="8.60"/>
                    <measurement group_id="O3" value="5.17" spread="4.27"/>
                    <measurement group_id="O4" value="14.78" spread="14.78"/>
                    <measurement group_id="O5" value="15.64" spread="5.06"/>
                    <measurement group_id="O6" value="0.39" spread="8.93"/>
                    <measurement group_id="O7" value="-7.33" spread="8.66"/>
                    <measurement group_id="O8" value="-0.98" spread="12.08"/>
                    <measurement group_id="O9" value="-7.59" spread="NA">Cannot be determined with 1 participant.</measurement>
                    <measurement group_id="O10" value="-22.67" spread="NA">Cannot be determined with 1 participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>60 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.64" spread="12.68"/>
                    <measurement group_id="O2" value="-17.06" spread="12.93"/>
                    <measurement group_id="O3" value="7.05" spread="4.06"/>
                    <measurement group_id="O4" value="4.56" spread="0.97"/>
                    <measurement group_id="O5" value="6.58" spread="10.16"/>
                    <measurement group_id="O6" value="16.10" spread="12.79"/>
                    <measurement group_id="O7" value="-10.54" spread="8.53"/>
                    <measurement group_id="O8" value="6.95" spread="9.53"/>
                    <measurement group_id="O9" value="9.37" spread="NA">Cannot be determined with 1 participant.</measurement>
                    <measurement group_id="O10" value="-13.00" spread="NA">Cannot be determined with 1 participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>90 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.24" spread="10.02"/>
                    <measurement group_id="O2" value="-6.35" spread="16.60"/>
                    <measurement group_id="O3" value="25.69" spread="6.25"/>
                    <measurement group_id="O4" value="20.32" spread="12.83"/>
                    <measurement group_id="O5" value="36.96" spread="14.71"/>
                    <measurement group_id="O6" value="16.67" spread="33.39"/>
                    <measurement group_id="O7" value="2.23" spread="8.69"/>
                    <measurement group_id="O8" value="2.08" spread="11.60"/>
                    <measurement group_id="O9" value="5.36" spread="NA">Cannot be determined with 1 participant.</measurement>
                    <measurement group_id="O10" value="-18.33" spread="NA">Cannot be determined with 1 participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>120 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.22" spread="12.54"/>
                    <measurement group_id="O2" value="9.80" spread="18.23"/>
                    <measurement group_id="O3" value="32.92" spread="0.97"/>
                    <measurement group_id="O4" value="56.26" spread="55.06"/>
                    <measurement group_id="O5" value="54.10" spread="21.87"/>
                    <measurement group_id="O6" value="41.97" spread="31.29"/>
                    <measurement group_id="O7" value="31.10" spread="9.04"/>
                    <measurement group_id="O8" value="22.24" spread="11.14"/>
                    <measurement group_id="O9" value="16.52" spread="NA">Cannot be determined with 1 participant.</measurement>
                    <measurement group_id="O10" value="-22.00" spread="NA">Cannot be determined with 1 participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>150 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.09" spread="13.00"/>
                    <measurement group_id="O2" value="11.26" spread="28.45"/>
                    <measurement group_id="O3" value="26.27" spread="13.73"/>
                    <measurement group_id="O4" value="71.51" spread="76.00"/>
                    <measurement group_id="O5" value="59.08" spread="32.36"/>
                    <measurement group_id="O6" value="26.87" spread="17.56"/>
                    <measurement group_id="O7" value="29.48" spread="8.22"/>
                    <measurement group_id="O8" value="15.59" spread="8.26"/>
                    <measurement group_id="O9" value="45.98" spread="NA">Cannot be determined with 1 participant.</measurement>
                    <measurement group_id="O10" value="1.33" spread="NA">Cannot be determined with 1 participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>180 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.80" spread="15.85"/>
                    <measurement group_id="O2" value="17.12" spread="20.53"/>
                    <measurement group_id="O3" value="29.24" spread="35.21"/>
                    <measurement group_id="O4" value="65.31" spread="80.28"/>
                    <measurement group_id="O5" value="51.21" spread="26.07"/>
                    <measurement group_id="O6" value="43.51" spread="26.31"/>
                    <measurement group_id="O7" value="30.76" spread="8.88"/>
                    <measurement group_id="O8" value="27.11" spread="12.21"/>
                    <measurement group_id="O9" value="54.91" spread="NA">Cannot be determined with 1 participant.</measurement>
                    <measurement group_id="O10" value="-1.67" spread="NA">Cannot be determined with 1 participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Aim 2: Percent Change From Baseline in Forearm Vascular Resistance</title>
        <description>Subjects undergo two study days separated by a washout period. On one study day they will receive sitagliptin plus another study drug and on another sitagliptin plus placebo, in a randomized double-blind fashion. Forearm blood flow was assessed at each visit every 30 minutes for 3 hours. This was divided into mean arterial pressure to determine forearm vascular resistance.</description>
        <time_frame>Percent change from baseline in forearm vascular resistance at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes</time_frame>
        <population>19 of the original 29 females who participated in Aim 1 returned to complete an additional two study days (Aim 2) in which they received sitagliptin + double-blinded study drug vs. sitagliptin plus placebo in a cross-over study. Three men from Aim 1 also returned to complete two more study days (Aim 2).</population>
        <group_list>
          <group group_id="O1">
            <title>Aim 2: Sitagliptin and LNMMA, Female Participants</title>
            <description>Seven of the original 29 women returned for an additional two study days separated by a wash-out period. On one study day they received sitagliptin plus LNMMA and on another sitagliptin plus placebo, in a randomized cross-over fashion.</description>
          </group>
          <group group_id="O2">
            <title>Aim 2: Sitagliptin and Placebo, Females in LNMMA Group</title>
            <description>Seven of the original 29 women returned for an additional two study days separated by a wash-out period. On one study day they received sitagliptin plus LNMMA and on another sitagliptin plus placebo, in a randomized cross-over fashion.</description>
          </group>
          <group group_id="O3">
            <title>Aim 2: Sitagliptin and LNMMA, Male Participants</title>
            <description>Two of the men in Aim 1 returned for an additional two study days separated by a wash-out period. On one study day they received sitagliptin plus L-N-monomethylarginine (LNMMA) and on another sitagliptin plus placebo, in a randomized cross-over fashion.</description>
          </group>
          <group group_id="O4">
            <title>Aim 2: Sitagliptin and Placebo, Males in LNMMA Group</title>
            <description>Two of the men in Aim 1 returned for an additional two study days separated by a wash-out period. On one study day they received sitagliptin plus L-N-monomethylarginine (LNMMA) and on another sitagliptin plus placebo, in a randomized cross-over fashion.</description>
          </group>
          <group group_id="O5">
            <title>Aim 2: Sitagliptin and Pegvisomant, Female Participants</title>
            <description>Five of the original 29 women returned for an additional two study days separated by a wash-out period. On one study day they received sitagliptin plus pegvisomant and on another sitagliptin plus placebo, in a randomized cross-over fashion. The protocol specified a priori not to study men further if the first seven men randomized to sitagliptin vs. placebo in Aim 1 showed no effect of sitagliptin in men.</description>
          </group>
          <group group_id="O6">
            <title>Aim 2: Sitagliptin &amp; Placebo,Females in Pegvisomant Group</title>
            <description>Five of the original 29 women returned for an additional two study days separated by a wash-out period. On one study day they received sitagliptin plus pegvisomant and on another sitagliptin plus placebo, in a randomized cross-over fashion. The protocol specified a priori not to study men further if the first seven men randomized to sitagliptin vs. placebo in Aim 1 showed no effect of sitagliptin in men.</description>
          </group>
          <group group_id="O7">
            <title>Aim 2: Sitagliptin and Exendin 9-39, Female Participants</title>
            <description>Seven of the original 29 women returned for an additional two study days separated by a wash-out period. On one study day they received sitagliptin plus Exendin 9-39 and on another sitagliptin plus placebo, in a randomized cross-over fashion.</description>
          </group>
          <group group_id="O8">
            <title>Aim 2: Sitagliptin and Placebo, Females in Exendin 9-39 Group</title>
            <description>Seven of the original 29 women returned for an additional two study days separated by a wash-out period. On one study day they received sitagliptin plus Exendin 9-39 and on another sitagliptin plus placebo, in a randomized cross-over fashion.</description>
          </group>
          <group group_id="O9">
            <title>Aim 2: Sitagliptin and Exendin 9-39, Male Participant</title>
            <description>One of the men in Aim 1 returned for an additional two study days separated by a wash-out period. On one study day they received sitagliptin plus Exendin 9-39 and on another sitagliptin plus placebo, in a randomized cross-over fashion.</description>
          </group>
          <group group_id="O10">
            <title>Aim 2: Sitagliptin and Placebo, Male in Exendin 9-39 Group</title>
            <description>One of the men in Aim 1 returned for an additional two study days separated by a wash-out period. On one study day they received sitagliptin plus Exendin 9-39 and on another sitagliptin plus placebo, in a randomized cross-over fashion.</description>
          </group>
        </group_list>
        <measure>
          <title>Aim 2: Percent Change From Baseline in Forearm Vascular Resistance</title>
          <description>Subjects undergo two study days separated by a washout period. On one study day they will receive sitagliptin plus another study drug and on another sitagliptin plus placebo, in a randomized double-blind fashion. Forearm blood flow was assessed at each visit every 30 minutes for 3 hours. This was divided into mean arterial pressure to determine forearm vascular resistance.</description>
          <population>19 of the original 29 females who participated in Aim 1 returned to complete an additional two study days (Aim 2) in which they received sitagliptin + double-blinded study drug vs. sitagliptin plus placebo in a cross-over study. Three men from Aim 1 also returned to complete two more study days (Aim 2).</population>
          <units>percent change from baseline</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="7"/>
                <count group_id="O3" value="2"/>
                <count group_id="O4" value="2"/>
                <count group_id="O5" value="5"/>
                <count group_id="O6" value="5"/>
                <count group_id="O7" value="7"/>
                <count group_id="O8" value="7"/>
                <count group_id="O9" value="1"/>
                <count group_id="O10" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>30 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.67" spread="9.66"/>
                    <measurement group_id="O2" value="8.98" spread="12.07"/>
                    <measurement group_id="O3" value="-9.87" spread="0.82"/>
                    <measurement group_id="O4" value="-14.60" spread="12.22"/>
                    <measurement group_id="O5" value="-20.00" spread="3.67"/>
                    <measurement group_id="O6" value="-3.75" spread="12.43"/>
                    <measurement group_id="O7" value="5.30" spread="8.19"/>
                    <measurement group_id="O8" value="4.53" spread="12.62"/>
                    <measurement group_id="O9" value="0.57" spread="NA">Cannot be determined with 1 participant.</measurement>
                    <measurement group_id="O10" value="27.77" spread="NA">Cannot be determined with 1 participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>60 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.77" spread="17.03"/>
                    <measurement group_id="O2" value="51.82" spread="36.73"/>
                    <measurement group_id="O3" value="-9.75" spread="2.28"/>
                    <measurement group_id="O4" value="-2.42" spread="3.34"/>
                    <measurement group_id="O5" value="-4.05" spread="10.67"/>
                    <measurement group_id="O6" value="-10.97" spread="11.64"/>
                    <measurement group_id="O7" value="14.46" spread="11.08"/>
                    <measurement group_id="O8" value="-4.26" spread="7.26"/>
                    <measurement group_id="O9" value="-11.80" spread="NA">Cannot be determined with 1 participant.</measurement>
                    <measurement group_id="O10" value="6.73" spread="NA">Cannot be determined with 1 participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>90 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.89" spread="8.93"/>
                    <measurement group_id="O2" value="39.24" spread="35.45"/>
                    <measurement group_id="O3" value="-23.34" spread="8.00"/>
                    <measurement group_id="O4" value="-16.75" spread="4.25"/>
                    <measurement group_id="O5" value="-25.28" spread="7.02"/>
                    <measurement group_id="O6" value="3.79" spread="19.09"/>
                    <measurement group_id="O7" value="1.76" spread="8.96"/>
                    <measurement group_id="O8" value="4.82" spread="16.53"/>
                    <measurement group_id="O9" value="-14.02" spread="NA">Cannot be determined with 1 participant.</measurement>
                    <measurement group_id="O10" value="22.45" spread="NA">Cannot be determined with 1 participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>120 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.99" spread="11.00"/>
                    <measurement group_id="O2" value="21.98" spread="35.57"/>
                    <measurement group_id="O3" value="-24.81" spread="1.18"/>
                    <measurement group_id="O4" value="-28.34" spread="21.27"/>
                    <measurement group_id="O5" value="-32.39" spread="8.90"/>
                    <measurement group_id="O6" value="-14.57" spread="18.78"/>
                    <measurement group_id="O7" value="-22.37" spread="6.11"/>
                    <measurement group_id="O8" value="-13.16" spread="10.34"/>
                    <measurement group_id="O9" value="-16.20" spread="NA">Cannot be determined with 1 participant.</measurement>
                    <measurement group_id="O10" value="26.68" spread="NA">Cannot be determined with 1 participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>150 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-13.25" spread="8.49"/>
                    <measurement group_id="O2" value="42.27" spread="44.03"/>
                    <measurement group_id="O3" value="-20.62" spread="6.34"/>
                    <measurement group_id="O4" value="-32.11" spread="24.34"/>
                    <measurement group_id="O5" value="-30.12" spread="11.10"/>
                    <measurement group_id="O6" value="-14.25" spread="13.15"/>
                    <measurement group_id="O7" value="-20.92" spread="5.30"/>
                    <measurement group_id="O8" value="-8.49" spread="9.03"/>
                    <measurement group_id="O9" value="-32.30" spread="NA">Cannot be determined with 1 participant.</measurement>
                    <measurement group_id="O10" value="-1.32" spread="NA">Cannot be determined with 1 participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>180 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.25" spread="10.76"/>
                    <measurement group_id="O2" value="5.28" spread="19.22"/>
                    <measurement group_id="O3" value="-22.56" spread="13.90"/>
                    <measurement group_id="O4" value="-19.52" spread="37.12"/>
                    <measurement group_id="O5" value="-25.00" spread="11.92"/>
                    <measurement group_id="O6" value="-17.97" spread="15.66"/>
                    <measurement group_id="O7" value="-22.58" spread="5.82"/>
                    <measurement group_id="O8" value="-16.76" spread="8.94"/>
                    <measurement group_id="O9" value="-34.69" spread="NA">Cannot be determined with 1 participant.</measurement>
                    <measurement group_id="O10" value="1.69" spread="NA">Cannot be determined with 1 participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels</title>
        <description>In Aim 1 subjects underwent two study days separated by a washout period. On one study day they received study drug and on another placebo, in a randomized double-blind fashion. Venous blood samples were obtained at each visit.</description>
        <time_frame>baseline and every 30 minutes for 180 minutes</time_frame>
        <population>Data from the first 14 subjects (7 men and 7 women) who completed both study days in Aim 1 were analyzed. We do not report tPA results from the remaining participants as the manufacturer changed the tPA assay standard and results were not comparable.</population>
        <group_list>
          <group group_id="O1">
            <title>Aim 1: Sitagliptin,Female Participants</title>
            <description>Subjects undergo two study days separated by a washout period. On one study day they received sitagliptin and on another placebo, in a randomized double-blind fashion. Growth hormone secretion was stimulated using arginine on each study day. tPA levels were assessed during a 3 hour period following arginine stimulation.</description>
          </group>
          <group group_id="O2">
            <title>Aim 1: Placebo, Female Participants</title>
            <description>Subjects underwent two study days separated by a washout period. On one study day they received sitagliptin and on another placebo, in a randomized double-blind fashion. Growth hormone secretion was stimulated using arginine on each study day. tPA levels were assessed during a 3 hour period following arginine stimulation.</description>
          </group>
          <group group_id="O3">
            <title>Aim 1: Sitagliptin, Male Participants</title>
            <description>Subjects underwent two study days separated by a washout period. On one study day they received sitagliptin and on another placebo, in a randomized double-blind fashion. Growth hormone secretion was stimulated using arginine on each study day. tPA levels were assessed during a 3 hour period following arginine stimulation.</description>
          </group>
          <group group_id="O4">
            <title>Aim 1: Placebo, Male Participants</title>
            <description>Subjects underwent two study days separated by a washout period. On one study day they received sitagliptin and on another placebo, in a randomized double-blind fashion. Growth hormone secretion was stimulated using arginine on each study day. tPA levels were assessed during a 3 hour period following arginine stimulation.</description>
          </group>
        </group_list>
        <measure>
          <title>Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels</title>
          <description>In Aim 1 subjects underwent two study days separated by a washout period. On one study day they received study drug and on another placebo, in a randomized double-blind fashion. Venous blood samples were obtained at each visit.</description>
          <population>Data from the first 14 subjects (7 men and 7 women) who completed both study days in Aim 1 were analyzed. We do not report tPA results from the remaining participants as the manufacturer changed the tPA assay standard and results were not comparable.</population>
          <units>IU/ml</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="7"/>
                <count group_id="O3" value="7"/>
                <count group_id="O4" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline prior to Arginine</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.30" spread="0.05"/>
                    <measurement group_id="O2" value="0.28" spread="0.05"/>
                    <measurement group_id="O3" value="0.44" spread="0.14"/>
                    <measurement group_id="O4" value="0.22" spread="0.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>30 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.40" spread="0.04"/>
                    <measurement group_id="O2" value="0.32" spread="0.04"/>
                    <measurement group_id="O3" value="0.28" spread="0.08"/>
                    <measurement group_id="O4" value="0.25" spread="0.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>45 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.43" spread="0.04"/>
                    <measurement group_id="O2" value="0.35" spread="0.04"/>
                    <measurement group_id="O3" value="0.40" spread="0.10"/>
                    <measurement group_id="O4" value="0.32" spread="0.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>60 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.40" spread="0.06"/>
                    <measurement group_id="O2" value="0.32" spread="0.05"/>
                    <measurement group_id="O3" value="0.37" spread="0.09"/>
                    <measurement group_id="O4" value="0.34" spread="0.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>90 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.39" spread="0.07"/>
                    <measurement group_id="O2" value="0.35" spread="0.06"/>
                    <measurement group_id="O3" value="0.34" spread="0.09"/>
                    <measurement group_id="O4" value="0.27" spread="0.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>120 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.40" spread="0.07"/>
                    <measurement group_id="O2" value="0.35" spread="0.04"/>
                    <measurement group_id="O3" value="0.38" spread="0.12"/>
                    <measurement group_id="O4" value="0.28" spread="0.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>150 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.44" spread="0.04"/>
                    <measurement group_id="O2" value="0.41" spread="0.04"/>
                    <measurement group_id="O3" value="0.42" spread="0.12"/>
                    <measurement group_id="O4" value="0.37" spread="0.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>180 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.55" spread="0.06"/>
                    <measurement group_id="O2" value="0.50" spread="0.05"/>
                    <measurement group_id="O3" value="0.51" spread="0.12"/>
                    <measurement group_id="O4" value="0.45" spread="0.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Aim 2: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels</title>
        <description>Subjects undergo two study days separated by a washout period. On one study day they received sitagliptin plus pegvisomant and on another sitagliptin plus placebo, in a randomized double-blind fashion. Tissue plasminogen activator activity (tPA) was assessed at each visit.</description>
        <time_frame>baseline and every 30 minutes until 180 minutes</time_frame>
        <population>Five of the original 29 women returned for two more study days separated by a wash-out. As pre-specified in the protocol, men did not complete this portion of the study. We do not report tPA results from participants who received LNMMA and Exendin 9-39 in this table as the manufacturer changed the tPA assay standard and results were not comparable.</population>
        <group_list>
          <group group_id="O1">
            <title>Aim 2: Sitagliptin and Placebo, Females in Pegvisomant Group</title>
            <description>Five of the original 29 women returned for an additional two study days separated by a wash-out period. On one study day they received sitagliptin plus pegvisomant and on another sitagliptin plus placebo, in a randomized cross-over fashion.</description>
          </group>
          <group group_id="O2">
            <title>Aim 2: Sitagliptin and Pegvisomant, Female Participants</title>
            <description>Five of the original 29 women returned for an additional two study days separated by a wash-out period. On one study day they received sitagliptin plus pegvisomant and on another sitagliptin plus placebo, in a randomized cross-over fashion.</description>
          </group>
        </group_list>
        <measure>
          <title>Aim 2: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels</title>
          <description>Subjects undergo two study days separated by a washout period. On one study day they received sitagliptin plus pegvisomant and on another sitagliptin plus placebo, in a randomized double-blind fashion. Tissue plasminogen activator activity (tPA) was assessed at each visit.</description>
          <population>Five of the original 29 women returned for two more study days separated by a wash-out. As pre-specified in the protocol, men did not complete this portion of the study. We do not report tPA results from participants who received LNMMA and Exendin 9-39 in this table as the manufacturer changed the tPA assay standard and results were not comparable.</population>
          <units>IU/ml</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline prior to Arginine</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.24" spread="0.05"/>
                    <measurement group_id="O2" value="0.10" spread="0.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>30 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.26" spread="0.04"/>
                    <measurement group_id="O2" value="0.15" spread="0.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>45 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.33" spread="0.06"/>
                    <measurement group_id="O2" value="0.17" spread="0.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>60 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.27" spread="0.08"/>
                    <measurement group_id="O2" value="0.14" spread="0.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>90 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.26" spread="0.07"/>
                    <measurement group_id="O2" value="0.16" spread="0.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>120 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.28" spread="0.08"/>
                    <measurement group_id="O2" value="0.16" spread="0.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>150 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.31" spread="0.07"/>
                    <measurement group_id="O2" value="0.20" spread="0.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>180 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.35" spread="0.06"/>
                    <measurement group_id="O2" value="0.23" spread="0.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Aim 2: Measurement of Growth Hormone (GH) Levels</title>
        <description>Subjects undergo two study days separated by a washout period. On one study day they received sitagliptin plus pegvisomant and on another sitagliptin plus placebo, in a randomized double-blind fashion. Growth hormone secretion following arginine stimulation was assessed at each visit. Growth hormone levels were determined using an assay that is not subject to interference by pegvisomant.</description>
        <time_frame>baseline and every 30 minutes until 180 minutes</time_frame>
        <population>Five of the original 29 women returned for an additional two study days separated by a wash-out period. As pre-specified in the protocol, men did not complete this portion of the study. We did not measure GH levels in participants who received LNMMA or Exendin 9-39 as these drugs are not known to influence GH secretion.</population>
        <group_list>
          <group group_id="O1">
            <title>Aim 2: Sitagliptin and Placebo, Females in Pegvisomant Group</title>
            <description>Five of the original 29 women returned for an additional two study days separated by a wash-out period. On one study day they received sitagliptin plus pegvisomant and on another sitagliptin plus placebo, in a randomized cross-over fashion.</description>
          </group>
          <group group_id="O2">
            <title>Aim 2: Sitagliptin and Pegvisomant, Female Participants</title>
            <description>Five of the original 29 women returned for an additional two study days separated by a wash-out period. On one study day they received sitagliptin plus pegvisomant and on another sitagliptin plus placebo, in a randomized cross-over fashion.</description>
          </group>
        </group_list>
        <measure>
          <title>Aim 2: Measurement of Growth Hormone (GH) Levels</title>
          <description>Subjects undergo two study days separated by a washout period. On one study day they received sitagliptin plus pegvisomant and on another sitagliptin plus placebo, in a randomized double-blind fashion. Growth hormone secretion following arginine stimulation was assessed at each visit. Growth hormone levels were determined using an assay that is not subject to interference by pegvisomant.</description>
          <population>Five of the original 29 women returned for an additional two study days separated by a wash-out period. As pre-specified in the protocol, men did not complete this portion of the study. We did not measure GH levels in participants who received LNMMA or Exendin 9-39 as these drugs are not known to influence GH secretion.</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>30 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.99" spread="1.60"/>
                    <measurement group_id="O2" value="4.27" spread="2.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>60 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.92" spread="2.37"/>
                    <measurement group_id="O2" value="7.00" spread="2.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>90 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.05" spread="2.39"/>
                    <measurement group_id="O2" value="11.53" spread="4.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>120 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.06" spread="2.18"/>
                    <measurement group_id="O2" value="6.17" spread="1.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>150 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.83" spread="0.83"/>
                    <measurement group_id="O2" value="4.09" spread="1.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>180 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.57" spread="0.82"/>
                    <measurement group_id="O2" value="1.77" spread="0.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>The first subject started drug 2/11/13 and the last completed 2/10/2017. In Aim 1, each subject took oral study drug (placebo vs. sitagliptin). Adverse event data was collected over a one month period for each subject. In Aim 2, each subject took oral sitagliptin and also received a single dose of LNMMA, Exendin 9-39 or Pegvisomant based upon their subgroup assigment. Adverse event data was collected over a 6 week period for each subject.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Sitagliptin</title>
          <description>Healthy lean adults completed a double blinded cross over study in which they took sitagliptin vs. placebo separated by a wash-out.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Healthy lean adults completed a double blinded cross over study in which they took sitagliptin vs. placebo separated by a wash-out.</description>
        </group>
        <group group_id="E3">
          <title>Sitagliptin Plus Pegvisomant</title>
          <description>Five women from Aim 1 returned for an additional two study days in which they were randomized to sitagliptin plus placebo vs. sitagliptin plus pre-treatment with pegvisomant.</description>
        </group>
        <group group_id="E4">
          <title>Sitagliptin Plus LNMMA</title>
          <description>9 participants from Aim 1 returned for an additional two study days in which they were randomized to sitagliptin plus placebo vs. sitagliptin plus L-N-mono-methylarginine (LNMMA).</description>
        </group>
        <group group_id="E5">
          <title>Sitagliptin Plus Exendin 9-39</title>
          <description>8 participants from Aim 1 returned for an additional two study days in which they were randomized to sitagliptin plus placebo vs. sitagliptin plus Exendin 9-39.</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="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="43"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="43"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
              </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="7" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="43"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="43"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Reflux</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="43"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Abdominal cramping and diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="43"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness and paresthesias during arginine infusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="43"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Bruising related to placement of intravenous catheter</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="43"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="8"/>
              </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>Dr. Jessica Devin</name_or_title>
      <organization>Vanderbilt University Medical Center</organization>
      <phone>6159361665</phone>
      <email>jessica.devin@vanderbilt.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/NCT01701973
org study id: 120078
secondary id: 1K23HL119602
nct id: NCT01701973
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
This study tests the following hypotheses:

      Aim 1: Test the hypothesis that acute dipeptidyl peptidase 4 (DPP4) inhibition with the
      currently available anti-diabetic drug, sitagliptin, will increase stimulated growth hormone
      (GH) secretion in healthy lean adults by decreasing the degradation of growth hormone
      releasing hormone (GHRH).

      Aim 2: Test the hypothesis that decreased degradation of GHRH during acute DPP4 inhibition
      will result in an increase in endothelium-dependent vasodilation mediated by GH and
      independent from GLP1 (glucagon like peptide-1) in healthy lean adults.

      This study promises to provide novel data regarding how this increasingly used class of
      anti-diabetic drugs affects the pituitary GH axis and could affect blood vessel relaxation.
      Growth hormone levels are low in the setting of obesity and pre-diabetes. A further study may
      evaluate the effect of chronic DPP4 inhibitor therapy in a population of patients with
      obesity and pre-diabetes.
Growth hormone secretion is low in patients with obesity, insulin resistance, and
      hyperlipidemia. GH therapy in these populations and others has been limited by side effects
      which include hyperglycemia. Another strategy to increase GH secretion is to enhance
      pulsatile GH secretion by growth hormone releasing hormone. Growth hormone releasing hormone
      (GHRH) has a half life of 5 minutes due to its rapid inactivation by DPP4. An alternative
      strategy to increase endogenous GH secretion is by inhibiting degradation of GHRH by DPP4.
      DPP4 inhibitors are currently approved therapies for the treatment of hyperglycemia in
      patients with type 2 diabetes mellitus. They additionally cause blood vessel relaxation. We
      therefore propose to test the hypothesis that DPP4 inhibition simultaneously enhances GH
      secretion while improving blood glucoses and vascular function in patient populations with
      low GH and increased cardiovascular risk. These preliminary aims serve primarily as a novel
      "proof of concept" study to define the effect of acute pharmacologic DPPIV inhibition on
      stimulated GH secretion.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: Double (Participant, Investigator)
measure: Aim 1: Stimulated Peak Growth Hormone Level
time frame: Growth Hormone Level at 30 minutes (i.e. at completion of arginine infusion), 45 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes
description: Subjects underwent two study days separated by a washout period. On one study day they will receive sitagliptin and on another placebo, in a randomized double-blind fashion. Growth hormone secretion was stimulated using arginine (30 grams i.v. over 30 minutes) on each study day. Growth hormone levels were assessed during a 3 hour period following arginine stimulation.
measure: Aim 1: Percent Change From Baseline in Forearm Vascular Resistance
time frame: Percent change from baseline in forearm vascular resistance at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes
description: Forearm blood flow was determined by strain gauge plethysmography. Forearm vascular resistance was then calculated by dividing this into mean arterial pressure. The percent change from baseline was determined at each timepoint.
measure: Aim 1: Percent Change From Baseline in Forearm Blood Flow
time frame: Percent change from baseline in forearm blood flow at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes.
description: Forearm blood flow was determined by strain gauge plethysmography. The percent change from baseline was determined at each timepoint.
measure: Aim 2: Percent Change From Baseline in Forearm Blood Flow
time frame: Percent change from baseline in forearm blood flow at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes.
description: Subjects undergo two study days separated by a washout period. On one study day they received sitagliptin plus another study drug and on another sitagliptin plus placebo, in a randomized double-blind fashion. Forearm blood flow was assessed at each visit.
measure: Aim 2: Percent Change From Baseline in Forearm Vascular Resistance
time frame: Percent change from baseline in forearm vascular resistance at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes
description: Subjects undergo two study days separated by a washout period. On one study day they will receive sitagliptin plus another study drug and on another sitagliptin plus placebo, in a randomized double-blind fashion. Forearm blood flow was assessed at each visit every 30 minutes for 3 hours. This was divided into mean arterial pressure to determine forearm vascular resistance.
measure: Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels
time frame: baseline and every 30 minutes for 180 minutes
description: In Aim 1 subjects underwent two study days separated by a washout period. On one study day they received study drug and on another placebo, in a randomized double-blind fashion. Venous blood samples were obtained at each visit.
measure: Aim 2: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels
time frame: baseline and every 30 minutes until 180 minutes
description: Subjects undergo two study days separated by a washout period. On one study day they received sitagliptin plus pegvisomant and on another sitagliptin plus placebo, in a randomized double-blind fashion. Tissue plasminogen activator activity (tPA) was assessed at each visit.
measure: Aim 2: Measurement of Growth Hormone (GH) Levels
time frame: baseline and every 30 minutes until 180 minutes
description: Subjects undergo two study days separated by a washout period. On one study day they received sitagliptin plus pegvisomant and on another sitagliptin plus placebo, in a randomized double-blind fashion. Growth hormone secretion following arginine stimulation was assessed at each visit. Growth hormone levels were determined using an assay that is not subject to interference by pegvisomant.
arm group label: Group A (14 healthy subjects)
arm group type: Other
description: In Aim 1: Healthy Lean adults are randomized in a double-blinded cross over fashion to sitagliptin versus placebo.
In Aim 2: Healthy Lean adults receive sitagliptin and are randomized in a double-blinded cross over fashion to pre-treatment with either LNMMA (L-N-Monomethyl-arginine) versus placebo.
arm group label: Group B (14 healthy subjects)
arm group type: Other
description: In Aim 1: Healthy Lean adults are randomized in a double-blinded cross over fashion to sitagliptin versus placebo.
In Aim 2: Healthy Lean adults receive sitagliptin and are randomized in a double-blinded cross over fashion to pre-treatment with either pegvisomant versus placebo.
arm group label: Group C (14 healthy subjects)
arm group type: Other
description: In Aim 1: Healthy Lean adults are randomized in a double-blinded cross over fashion to sitagliptin versus placebo.
In Aim 2: Healthy Lean adults receive sitagliptin and are randomized in a double-blinded cross over fashion to pre-treatment with either Exendin 9-39 versus placebo.
intervention type: Drug
intervention name: Sitagliptin
description: During Aim 1, given on one of two study days (other study day subjects receive placebo.) During Aim 2, given during both of two study days.
arm group label: Group A (14 healthy subjects)
arm group label: Group B (14 healthy subjects)
arm group label: Group C (14 healthy subjects)
other name: Januvia
intervention type: Drug
intervention name: Pegvisomant
description: During Aim 2, given 72 hours prior to one of two study days (Group B subjects only)
arm group label: Group B (14 healthy subjects)
other name: Somavert
intervention type: Drug
intervention name: Placebo
description: During Aim 1, given on one of two study days (other study day subjects receive sitagliptin.) During Aim 2, given on one of two study days (other study day subjects receive either L-NMMA, pegvisomant, or Exendin 9-39 pending their group assignment)
arm group label: Group A (14 healthy subjects)
arm group label: Group B (14 healthy subjects)
arm group label: Group C (14 healthy subjects)
other name: sugar pill
intervention type: Drug
intervention name: L-NMMA
description: During Aim 2, given during one of two study days (Group A subjects only)
arm group label: Group A (14 healthy subjects)
other name: L-N-Monomethyl-arginine
intervention type: Drug
intervention name: Exendin 9-39
description: During Aim 2, given during one of two study days (Group C subjects only)
arm group label: Group C (14 healthy subjects)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jessica K Devin, MD, MSCI
role: Principal Investigator
affiliation: Vanderbilt University Medical Center
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Vanderbilt University
investigator full name: Jessica Koch Devin
investigator title: Assistant Professor
mesh term: Obesity
mesh term: Sitagliptin Phosphate
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 