<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/NCT01684748</url>
  </required_header>
  <id_info>
    <org_study_id>arbfat</org_study_id>
    <nct_id>NCT01684748</nct_id>
  </id_info>
  <brief_title>Angiotensin II Blockade and Inflammation in Obesity</brief_title>
  <acronym>ARB</acronym>
  <official_title>Angiotensin II Blockade and Adipose Tissue Inflammation in Obesity</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Virginia Polytechnic Institute and State University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Virginia Polytechnic Institute and State University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Overweight and obesity, which afflicts ~65% of the U.S. population and more than 1 billion&#xD;
      people worldwide, increases the risk of developing hypertension. Activation of the renin&#xD;
      angiotensin system (RAS) is an important mechanism by which obesity leads to hypertension. In&#xD;
      addition to its vasoconstricting and sodium retaining actions, angiotensin II also has potent&#xD;
      pro-inflammatory actions including macrophage infiltration and expression of proinflammatory&#xD;
      cytokines in target tissues. Adipose tissue and skeletal muscle appear to be a key sites for&#xD;
      the generation of proinflammatory cytokines. Although angiotensin II receptor blockade&#xD;
      reduces inflammation in many tissues, the effects on adipose tissue and skeletal muscle in&#xD;
      humans are not clear. Importantly, the chronic low grade inflammatory state that accompanies&#xD;
      obesity complicates hypertension by contributing to insulin resistance and accelerating&#xD;
      cardiovascular disease. Therefore, the general aim of the present proposal will be to&#xD;
      determine the influence of angiotensin II receptor blockade on adipose tissue and skeletal&#xD;
      muscle inflammation and its relation to improvements in insulin sensitivity, if observed, in&#xD;
      obese hypertensive humans. To address these aims, 44 obese (BMI&gt;30 kg/m2) hypertensive&#xD;
      (BP&gt;140 systolic and/or 90 diastolic) individuals (age=50-65 years) will be randomized to&#xD;
      receive 8 weeks of either the angiotensin II receptor antagonist, olmesartan medoxomil, or no&#xD;
      treatment in a crossover manner. Subcutaneous adipose tissue and skeletal muscle biopsies&#xD;
      will be obtained and insulin sensitivity (intravenous glucose tolerance tests) will be&#xD;
      assessed at baseline and following 8 weeks of each intervention. A two week washout period&#xD;
      will separate the interventions.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>February 2009</start_date>
  <completion_date type="Actual">August 2011</completion_date>
  <primary_completion_date type="Actual">August 2011</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>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Insulin Sensitivity by Intravenous Glucose Tolerance Testing (Change Over Time)</measure>
    <time_frame>Baseline testing to post-testing after 8-week intervention</time_frame>
    <description>Data collected from the intravenous glucose tolerance tests included blood concentrations of glucose and insulin. Glucose was measured immediately on a YSI glucose analyzer and insulin was measured via ELISA colormetric kits once all study samples were collected. To analyze changes in insulin sensitivity, the MINMOD software was used. The MINMOD software uses Bergman's minimal model to determine insulin sensitivity during an intravenous glucose tolerance test. Both glucose and insulin values were inserted at each timepoint collected (33 in total over the 3-hour protocol) and the software was run to generate the insulin sensitivity value at baseline and post-test. This information was then used to calculate the change of insulin sensitivity from baseline to post-testing after each 8-week intervention.</description>
  </primary_outcome>
  <other_outcome>
    <measure>Collagen Gene Expression in Skeletal Muscle (Change Over Time)</measure>
    <time_frame>Baseline testing to post-testing after 8-week intervention</time_frame>
    <description>RNA extraction and quantification were determined using an RNeasy Mini Fibrous Kit and DNase I treatment (Qiagen, Valencia, CA, USA) in accordance to the manufacturer's directions for mRNA extraction. Quantitative real-time polymerase chain reaction (qRT-PCR) measured the expression of collagen III using an ABI PRISM 7900 Sequence Detection System instrument and TaqMan Universal PCR Master Mix according to the manufacturer's instructions (Applied Biosystems, Foster City, CA, USA). Relative gene expression levels were determined using the number of cycles necessary to reach threshold and results were normalized to cyclophilin B RNA levels.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Overweight</condition>
  <condition>Obese</condition>
  <condition>Prehypertension</condition>
  <condition>Hypertension</condition>
  <arm_group>
    <arm_group_label>Olmesartan Medoxomil first, then No Drug</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>During the First Intervention (8 weeks), subjects will be provided with daily 20 mg of olmesartan for the first 2 weeks. Subjects receive additional daily doses of 40 mg olmesartan for the remainder of the study period (6 weeks). The dose remains at 20 mg per day, however, if BP falls below 110/70 during the first 2 weeks. In addition, subjects will continue taking the drug during the 2-week follow-up testing period. Subjects will then proceed to the Washout period (2 weeks). During the Second Intervention (8 weeks), no drug will be administered to the subjects.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No Drug first, then Olmesartan Medoxomil</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>During the First Intervention (8 weeks), no drug will be administered to the subjects. Subjects will then proceed to the Washout period (2 weeks). During the Second Intervention (8 weeks), subjects will be provided with daily 20 mg of olmesartan for the first 2 weeks. Subjects then receive daily doses of 40 mg olmesartan for the remainder of the study period (6 weeks). The dose remains at 20 mg per day, however, if BP falls below 110/70 during the first 2 weeks. In addition, subjects will continue taking the drug during the 2-week follow-up testing period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Olmesartan medoxomil</intervention_name>
    <description>Crossover intervention comparing antihypertensive medication to no drug intervention.</description>
    <arm_group_label>No Drug first, then Olmesartan Medoxomil</arm_group_label>
    <arm_group_label>Olmesartan Medoxomil first, then No Drug</arm_group_label>
    <other_name>Benicar</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18-75 years of age&#xD;
&#xD;
          -  Weight stable for previous 6 months (+2.0kg)&#xD;
&#xD;
          -  Sedentary to recreationally active&#xD;
&#xD;
          -  Willing to be randomized to treatment or placebo&#xD;
&#xD;
          -  Verbal and written informed consent&#xD;
&#xD;
          -  Approved for participation by Medical Director (Jose Rivero, M.D.)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Blood pressure outside stated range&#xD;
&#xD;
          -  Diabetes or taking diabetes medications&#xD;
&#xD;
          -  Total cholesterol &gt;6.2 mmol/L; triglycerides &gt;4.5 mmol/L&#xD;
&#xD;
          -  Past or current ischemic heart disease, stroke, respiratory disease, endocrine or&#xD;
             metabolic disease, neurological disease, or hematological-oncological disease&#xD;
&#xD;
          -  Evidence of renal insufficiency; GFR&lt; 60 ml/min*&#xD;
&#xD;
          -  Medications (including but not limited to antihypertensives, statins or other with&#xD;
             anti-inflammatory actions) or antioxidant vitamins or supplements&#xD;
&#xD;
          -  Known allergy or hypersensitivity to olmesartan or any of its components&#xD;
&#xD;
          -  Pregnant or planning to become pregnant&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kevin P. Davy, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Virginia Polytechnic Institute and State University</affiliation>
  </overall_official>
  <verification_date>December 2017</verification_date>
  <study_first_submitted>September 6, 2012</study_first_submitted>
  <study_first_submitted_qc>September 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 13, 2012</study_first_posted>
  <results_first_submitted>May 29, 2014</results_first_submitted>
  <results_first_submitted_qc>January 8, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">January 12, 2015</results_first_posted>
  <last_update_submitted>December 6, 2017</last_update_submitted>
  <last_update_submitted_qc>December 6, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">January 3, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Virginia Polytechnic Institute and State University</investigator_affiliation>
    <investigator_full_name>Kevin Davy</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>angiotensin II</keyword>
  <keyword>obesity</keyword>
  <keyword>diabetes</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prehypertension</mesh_term>
    <mesh_term>Obesity</mesh_term>
    <mesh_term>Overweight</mesh_term>
    <mesh_term>Inflammation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Olmesartan</mesh_term>
    <mesh_term>Olmesartan Medoxomil</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Olmesartan Medoxomil First, Then No Drug</title>
          <description>During the First Intervention (8 weeks), subjects will be provided with daily 20 mg of olmesartan for the first 2 weeks. Subjects receive additional daily doses of 40 mg olmesartan for the remainder of the study period (6 weeks). The dose remains at 20 mg per day, however, if BP falls below 110/70 during the first 2 weeks. In addition, subjects will continue taking the drug during the 2-week follow-up testing period. Subjects will then proceed to the Washout period (2 weeks). During the Second Intervention (8 weeks), no drug will be administered to the subjects.&#xD;
Olmesartan medoxomil</description>
        </group>
        <group group_id="P2">
          <title>No Drug First, Then Olmesartan Medoxomil</title>
          <description>During the First Intervention (8 weeks), no drug will be administered to the subjects. Subjects will then proceed to the Washout period (2 weeks). During the Second Intervention (8 weeks), subjects will be provided with daily 20 mg of olmesartan for the first 2 weeks. Subjects then receive daily doses of 40 mg olmesartan for the remainder of the study period (6 weeks). The dose remains at 20 mg per day, however, if BP falls below 110/70 during the first 2 weeks. In addition, subjects will continue taking the drug during the 2-week follow-up testing period.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>First Intervention - 8 Weeks</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Second Intervention - 8 Weeks</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Olmesartan Medoxomil First, Then No Drug</title>
          <description>During the First Intervention (8 weeks), subjects will be provided with daily 20 mg of olmesartan for the first 2 weeks. Subjects receive additional daily doses of 40 mg olmesartan for the remainder of the study period (6 weeks). The dose remains at 20 mg per day, however, if BP falls below 110/70 during the first 2 weeks. In addition, subjects will continue taking the drug during the 2-week follow-up testing period. Subjects will then proceed to the Washout period (2 weeks). During the Second Intervention (8 weeks), no drug will be administered to the subjects.&#xD;
Olmesartan medoxomil</description>
        </group>
        <group group_id="B2">
          <title>No Drug First, Then Olmesartan Medoxomil</title>
          <description>During the First Intervention (8 weeks), no drug will be administered to the subjects. Subjects will then proceed to the Washout period (2 weeks). During the Second Intervention (8 weeks), subjects will be provided with daily 20 mg of olmesartan for the first 2 weeks. Subjects then receive daily doses of 40 mg olmesartan for the remainder of the study period (6 weeks). The dose remains at 20 mg per day, however, if BP falls below 110/70 during the first 2 weeks. In addition, subjects will continue taking the drug during the 2-week follow-up testing period.</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="8"/>
            <count group_id="B3" value="16"/>
          </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="49.25" spread="9.8"/>
                    <measurement group_id="B2" value="49.75" spread="14.2"/>
                    <measurement group_id="B3" value="49.5" spread="11.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </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="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="8"/>
                  </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="8"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body 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="102.3" spread="20.9"/>
                    <measurement group_id="B2" value="90.4" spread="17.7"/>
                    <measurement group_id="B3" value="96.3" spread="19.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body mass index</title>
          <units>kg/m2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="34.5" spread="7.0"/>
                    <measurement group_id="B2" value="31.5" spread="6.8"/>
                    <measurement group_id="B3" value="33.0" spread="6.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body fat</title>
          <units>Percentage of fat</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="43.9" spread="10.5"/>
                    <measurement group_id="B2" value="39.8" spread="13.5"/>
                    <measurement group_id="B3" value="41.8" spread="12.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Total fat mass</title>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="43.1" spread="15.1"/>
                    <measurement group_id="B2" value="34.6" spread="14.7"/>
                    <measurement group_id="B3" value="38.8" spread="15.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Systolic blood pressure</title>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="133.7" spread="10.1"/>
                    <measurement group_id="B2" value="140.6" spread="12.8"/>
                    <measurement group_id="B3" value="137.2" spread="11.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Diastolic blood pressure</title>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="81.0" spread="5.1"/>
                    <measurement group_id="B2" value="80.1" spread="7.9"/>
                    <measurement group_id="B3" value="80.6" spread="6.4"/>
                  </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="120.6" spread="68.5"/>
                    <measurement group_id="B2" value="106.8" spread="50.9"/>
                    <measurement group_id="B3" value="113.7" spread="53.6"/>
                  </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="199.5" spread="38.2"/>
                    <measurement group_id="B2" value="207.8" spread="20.9"/>
                    <measurement group_id="B3" value="203.7" spread="30.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>HDL 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="45.5" spread="9.8"/>
                    <measurement group_id="B2" value="55.1" spread="29.0"/>
                    <measurement group_id="B3" value="50.3" spread="21.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>LDL 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="129.9" spread="34.9"/>
                    <measurement group_id="B2" value="131.3" spread="22.4"/>
                    <measurement group_id="B3" value="130.6" spread="31.2"/>
                  </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="95.8" spread="10.8"/>
                    <measurement group_id="B2" value="99.1" spread="13.8"/>
                    <measurement group_id="B3" value="97.4" spread="12.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Insulin Sensitivity by Intravenous Glucose Tolerance Testing (Change Over Time)</title>
        <description>Data collected from the intravenous glucose tolerance tests included blood concentrations of glucose and insulin. Glucose was measured immediately on a YSI glucose analyzer and insulin was measured via ELISA colormetric kits once all study samples were collected. To analyze changes in insulin sensitivity, the MINMOD software was used. The MINMOD software uses Bergman's minimal model to determine insulin sensitivity during an intravenous glucose tolerance test. Both glucose and insulin values were inserted at each timepoint collected (33 in total over the 3-hour protocol) and the software was run to generate the insulin sensitivity value at baseline and post-test. This information was then used to calculate the change of insulin sensitivity from baseline to post-testing after each 8-week intervention.</description>
        <time_frame>Baseline testing to post-testing after 8-week intervention</time_frame>
        <population>Results of insulin sensitivity by intravenous glucose tolerance (IVGTT) testing are reported per intervention (Olmesartan Medoxomil and No drug). Only 10 of the 16 study participants who participated in all or some of the study measurements opted to complete or had sufficient data to analyze for each pre- and post-intervention (4 total) IVGTT.</population>
        <group_list>
          <group group_id="O1">
            <title>Olmesartan Medoxomil</title>
            <description>Subjects will be provided with daily 20 mg of olmesartan for the first 2 weeks during the 8-week intervention. Subjects receive additional daily doses of 40 mg olmesartan for the remainder of the study period. The dose remains at 20 mg per day, however, if BP falls below 110/70 during the first 2 weeks, subjects will continue taking the drug during the 2-week follow-up period.&#xD;
Olmesartan medoxomil</description>
          </group>
          <group group_id="O2">
            <title>No Drug Intervention</title>
            <description>The no-drug intervention (i.e., no placebo is provided) is an 8-week no intervention comparison.</description>
          </group>
        </group_list>
        <measure>
          <title>Insulin Sensitivity by Intravenous Glucose Tolerance Testing (Change Over Time)</title>
          <description>Data collected from the intravenous glucose tolerance tests included blood concentrations of glucose and insulin. Glucose was measured immediately on a YSI glucose analyzer and insulin was measured via ELISA colormetric kits once all study samples were collected. To analyze changes in insulin sensitivity, the MINMOD software was used. The MINMOD software uses Bergman's minimal model to determine insulin sensitivity during an intravenous glucose tolerance test. Both glucose and insulin values were inserted at each timepoint collected (33 in total over the 3-hour protocol) and the software was run to generate the insulin sensitivity value at baseline and post-test. This information was then used to calculate the change of insulin sensitivity from baseline to post-testing after each 8-week intervention.</description>
          <population>Results of insulin sensitivity by intravenous glucose tolerance (IVGTT) testing are reported per intervention (Olmesartan Medoxomil and No drug). Only 10 of the 16 study participants who participated in all or some of the study measurements opted to complete or had sufficient data to analyze for each pre- and post-intervention (4 total) IVGTT.</population>
          <units>mu/L/min</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.253" spread="2.7"/>
                    <measurement group_id="O2" value="-0.804" spread="2.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Collagen Gene Expression in Skeletal Muscle (Change Over Time)</title>
        <description>RNA extraction and quantification were determined using an RNeasy Mini Fibrous Kit and DNase I treatment (Qiagen, Valencia, CA, USA) in accordance to the manufacturer's directions for mRNA extraction. Quantitative real-time polymerase chain reaction (qRT-PCR) measured the expression of collagen III using an ABI PRISM 7900 Sequence Detection System instrument and TaqMan Universal PCR Master Mix according to the manufacturer's instructions (Applied Biosystems, Foster City, CA, USA). Relative gene expression levels were determined using the number of cycles necessary to reach threshold and results were normalized to cyclophilin B RNA levels.</description>
        <time_frame>Baseline testing to post-testing after 8-week intervention</time_frame>
        <population>Results are reported for the Olmesartan Medoxomil intervention only; there was insufficient RNA yield for the majority of participants during the no drug treatment. Only 7 of the 16 study participants who participated in the study measurements had sufficient data to analyze the pre- and post-intervention skeletal muscle biopsy tissues.</population>
        <group_list>
          <group group_id="O1">
            <title>Olmesartan Medoxomil</title>
            <description>Subjects will be provided with daily 20 mg of olmesartan for the first 2 weeks during the 8-week intervention. Subjects receive additional daily doses of 40 mg olmesartan for the remainder of the study period. The dose remains at 20 mg per day, however, if BP falls below 110/70 during the first 2 weeks, subjects will continue taking the drug during the 2-week follow-up period.&#xD;
Olmesartan medoxomil</description>
          </group>
        </group_list>
        <measure>
          <title>Collagen Gene Expression in Skeletal Muscle (Change Over Time)</title>
          <description>RNA extraction and quantification were determined using an RNeasy Mini Fibrous Kit and DNase I treatment (Qiagen, Valencia, CA, USA) in accordance to the manufacturer's directions for mRNA extraction. Quantitative real-time polymerase chain reaction (qRT-PCR) measured the expression of collagen III using an ABI PRISM 7900 Sequence Detection System instrument and TaqMan Universal PCR Master Mix according to the manufacturer's instructions (Applied Biosystems, Foster City, CA, USA). Relative gene expression levels were determined using the number of cycles necessary to reach threshold and results were normalized to cyclophilin B RNA levels.</description>
          <population>Results are reported for the Olmesartan Medoxomil intervention only; there was insufficient RNA yield for the majority of participants during the no drug treatment. Only 7 of the 16 study participants who participated in the study measurements had sufficient data to analyze the pre- and post-intervention skeletal muscle biopsy tissues.</population>
          <units>Arbitrary unit (AU)</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_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pre-Olmesartan medoxomil</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1491" spread="510"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post-Olmesartan medoxomil</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="774" spread="271"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Olmesartan Medoxomil</title>
          <description>Subjects will be provided with daily 20 mg of olmesartan for the first 2 weeks during the 8-week intervention. Subjects receive additional daily doses of 40 mg olmesartan for the remainder of the study period. The dose remains at 20 mg per day, however, if BP falls below 110/70 during the first 2 weeks, subjects will continue taking the drug during the 2-week follow-up period.&#xD;
Olmesartan medoxomil</description>
        </group>
        <group group_id="E2">
          <title>No Drug Intervention</title>
          <description>The no-drug intervention (i.e., no placebo is provided) is an 8-week no intervention comparison.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </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>Elaina Marinik, Ph.D.</name_or_title>
      <organization>Virginia Polytechnic Institute &amp; State University</organization>
      <phone>5402318299</phone>
      <email>emarinik@vt.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/NCT01684748
org study id: arbfat
nct id: NCT01684748
lead sponsor: 
collaborator: 
has dmc: Yes
Overweight and obesity, which afflicts ~65% of the U.S. population and more than 1 billion
      people worldwide, increases the risk of developing hypertension. Activation of the renin
      angiotensin system (RAS) is an important mechanism by which obesity leads to hypertension. In
      addition to its vasoconstricting and sodium retaining actions, angiotensin II also has potent
      pro-inflammatory actions including macrophage infiltration and expression of proinflammatory
      cytokines in target tissues. Adipose tissue and skeletal muscle appear to be a key sites for
      the generation of proinflammatory cytokines. Although angiotensin II receptor blockade
      reduces inflammation in many tissues, the effects on adipose tissue and skeletal muscle in
      humans are not clear. Importantly, the chronic low grade inflammatory state that accompanies
      obesity complicates hypertension by contributing to insulin resistance and accelerating
      cardiovascular disease. Therefore, the general aim of the present proposal will be to
      determine the influence of angiotensin II receptor blockade on adipose tissue and skeletal
      muscle inflammation and its relation to improvements in insulin sensitivity, if observed, in
      obese hypertensive humans. To address these aims, 44 obese (BMI>30 kg/m2) hypertensive
      (BP>140 systolic and/or 90 diastolic) individuals (age=50-65 years) will be randomized to
      receive 8 weeks of either the angiotensin II receptor antagonist, olmesartan medoxomil, or no
      treatment in a crossover manner. Subcutaneous adipose tissue and skeletal muscle biopsies
      will be obtained and insulin sensitivity (intravenous glucose tolerance tests) will be
      assessed at baseline and following 8 weeks of each intervention. A two week washout period
      will separate the interventions.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Insulin Sensitivity by Intravenous Glucose Tolerance Testing (Change Over Time)
time frame: Baseline testing to post-testing after 8-week intervention
description: Data collected from the intravenous glucose tolerance tests included blood concentrations of glucose and insulin. Glucose was measured immediately on a YSI glucose analyzer and insulin was measured via ELISA colormetric kits once all study samples were collected. To analyze changes in insulin sensitivity, the MINMOD software was used. The MINMOD software uses Bergman's minimal model to determine insulin sensitivity during an intravenous glucose tolerance test. Both glucose and insulin values were inserted at each timepoint collected (33 in total over the 3-hour protocol) and the software was run to generate the insulin sensitivity value at baseline and post-test. This information was then used to calculate the change of insulin sensitivity from baseline to post-testing after each 8-week intervention.
measure: Collagen Gene Expression in Skeletal Muscle (Change Over Time)
time frame: Baseline testing to post-testing after 8-week intervention
description: RNA extraction and quantification were determined using an RNeasy Mini Fibrous Kit and DNase I treatment (Qiagen, Valencia, CA, USA) in accordance to the manufacturer's directions for mRNA extraction. Quantitative real-time polymerase chain reaction (qRT-PCR) measured the expression of collagen III using an ABI PRISM 7900 Sequence Detection System instrument and TaqMan Universal PCR Master Mix according to the manufacturer's instructions (Applied Biosystems, Foster City, CA, USA). Relative gene expression levels were determined using the number of cycles necessary to reach threshold and results were normalized to cyclophilin B RNA levels.
arm group label: Olmesartan Medoxomil first, then No Drug
arm group type: Experimental
description: During the First Intervention (8 weeks), subjects will be provided with daily 20 mg of olmesartan for the first 2 weeks. Subjects receive additional daily doses of 40 mg olmesartan for the remainder of the study period (6 weeks). The dose remains at 20 mg per day, however, if BP falls below 110/70 during the first 2 weeks. In addition, subjects will continue taking the drug during the 2-week follow-up testing period. Subjects will then proceed to the Washout period (2 weeks). During the Second Intervention (8 weeks), no drug will be administered to the subjects.
arm group label: No Drug first, then Olmesartan Medoxomil
arm group type: Experimental
description: During the First Intervention (8 weeks), no drug will be administered to the subjects. Subjects will then proceed to the Washout period (2 weeks). During the Second Intervention (8 weeks), subjects will be provided with daily 20 mg of olmesartan for the first 2 weeks. Subjects then receive daily doses of 40 mg olmesartan for the remainder of the study period (6 weeks). The dose remains at 20 mg per day, however, if BP falls below 110/70 during the first 2 weeks. In addition, subjects will continue taking the drug during the 2-week follow-up testing period.
intervention type: Drug
intervention name: Olmesartan medoxomil
description: Crossover intervention comparing antihypertensive medication to no drug intervention.
arm group label: No Drug first, then Olmesartan Medoxomil
arm group label: Olmesartan Medoxomil first, then No Drug
other name: Benicar
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Kevin P. Davy, Ph.D.
role: Principal Investigator
affiliation: Virginia Polytechnic Institute and State University
responsible party type: Principal Investigator
investigator affiliation: Virginia Polytechnic Institute and State University
investigator full name: Kevin Davy
investigator title: Professor
mesh term: Prehypertension
mesh term: Obesity
mesh term: Overweight
mesh term: Inflammation
mesh term: Olmesartan
mesh term: Olmesartan Medoxomil
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 