<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/NCT02236520</url>
  </required_header>
  <id_info>
    <org_study_id>141382</org_study_id>
    <nct_id>NCT02236520</nct_id>
  </id_info>
  <brief_title>Tissue Sodium in Pre-hypertensive Patients</brief_title>
  <official_title>Tissue Sodium in Pre-hypertensive Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderbilt University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>American Heart Association</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Vanderbilt University Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Cardiovascular disease is the first common cause of death worldwide. Hypertension is the&#xD;
      number one driving risk factor. Hypertension has long been associated with dietary salt&#xD;
      intake. We believe that the accumulation of salt in the interstitium and inside cells&#xD;
      represents a neglected risk factor, which initiates a pro-inflammatory state, chronically&#xD;
      increases blood pressure, and leads to systemic energy imbalance. We will explore the concept&#xD;
      that Na+ storage in the skin and in muscle is associated with increased blood pressure, a&#xD;
      pro-inflammatory state, and reduced insulin sensitivity. We will do so by addressing the&#xD;
      following specific aims:&#xD;
&#xD;
        -  Specific Aim 1: To test the hypothesis that African Americans are characterized by&#xD;
           increased tissue Na+ storage, which is paralleled by higher blood pressure, reduced&#xD;
           forearm blood flow, and enhanced pulse wave velocity&#xD;
&#xD;
        -  Specific Aim 2: To test the hypothesis that treatment with spironolactone reduces tissue&#xD;
           Na+ content&#xD;
&#xD;
        -  Specific Aim 3: To test the hypothesis that Na+ storage leads to immune cell activation&#xD;
&#xD;
        -  Specific Aim 4: To test the hypothesis that the accumulation of salt in skin and muscle&#xD;
           is associated with decreased insulin sensitivity and propensity to diabetes mellitus&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2014</start_date>
  <completion_date type="Actual">May 1, 2018</completion_date>
  <primary_completion_date type="Actual">May 1, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Tissue Sodium Concentration Measured Using Sodium Magnetic Resonance Imaging (NaMRI)</measure>
    <time_frame>baseline and 8 weeks</time_frame>
    <description>NaMRI is a sensitive laboratory assessment of the concentration of sodium in tissue</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">71</enrollment>
  <condition>Hypertension</condition>
  <arm_group>
    <arm_group_label>Spironolactone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>50 mg capsule of Spironolactone administered orally 1 per day for 8 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Chlorthalidone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>25 mg capsule of Chlorthalidone administered orally 1 per day for 8 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Diet</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>diet of 6 g salt per day for 8 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>placebo capsule administered orally 1 per day for 8 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Spironolactone</intervention_name>
    <arm_group_label>Spironolactone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Chlorthalidone</intervention_name>
    <arm_group_label>Chlorthalidone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Diet</intervention_name>
    <arm_group_label>Diet</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 30 to 80 years old;&#xD;
&#xD;
          -  Systolic blood pressures between 110 to 150 mmHg and/or diastolic blood pressure&#xD;
             between 80-99 mmHg;&#xD;
&#xD;
          -  Ability to give informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy;&#xD;
&#xD;
          -  Intolerance to study protocols;&#xD;
&#xD;
          -  Acute cardiovascular events within the previous 6 months;&#xD;
&#xD;
          -  Impaired renal function [estimated glomerular filtration rate (GFR) &lt; 45&#xD;
             ml/min/1.73m^2];&#xD;
&#xD;
          -  Current or recent treatment with systemic glucocorticoid therapy (within 1 month of&#xD;
             enrollment);&#xD;
&#xD;
          -  Current use of anti-hypertensive medication (except calcium channel blockers and beta&#xD;
             blockers);&#xD;
&#xD;
          -  Diabetes mellitus requiring medical therapy;&#xD;
&#xD;
          -  Morbid obesity (BMI &gt; 45);&#xD;
&#xD;
          -  Prior adverse reaction to a thiazide or spironolactone;&#xD;
&#xD;
          -  Claustrophobia preventing the patient from having an MRI or other contraindications to&#xD;
             MRI;&#xD;
&#xD;
          -  Impaired hepatic function (aspartate amino transaminase and/or alanine amino&#xD;
             transaminase &gt; 1.5x upper limit of normal range);&#xD;
&#xD;
          -  Current illicit drug use;&#xD;
&#xD;
          -  Sexually active women of childbearing potential** who are unwilling to practice&#xD;
             adequate contraception during the study [adequate contraceptive measures include&#xD;
             stable use of oral contraceptives or other prescription pharmaceutical contraceptives&#xD;
             for 2 or more menstrual cycles prior to screening; intrauterine device (IUD);&#xD;
             bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly,&#xD;
             or diaphragm plus contraceptive sponge, foam, or jelly].&#xD;
&#xD;
               -  Postmenopausal women must be amenorrheic for at least 12 months in order not to&#xD;
                  be considered of child bearing potential. Pregnancy testing and contraception are&#xD;
                  not required for women with documented hysterectomy or tubal ligation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alp Ikizler, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vanderbilt University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jens Titze, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vanderbilt University</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>April 2019</verification_date>
  <study_first_submitted>September 8, 2014</study_first_submitted>
  <study_first_submitted_qc>September 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2014</study_first_posted>
  <results_first_submitted>April 30, 2019</results_first_submitted>
  <results_first_submitted_qc>April 30, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">May 22, 2019</results_first_posted>
  <last_update_submitted>April 30, 2019</last_update_submitted>
  <last_update_submitted_qc>April 30, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 22, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Vanderbilt University Medical Center</investigator_affiliation>
    <investigator_full_name>Alp Ikizler</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Na+ MRI</keyword>
  <keyword>salt stores</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Chlorthalidone</mesh_term>
    <mesh_term>Spironolactone</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>August 15, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/20/NCT02236520/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Spironolactone</title>
          <description>50 mg capsule of Spironolactone administered orally 1 per day for 8 weeks&#xD;
Spironolactone</description>
        </group>
        <group group_id="P2">
          <title>Chlorthalidone</title>
          <description>25 mg capsule of Chlorthalidone administered orally 1 per day for 8 weeks&#xD;
Chlorthalidone</description>
        </group>
        <group group_id="P3">
          <title>Diet</title>
          <description>diet of 6 g salt per day for 8 weeks&#xD;
Diet</description>
        </group>
        <group group_id="P4">
          <title>Placebo</title>
          <description>placebo capsule administered orally 1 per day for 8 weeks&#xD;
Placebo</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="13"/>
                <participants group_id="P3" count="15"/>
                <participants group_id="P4" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="8"/>
                <participants group_id="P3" count="15"/>
                <participants group_id="P4" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Pregnancy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Spironolactone</title>
          <description>50 mg capsule of Spironolactone administered orally 1 per day for 8 weeks&#xD;
Spironolactone</description>
        </group>
        <group group_id="B2">
          <title>Chlorthalidone</title>
          <description>25 mg capsule of Chlorthalidone administered orally 1 per day for 8 weeks&#xD;
Chlorthalidone</description>
        </group>
        <group group_id="B3">
          <title>Diet</title>
          <description>diet of 6 g salt per day for 8 weeks&#xD;
Diet</description>
        </group>
        <group group_id="B4">
          <title>Placebo</title>
          <description>placebo capsule administered orally 1 per day for 8 weeks&#xD;
Placebo</description>
        </group>
        <group group_id="B5">
          <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="16"/>
            <count group_id="B2" value="13"/>
            <count group_id="B3" value="15"/>
            <count group_id="B4" value="15"/>
            <count group_id="B5" value="59"/>
          </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="48" spread="11"/>
                    <measurement group_id="B2" value="49" spread="9"/>
                    <measurement group_id="B3" value="49" spread="13"/>
                    <measurement group_id="B4" value="48" spread="14"/>
                    <measurement group_id="B5" value="48" spread="12"/>
                  </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="11"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="10"/>
                    <measurement group_id="B5" value="40"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="19"/>
                  </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="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="15"/>
                    <measurement group_id="B5" value="58"/>
                  </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 group_id="B4" value="0"/>
                    <measurement group_id="B5" 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 group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="9"/>
                    <measurement group_id="B5" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </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 group_id="B4" value="0"/>
                    <measurement group_id="B5" 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="16"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="15"/>
                    <measurement group_id="B5" value="59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Tissue Sodium Concentration Measured Using Sodium Magnetic Resonance Imaging (NaMRI)</title>
        <description>NaMRI is a sensitive laboratory assessment of the concentration of sodium in tissue</description>
        <time_frame>baseline and 8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Spironolactone</title>
            <description>50 mg capsule of Spironolactone administered orally 1 per day for 8 weeks&#xD;
Spironolactone</description>
          </group>
          <group group_id="O2">
            <title>Chlorthalidone</title>
            <description>25 mg capsule of Chlorthalidone administered orally 1 per day for 8 weeks&#xD;
Chlorthalidone</description>
          </group>
          <group group_id="O3">
            <title>Diet</title>
            <description>diet of 6 g salt per day for 8 weeks&#xD;
Diet</description>
          </group>
          <group group_id="O4">
            <title>Placebo</title>
            <description>placebo capsule administered orally 1 per day for 8 weeks&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Tissue Sodium Concentration Measured Using Sodium Magnetic Resonance Imaging (NaMRI)</title>
          <description>NaMRI is a sensitive laboratory assessment of the concentration of sodium in tissue</description>
          <units>mmol/L</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="15"/>
                <count group_id="O4" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.202" lower_limit="-0.973" upper_limit="1.667"/>
                    <measurement group_id="O2" value="0.430" lower_limit="-1.085" upper_limit="1.285"/>
                    <measurement group_id="O3" value="-1.745" lower_limit="-2.157" upper_limit="-0.219"/>
                    <measurement group_id="O4" value="-0.407" lower_limit="-2.108" upper_limit="1.088"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>8 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Spironolactone</title>
          <description>50 mg capsule of Spironolactone administered orally 1 per day for 8 weeks&#xD;
Spironolactone</description>
        </group>
        <group group_id="E2">
          <title>Chlorthalidone</title>
          <description>25 mg capsule of Chlorthalidone administered orally 1 per day for 8 weeks&#xD;
Chlorthalidone</description>
        </group>
        <group group_id="E3">
          <title>Diet</title>
          <description>diet of 6 g salt per day for 8 weeks&#xD;
Diet</description>
        </group>
        <group group_id="E4">
          <title>Placebo</title>
          <description>placebo capsule administered orally 1 per day for 8 weeks&#xD;
Placebo</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="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <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="13"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="13"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>hypoglycemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>gastrointestinal upset</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>hypokalemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>hyponatremia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>Alp Ikizler</name_or_title>
      <organization>Vanderbilt University Medical Center</organization>
      <phone>(615) 343-7592</phone>
      <email>alp.ikizler@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/NCT02236520
org study id: 141382
nct id: NCT02236520
lead sponsor: 
collaborator: 
has dmc: Yes
Cardiovascular disease is the first common cause of death worldwide. Hypertension is the
      number one driving risk factor. Hypertension has long been associated with dietary salt
      intake. We believe that the accumulation of salt in the interstitium and inside cells
      represents a neglected risk factor, which initiates a pro-inflammatory state, chronically
      increases blood pressure, and leads to systemic energy imbalance. We will explore the concept
      that Na+ storage in the skin and in muscle is associated with increased blood pressure, a
      pro-inflammatory state, and reduced insulin sensitivity. We will do so by addressing the
      following specific aims:

        -  Specific Aim 1: To test the hypothesis that African Americans are characterized by
           increased tissue Na+ storage, which is paralleled by higher blood pressure, reduced
           forearm blood flow, and enhanced pulse wave velocity

        -  Specific Aim 2: To test the hypothesis that treatment with spironolactone reduces tissue
           Na+ content

        -  Specific Aim 3: To test the hypothesis that Na+ storage leads to immune cell activation

        -  Specific Aim 4: To test the hypothesis that the accumulation of salt in skin and muscle
           is associated with decreased insulin sensitivity and propensity to diabetes mellitus
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in Tissue Sodium Concentration Measured Using Sodium Magnetic Resonance Imaging (NaMRI)
time frame: baseline and 8 weeks
description: NaMRI is a sensitive laboratory assessment of the concentration of sodium in tissue
arm group label: Spironolactone
arm group type: Active Comparator
description: 50 mg capsule of Spironolactone administered orally 1 per day for 8 weeks
arm group label: Chlorthalidone
arm group type: Active Comparator
description: 25 mg capsule of Chlorthalidone administered orally 1 per day for 8 weeks
arm group label: Diet
arm group type: Active Comparator
description: diet of 6 g salt per day for 8 weeks
arm group label: Placebo
arm group type: Placebo Comparator
description: placebo capsule administered orally 1 per day for 8 weeks
intervention type: Drug
intervention name: Spironolactone
arm group label: Spironolactone
intervention type: Drug
intervention name: Chlorthalidone
arm group label: Chlorthalidone
intervention type: Dietary Supplement
intervention name: Diet
arm group label: Diet
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 50 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Alp Ikizler, MD
role: Principal Investigator
affiliation: Vanderbilt University
last name: Jens Titze, MD
role: Principal Investigator
affiliation: Vanderbilt University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Vanderbilt University Medical Center
investigator full name: Alp Ikizler
investigator title: Professor
mesh term: Hypertension
mesh term: Chlorthalidone
mesh term: Spironolactone
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 