<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/NCT03837626</url>
  </required_header>
  <id_info>
    <org_study_id>2012990</org_study_id>
    <nct_id>NCT03837626</nct_id>
  </id_info>
  <brief_title>ENAC Blockade and Arterial Stiffness</brief_title>
  <official_title>Estrogen Receptor Alpha Signaling in Endothelial Cells Exacerbates Arterial Stiffening Via Upregulation of ENaC in Insulin Resistant Females</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Missouri-Columbia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Missouri-Columbia</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      To determine whether treatment with the ENaC inhibitor, amiloride, improves endothelial&#xD;
      function and arterial stiffness in obese insulin resistant subjects in a randomized&#xD;
      placebo-controlled trial examining pre and postmenopausal women and age-matched men.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Overweight/obese males, pre- and post-menopausal females with insulin resistance, 30-70 years&#xD;
      of age will be recruited. Following screening, eligible men and women will be randomly&#xD;
      assigned to either amiloride (max dose 5mg) or placebo in a double-blinded design manner.&#xD;
&#xD;
      After randomization, subjects will be scheduled for an outpatient visit to the undergo&#xD;
      baseline assessment of arterial stiffness (carotid femoral pulse wave velocity - cfPWV) and&#xD;
      endothelial function (brachial popliteal artery flow mediated dilation). Subject assessment&#xD;
      will be repeated at 12 weeks and at 24 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 15, 2019</start_date>
  <completion_date type="Anticipated">June 2024</completion_date>
  <primary_completion_date type="Anticipated">June 2024</primary_completion_date>
  <phase>Phase 2/Phase 3</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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Carotid femoral PWV</measure>
    <time_frame>Baseline, 3 months (interim) and 6 months (final)</time_frame>
    <description>It is the gold standard non-invasive index of arterial stiffness. Transit time between carotid and femoral pressure waves is calculated using the foot-to-foot method. cfPWV is calculated as distance traveled by the pulse wave (i.e., femoral location-sternal notch minus sternal notch-carotid location) divided by pulse transit time. All the measurements will be done by the same blinded technician.The goal is to assess changes from baseline when compared to interim and final time point.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Brachial artery flow mediated dilation (FMD)</measure>
    <time_frame>Baseline, 3 months (interim) and 6 months (final)</time_frame>
    <description>The goal is to assess changes from baseline when compared to interim and final time point. ] Brachial artery FMD will be assessed at baseline and at 12-wk. FMD is a measurement of conduit artery endothelial function. FMD is assessed immediately after each PWV measurement. Shear rate AUC until peak diameter is calculated as stimulus for FMD and used in covariate analysis as described. All measurements will be performed, under co-I supervision by the same blinded technician.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Popliteal artery flow mediated dilation (FMD)</measure>
    <time_frame>Baseline, 3 months (interim) and 6 months (final)</time_frame>
    <description>The goal is to assess changes from baseline when compared to interim and final time point. ] Popliteal artery FMD will be assessed at baseline and at 12-wk. FMD is a measurement of conduit artery endothelial function. FMD is assessed immediately after each PWV measurement. Shear rate AUC until peak diameter is calculated as stimulus for FMD and used in covariate analysis as described. All measurements will be performed, under co-I supervision by the same blinded technician.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">157</enrollment>
  <condition>Overweight and Obesity</condition>
  <condition>Insulin Resistance</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>6 months of daily placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Amiloride</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6 months of amiloride (max dose 5 mg) treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo - Cap</intervention_name>
    <description>6 months of 1 pill a day</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Amiloride Pill</intervention_name>
    <description>Max dose of 5 mg a day for 6 months</description>
    <arm_group_label>Amiloride</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  30 to 70 years of age at randomization&#xD;
&#xD;
          -  Body mass index (BMI) 25.1-50 kg/m2 or waist circumference &gt; 88 cm (&gt; 35 in) in women&#xD;
             and &gt;102 cm (&gt;40 in) in men. 3, 4&#xD;
&#xD;
          -  One other characteristic of metabolic syndrome (elevated triglycerides ≥150 mg/dl; HDL&#xD;
             cholesterol &lt;40 mg/dl in men and &lt;50 mg/dl in women; blood pressure ≥130/85 mm Hg or&#xD;
             treatment for hypertension; impaired fasting glucose (≥100 mg/dl)) or fasting insulin&#xD;
             level &gt;10 mU/L (correlates with insulin resistance).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of type 1 or type 2 diabetes&#xD;
&#xD;
          2. Known cardiovascular events within the last 12 months (stroke, acute coronary event,&#xD;
             revascularization, heart failure hospitalization).&#xD;
&#xD;
          3. History of uncontrolled thyroid disease, chronic liver disease (cirrhosis) or GFR &lt;50&#xD;
             ml/min.&#xD;
&#xD;
          4. Use of potassium sparing medications (angiotensin II receptor blockers, angiotensin&#xD;
             converting enzymes inhibitors or mineralocorticoid receptor blockers) or use of&#xD;
             potassium supplements.&#xD;
&#xD;
          5. Active cancer (This criterion does not apply to those subjects with basal cell&#xD;
             carcinoma or stage 1 squamous cell carcinoma of the skin)&#xD;
&#xD;
          6. Excessive alcohol consumption (&gt;14 drinks/week for men, &gt;7 drinks/week for women)&#xD;
&#xD;
          7. Current tobacco use&#xD;
&#xD;
          8. Non controlled hypertension&#xD;
&#xD;
          9. Participation in regular exercise &gt; 3 days/wk per week at a moderate or vigorous&#xD;
             intensity&#xD;
&#xD;
         10. Pregnancy or lactation in women (or women not using contraceptives)&#xD;
&#xD;
         11. Women who plan to become pregnant during the duration of the trial&#xD;
&#xD;
         12. Chronic use of NSAIDs&#xD;
&#xD;
         13. Potassium level &gt; 5.0 mqE/L at time of screening&#xD;
&#xD;
         14. Blood pressure at screening &lt;110/70&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Camila Manrique Acevedo, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Missouri-Columbia</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Camila Manrique Acevedo, MD</last_name>
    <phone>573-8820999</phone>
    <email>manriquec@health.missouri.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Missouri Hospital and Clinics</name>
      <address>
        <city>Columbia</city>
        <state>Missouri</state>
        <zip>65201</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Camila Manrique</last_name>
      <phone>573-882-2273</phone>
      <email>manriquec@health.missouri.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>February 8, 2019</study_first_submitted>
  <study_first_submitted_qc>February 8, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 12, 2019</study_first_posted>
  <last_update_submitted>May 30, 2023</last_update_submitted>
  <last_update_submitted_qc>May 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 31, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Missouri-Columbia</investigator_affiliation>
    <investigator_full_name>Camila Manrique, MD</investigator_full_name>
    <investigator_title>Associate Professor, Endocrinology</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Overweight</mesh_term>
    <mesh_term>Insulin Resistance</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amiloride</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03837626
org study id: 2012990
nct id: NCT03837626
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
To determine whether treatment with the ENaC inhibitor, amiloride, improves endothelial
      function and arterial stiffness in obese insulin resistant subjects in a randomized
      placebo-controlled trial examining pre and postmenopausal women and age-matched men.
Overweight/obese males, pre- and post-menopausal females with insulin resistance, 30-70 years
      of age will be recruited. Following screening, eligible men and women will be randomly
      assigned to either amiloride (max dose 5mg) or placebo in a double-blinded design manner.

      After randomization, subjects will be scheduled for an outpatient visit to the undergo
      baseline assessment of arterial stiffness (carotid femoral pulse wave velocity - cfPWV) and
      endothelial function (brachial popliteal artery flow mediated dilation). Subject assessment
      will be repeated at 12 weeks and at 24 weeks.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Carotid femoral PWV
time frame: Baseline, 3 months (interim) and 6 months (final)
description: It is the gold standard non-invasive index of arterial stiffness. Transit time between carotid and femoral pressure waves is calculated using the foot-to-foot method. cfPWV is calculated as distance traveled by the pulse wave (i.e., femoral location-sternal notch minus sternal notch-carotid location) divided by pulse transit time. All the measurements will be done by the same blinded technician.The goal is to assess changes from baseline when compared to interim and final time point.
measure: Brachial artery flow mediated dilation (FMD)
time frame: Baseline, 3 months (interim) and 6 months (final)
description: The goal is to assess changes from baseline when compared to interim and final time point. ] Brachial artery FMD will be assessed at baseline and at 12-wk. FMD is a measurement of conduit artery endothelial function. FMD is assessed immediately after each PWV measurement. Shear rate AUC until peak diameter is calculated as stimulus for FMD and used in covariate analysis as described. All measurements will be performed, under co-I supervision by the same blinded technician.
measure: Popliteal artery flow mediated dilation (FMD)
time frame: Baseline, 3 months (interim) and 6 months (final)
description: The goal is to assess changes from baseline when compared to interim and final time point. ] Popliteal artery FMD will be assessed at baseline and at 12-wk. FMD is a measurement of conduit artery endothelial function. FMD is assessed immediately after each PWV measurement. Shear rate AUC until peak diameter is calculated as stimulus for FMD and used in covariate analysis as described. All measurements will be performed, under co-I supervision by the same blinded technician.
arm group label: Placebo
arm group type: Placebo Comparator
description: 6 months of daily placebo
arm group label: Amiloride
arm group type: Experimental
description: 6 months of amiloride (max dose 5 mg) treatment
intervention type: Drug
intervention name: Placebo - Cap
description: 6 months of 1 pill a day
arm group label: Placebo
intervention type: Drug
intervention name: Amiloride Pill
description: Max dose of 5 mg a day for 6 months
arm group label: Amiloride
criteria: 
gender: All
minimum age: 30 Years
maximum age: 70 Years
healthy volunteers: No
last name: Camila Manrique Acevedo, MD
role: Principal Investigator
affiliation: University of Missouri-Columbia
last name: Camila Manrique Acevedo, MD
phone: 573-8820999
email: manriquec@health.missouri.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Missouri-Columbia
investigator full name: Camila Manrique, MD
investigator title: Associate Professor, Endocrinology
mesh term: Overweight
mesh term: Insulin Resistance
mesh term: Amiloride