<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/NCT03012386</url>
  </required_header>
  <id_info>
    <org_study_id>160955</org_study_id>
    <nct_id>NCT03012386</nct_id>
  </id_info>
  <brief_title>CD36 in Nutrient Delivery and Its Dysfunction</brief_title>
  <official_title>Role of CD36 in Nutrient Delivery and Its Dysfunction in African Americans</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderbilt University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Vanderbilt University Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This proposal will test the hypothesis that chronic treatment with sildenafil with and&#xD;
      without the use of nitric oxide substrate, L-arginine, protects against fatty acid induced&#xD;
      impairment of endothelial function, improves insulin-stimulated microvascular recruitment,&#xD;
      insulin sensitivity and glucose uptake in CD36 rs3211938 G-allele carriers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Subjects carrying the G-allele of CD36 coding SNP rs3211938 that results in 50% reduction of&#xD;
      CD36 levels in ~25% of African Americans have endothelial dysfunction. Endothelial&#xD;
      dysfunction results in impairment of insulin's vascular actions and eventually reduced&#xD;
      insulin sensitivity. Insulin induces microvascular recruitment via stimulation of nitric&#xD;
      oxide(NO)-cGMP pathway, which facilitates nutrient flux, e.g., glucose to skeletal muscle.&#xD;
      Elevated fatty acids impair insulin-stimulated microvascular recruitment and reduce insulin&#xD;
      sensitivity. Chronic treatment with sildenafil increases vascularity and muscle glucose&#xD;
      uptake in high fat fed mice. In humans, Drs. Shibao (PI) recently reported that a 3-month&#xD;
      treatment with sildenafil improves insulin sensitivity in patients with impaired glucose&#xD;
      tolerance. More relevant to this project, endothelial dysfunction improved after 4-week&#xD;
      treatment with sildenafil in G-allele carriers. This proposal will test the hypothesis that&#xD;
      chronic treatment with sildenafil with and without the use of NO substrate, L-arginine,&#xD;
      protects against fatty acids induced impairment of endothelial function, improves&#xD;
      insulin-stimulated microvascular.&#xD;
&#xD;
      The protocol design was changed to single arm design.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2017</start_date>
  <completion_date type="Actual">July 31, 2021</completion_date>
  <primary_completion_date type="Actual">July 2021</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Microvascular Blood Volume (MBV) During Insulin Infusion</measure>
    <time_frame>Baseline to end of procedure (approximately 180 minutes)</time_frame>
    <description>Insulin induces microvascular recruitment. Changes in MBV during Insulin infusion signifies insulin sensitivity.&#xD;
MBV is measured in the forearm brachioradialis muscle with contrast enhanced ultrasonography during minutes 120-150 of a hyperinsulinaemic euglycaemic (HIE) clamp (insulin infusion rate up to 80 mU/m2.min-1 ). In the last 30 minutes, L-arginine was infused (10 mg/kg/min for 30 minutes) and ultrasound measurements were repeated upon infusion completion (approximately minute 180).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Microvascular Blood Volume (MBV) During Insulin Infusion After 4 Weeks of Sildenafil Treatment in Both Groups</measure>
    <time_frame>Baseline to 4 weeks</time_frame>
    <description>Chronic treatment with sildenafil increases vascularity and muscle glucose uptake. Changes in MBV during Insulin infusion signifies insulin sensitivity .&#xD;
Insulin sensitivity was tested after 4 weeks of treatment with Sildenafil in both groups. Subjects receive IV infusion of 20% Intralipid (45ml/h) and heparin (200 units/hr). MBV is measured in the forearm brachioradialis muscle with contrast enhanced ultrasonography during minutes 120-150 of a HIE clamp (insulin infusion rate up to 80 mU/m2.min-1 ) In the last 30 minutes, L-arginine was infused (10 mg/kg/min for 30 minutes) and ultrasound measurements were repeated upon infusion completion (approximately minute 180).</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Insulin Resistance</condition>
  <condition>Endothelial Dysfunction</condition>
  <arm_group>
    <arm_group_label>Sildenafil citrate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sildenafil citrate 20 mg three times a day</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sildenafil Citrate in G allele carrier</intervention_name>
    <description>chronic use of phosphodiesterase 5 inhibitor in G allele carrier</description>
    <arm_group_label>Sildenafil citrate</arm_group_label>
    <other_name>viagra, revatio,</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sildenafil Citrate in non G allele carrier</intervention_name>
    <description>chronic use of phosphodiesterase 5 inhibitor in Non G allele carrier</description>
    <arm_group_label>Sildenafil citrate</arm_group_label>
    <other_name>viagra, revatio</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
          -  African American men and women.&#xD;
&#xD;
          -  Age 18-50 years&#xD;
&#xD;
          -  BMI 25-40 kg/m2&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Diabetes type 1 or type 2, as defined by a FPG &gt; 126 mg/dL a two-hour plasma glucose &gt;&#xD;
             200 mg/dL, or the use of anti-diabetic medication&#xD;
&#xD;
          -  Pulmonary hypertension&#xD;
&#xD;
          -  Use of a PDE5 inhibitor for erectile dysfunction&#xD;
&#xD;
          -  Pregnancy or breast-feeding. Women of child-bearing potential will be required to have&#xD;
             undergone tubal ligation or to be using an oral contraceptive or barrier methods of&#xD;
             birth control.&#xD;
&#xD;
          -  Cardiovascular disease such as myocardial infarction, presence of angina pectoris,&#xD;
             significant arrhythmia, congestive heart failure (left ventricular hypertrophy&#xD;
             acceptable), deep vein thrombosis, pulmonary embolism, second or third degree heart&#xD;
             block, mitral valve stenosis, aortic stenosis or hypertrophic cardiomyopathy&#xD;
&#xD;
          -  History of serious neurologic disease such as cerebral hemorrhage, stroke, or&#xD;
             transient ischemic attack&#xD;
&#xD;
          -  History or presence of immunological or hematological disorders&#xD;
&#xD;
          -  Any underlying or acute disease requiring regular medication which could possibly pose&#xD;
             a threat to the subject or make implementation of the protocol or interpretation of&#xD;
             the study results difficult&#xD;
&#xD;
          -  Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days&#xD;
             in 1 month)&#xD;
&#xD;
          -  History of alcohol or drug abuse&#xD;
&#xD;
          -  Mental conditions rendering a subject unable to understand the nature, scope and&#xD;
             possible consequences of the study&#xD;
&#xD;
          -  Inability to comply with the protocol, e.g., uncooperative attitude, inability to&#xD;
             return for follow-up visits, unlikelihood of completing the study, and investigator&#xD;
             discretion&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Cyndya Shibao, MD</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>November 2022</verification_date>
  <study_first_submitted>January 3, 2017</study_first_submitted>
  <study_first_submitted_qc>January 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 6, 2017</study_first_posted>
  <results_first_submitted>May 19, 2022</results_first_submitted>
  <results_first_submitted_qc>November 6, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">November 30, 2022</results_first_posted>
  <last_update_submitted>November 6, 2022</last_update_submitted>
  <last_update_submitted_qc>November 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 30, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Vanderbilt University Medical Center</investigator_affiliation>
    <investigator_full_name>Cyndya Shibao, MD</investigator_full_name>
    <investigator_title>Assistant Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>CD36</keyword>
  <keyword>Endothelial dysfunction</keyword>
  <keyword>African Americans</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin Resistance</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sildenafil Citrate</mesh_term>
    <mesh_term>Citric Acid</mesh_term>
    <mesh_term>Sodium Citrate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 28, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/86/NCT03012386/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>35 subjects were screened, 9 were excluded for not meeting the inclusion criteria</recruitment_details>
      <pre_assignment_details>21 subjects completed the study</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Sildenafil Citrate in G Allele Carriers</title>
          <description>Sildenafil citrate 20 mg three times a day&#xD;
Sildenafil Citrate: phosphodiesterase 5 inhibitor</description>
        </group>
        <group group_id="P2">
          <title>Sildenafil Citrate in Non Carriers of G Allele</title>
          <description>Sildenafil citrate 20 mg three times a day&#xD;
Sildenafil Citrate: phosphodiesterase 5 inhibitor</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Sildenafil Citrate in G Allele Carriers</title>
          <description>Sildenafil citrate 20 mg three times a day&#xD;
Sildenafil Citrate: phosphodiesterase 5 inhibitor</description>
        </group>
        <group group_id="B2">
          <title>Sildenafil Citrate in Non Carriers of G Allele</title>
          <description>Sildenafil citrate 20 mg three times a day&#xD;
Sildenafil Citrate: phosphodiesterase 5 inhibitor</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="8"/>
            <count group_id="B2" value="18"/>
            <count group_id="B3" value="26"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <title>Age</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="42" spread="7.4"/>
                    <measurement group_id="B2" value="33.66" spread="7.4"/>
                    <measurement group_id="B3" value="37.83" spread="7.4"/>
                  </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>
              <title>Gender</title>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="17"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height</title>
          <units>centimeters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="169" spread="9.3"/>
                    <measurement group_id="B2" value="166.22" spread="8.72"/>
                    <measurement group_id="B3" value="167.61" spread="9.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <units>Kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="79" spread="8.34"/>
                    <measurement group_id="B2" value="92.95" spread="14.8"/>
                    <measurement group_id="B3" value="85.9" spread="14.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27.7" spread="2.8"/>
                    <measurement group_id="B2" value="33.53" spread="3.9"/>
                    <measurement group_id="B3" value="30.615" spread="3.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Glucose</title>
          <units>mg/dl</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="81" spread="10.0"/>
                    <measurement group_id="B2" value="83.5" spread="17.7"/>
                    <measurement group_id="B3" value="82.25" spread="17.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Total cholesterol</title>
          <units>mg/dl</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="180" spread="37.1"/>
                    <measurement group_id="B2" value="171.66" spread="29.48"/>
                    <measurement group_id="B3" value="175.83" spread="33.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>HDL</title>
          <units>mg/dl</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="51" spread="13.8"/>
                    <measurement group_id="B2" value="53.38" spread="13.3"/>
                    <measurement group_id="B3" value="52.1" spread="13.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>LDL</title>
          <units>mg/dl</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="106" spread="36.2"/>
                    <measurement group_id="B2" value="100.88" spread="28.25"/>
                    <measurement group_id="B3" value="103.44" spread="32.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Triglycerides</title>
          <units>mg/dl</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="116.37" spread="73.85"/>
                    <measurement group_id="B2" value="87.11" spread="47.42"/>
                    <measurement group_id="B3" value="101.74" spread="60.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Microvascular Blood Volume (MBV) During Insulin Infusion</title>
        <description>Insulin induces microvascular recruitment. Changes in MBV during Insulin infusion signifies insulin sensitivity.&#xD;
MBV is measured in the forearm brachioradialis muscle with contrast enhanced ultrasonography during minutes 120-150 of a hyperinsulinaemic euglycaemic (HIE) clamp (insulin infusion rate up to 80 mU/m2.min-1 ). In the last 30 minutes, L-arginine was infused (10 mg/kg/min for 30 minutes) and ultrasound measurements were repeated upon infusion completion (approximately minute 180).</description>
        <time_frame>Baseline to end of procedure (approximately 180 minutes)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>G Allele Carriers</title>
            <description>The participants were divided into two groups based on the CD36 rs3211938 genotype.&#xD;
subjects carrying the G-allele of CD36 coding SNP rs3211938 that results in reduction of CD36 levels</description>
          </group>
          <group group_id="O2">
            <title>Non Carriers of G Allele</title>
            <description>The participants were divided into two groups based on the CD36 rs3211938 genotype.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Microvascular Blood Volume (MBV) During Insulin Infusion</title>
          <description>Insulin induces microvascular recruitment. Changes in MBV during Insulin infusion signifies insulin sensitivity.&#xD;
MBV is measured in the forearm brachioradialis muscle with contrast enhanced ultrasonography during minutes 120-150 of a hyperinsulinaemic euglycaemic (HIE) clamp (insulin infusion rate up to 80 mU/m2.min-1 ). In the last 30 minutes, L-arginine was infused (10 mg/kg/min for 30 minutes) and ultrasound measurements were repeated upon infusion completion (approximately minute 180).</description>
          <units>ml/kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.16" spread="3.369"/>
                    <measurement group_id="O2" value="11.3" spread="1.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Microvascular Blood Volume (MBV) During Insulin Infusion After 4 Weeks of Sildenafil Treatment in Both Groups</title>
        <description>Chronic treatment with sildenafil increases vascularity and muscle glucose uptake. Changes in MBV during Insulin infusion signifies insulin sensitivity .&#xD;
Insulin sensitivity was tested after 4 weeks of treatment with Sildenafil in both groups. Subjects receive IV infusion of 20% Intralipid (45ml/h) and heparin (200 units/hr). MBV is measured in the forearm brachioradialis muscle with contrast enhanced ultrasonography during minutes 120-150 of a HIE clamp (insulin infusion rate up to 80 mU/m2.min-1 ) In the last 30 minutes, L-arginine was infused (10 mg/kg/min for 30 minutes) and ultrasound measurements were repeated upon infusion completion (approximately minute 180).</description>
        <time_frame>Baseline to 4 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sildenafil Citrate in G Allele Carriers</title>
            <description>Chronic use of phosphodiesterase 5 inhibitor in G allele carrier&#xD;
Other names: Viagra, Revatio&#xD;
Sildenafil citrate 20 mg three times a day for 4 weeks</description>
          </group>
          <group group_id="O2">
            <title>Sildenafil Citrate in Non Carriers of G Allele</title>
            <description>Chronic use of phosphodiesterase 5 inhibitor in Non carriers of G allele&#xD;
Other names: Viagra, Revatio&#xD;
Sildenafil citrate 20 mg three times a day for 4 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Microvascular Blood Volume (MBV) During Insulin Infusion After 4 Weeks of Sildenafil Treatment in Both Groups</title>
          <description>Chronic treatment with sildenafil increases vascularity and muscle glucose uptake. Changes in MBV during Insulin infusion signifies insulin sensitivity .&#xD;
Insulin sensitivity was tested after 4 weeks of treatment with Sildenafil in both groups. Subjects receive IV infusion of 20% Intralipid (45ml/h) and heparin (200 units/hr). MBV is measured in the forearm brachioradialis muscle with contrast enhanced ultrasonography during minutes 120-150 of a HIE clamp (insulin infusion rate up to 80 mU/m2.min-1 ) In the last 30 minutes, L-arginine was infused (10 mg/kg/min for 30 minutes) and ultrasound measurements were repeated upon infusion completion (approximately minute 180).</description>
          <units>ml/kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.93" spread="2.31"/>
                    <measurement group_id="O2" value="8.4" spread="0.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>12 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Sildenafil Citrate</title>
          <description>Sildenafil citrate 20 mg three times a day&#xD;
Sildenafil Citrate in G allele carrier: chronic use of phosphodiesterase 5 inhibitor in G allele carrier&#xD;
Sildenafil Citrate in non G allele carrier: chronic use of phosphodiesterase 5 inhibitor in Non G allele carrier</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <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="26"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Malaria</sub_title>
                <description>non drug related event</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Pregnancy, puerperium and perinatal conditions</title>
            <event_list>
              <event>
                <sub_title>Positive pregnancy test</sub_title>
                <description>Volunteer was terminated from the study due to positive and urine pregnancy tests</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <description>Diarrhea frst 5 days of taking study medication</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upset stomach / stomach virus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Low back pain/ Leg heaviness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headaches</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Burst of enerygy/ Irritability</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough congestion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash and itchiness all over the body</sub_title>
                <description>Rash and pruritis was drug related. Subject responded to Hydroxyzine. No shortness of breath , no swelling and no wheezing was noted during the entire episode</description>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="26"/>
              </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>Cyndya Shibao MD</name_or_title>
      <organization>Vanderbilt University Medical Center</organization>
      <phone>6159364584</phone>
      <email>cyndya.shibao@vumc.org</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/NCT03012386
org study id: 160955
nct id: NCT03012386
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This proposal will test the hypothesis that chronic treatment with sildenafil with and
      without the use of nitric oxide substrate, L-arginine, protects against fatty acid induced
      impairment of endothelial function, improves insulin-stimulated microvascular recruitment,
      insulin sensitivity and glucose uptake in CD36 rs3211938 G-allele carriers.
Subjects carrying the G-allele of CD36 coding SNP rs3211938 that results in 50% reduction of
      CD36 levels in ~25% of African Americans have endothelial dysfunction. Endothelial
      dysfunction results in impairment of insulin's vascular actions and eventually reduced
      insulin sensitivity. Insulin induces microvascular recruitment via stimulation of nitric
      oxide(NO)-cGMP pathway, which facilitates nutrient flux, e.g., glucose to skeletal muscle.
      Elevated fatty acids impair insulin-stimulated microvascular recruitment and reduce insulin
      sensitivity. Chronic treatment with sildenafil increases vascularity and muscle glucose
      uptake in high fat fed mice. In humans, Drs. Shibao (PI) recently reported that a 3-month
      treatment with sildenafil improves insulin sensitivity in patients with impaired glucose
      tolerance. More relevant to this project, endothelial dysfunction improved after 4-week
      treatment with sildenafil in G-allele carriers. This proposal will test the hypothesis that
      chronic treatment with sildenafil with and without the use of NO substrate, L-arginine,
      protects against fatty acids induced impairment of endothelial function, improves
      insulin-stimulated microvascular.

      The protocol design was changed to single arm design.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Change in Microvascular Blood Volume (MBV) During Insulin Infusion
time frame: Baseline to end of procedure (approximately 180 minutes)
description: Insulin induces microvascular recruitment. Changes in MBV during Insulin infusion signifies insulin sensitivity.
MBV is measured in the forearm brachioradialis muscle with contrast enhanced ultrasonography during minutes 120-150 of a hyperinsulinaemic euglycaemic (HIE) clamp (insulin infusion rate up to 80 mU/m2.min-1 ). In the last 30 minutes, L-arginine was infused (10 mg/kg/min for 30 minutes) and ultrasound measurements were repeated upon infusion completion (approximately minute 180).
measure: Change in Microvascular Blood Volume (MBV) During Insulin Infusion After 4 Weeks of Sildenafil Treatment in Both Groups
time frame: Baseline to 4 weeks
description: Chronic treatment with sildenafil increases vascularity and muscle glucose uptake. Changes in MBV during Insulin infusion signifies insulin sensitivity .
Insulin sensitivity was tested after 4 weeks of treatment with Sildenafil in both groups. Subjects receive IV infusion of 20% Intralipid (45ml/h) and heparin (200 units/hr). MBV is measured in the forearm brachioradialis muscle with contrast enhanced ultrasonography during minutes 120-150 of a HIE clamp (insulin infusion rate up to 80 mU/m2.min-1 ) In the last 30 minutes, L-arginine was infused (10 mg/kg/min for 30 minutes) and ultrasound measurements were repeated upon infusion completion (approximately minute 180).
arm group label: Sildenafil citrate
arm group type: Experimental
description: Sildenafil citrate 20 mg three times a day
intervention type: Drug
intervention name: Sildenafil Citrate in G allele carrier
description: chronic use of phosphodiesterase 5 inhibitor in G allele carrier
arm group label: Sildenafil citrate
other name: viagra, revatio,
intervention type: Drug
intervention name: Sildenafil Citrate in non G allele carrier
description: chronic use of phosphodiesterase 5 inhibitor in Non G allele carrier
arm group label: Sildenafil citrate
other name: viagra, revatio
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Cyndya Shibao, MD
role: Principal Investigator
affiliation: Vanderbilt University Medical Center
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Vanderbilt University Medical Center
investigator full name: Cyndya Shibao, MD
investigator title: Assistant Professor of Medicine
mesh term: Insulin Resistance
mesh term: Sildenafil Citrate
mesh term: Citric Acid
mesh term: Sodium Citrate
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 