<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/NCT02237079</url>
  </required_header>
  <id_info>
    <org_study_id>WI190523</org_study_id>
    <nct_id>NCT02237079</nct_id>
  </id_info>
  <brief_title>Bazedoxifene/Conjugated Estrogens (BZA/CE) Improvement of Metabolism (BIM)</brief_title>
  <acronym>BIM</acronym>
  <official_title>Bazedoxifene/Conjugated Estrogens (BZA/CE) Improvement of Metabolism (BIM)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tulane University Health Sciences Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tulane University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goal of this pilot clinical study is to perform a randomized placebo-controlled study to&#xD;
      assess the beneficial effect of a 3 month-treatment with Bazedoxifene/Conjugated Estrogens&#xD;
      (BZA/CE) vs. placebo on glucose homeostasis and body composition in 20 post-menopausal women.&#xD;
      The recruitment will be performed at Tulane Health Sciences Center.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2014</start_date>
  <completion_date type="Actual">April 2018</completion_date>
  <primary_completion_date type="Actual">April 2018</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>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Body Mass Index</measure>
    <time_frame>Change at 3 months from baseline</time_frame>
    <description>Body composition will be assessed through change in body mass index at baseline and at 3 months post-treatment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effect of CE/BZA on Body Composition Using Waist-to-hip Ratio</measure>
    <time_frame>Change at 3 months from baseline</time_frame>
    <description>Body composition will be assessed through change in waist-to-hip ratio at baseline and at 3 months post-treatment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Body Composition Using Dual-energy X-ray Absorptiometry (DXA)</measure>
    <time_frame>Change at 3 months from baseline</time_frame>
    <description>Dual-Energy X-ray Absorptiometry was used to assess body composition. DXA uses an x-ray technique to look at the density of the body and can then estimate the amount of lean muscle mass and fat tissue. Body composition will be assessed through change in DXA body composition at baseline and at 3 months post-treatment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Acute Insulin Response to Glucose (AIRg)</measure>
    <time_frame>Change at 3 months from baseline</time_frame>
    <description>This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in acute insulin response to glucose. IVGTT data derived by MINMOD Millennium software. MINMOD: a computer program to calculate insulin sensitivity and pancreatic responsivity from the frequently sampled intravenous glucose tolerance test. Acute Insulin Response (AIRg) to Intravenous Glucose is based on glucose and insulin levels obtained during the frequently sampled intravenous glucose tolerance test and calculated using a mathematical model. AIRg is measured as the magnitude of the insulin response to an intravenous glucose injection following glucose administration. A low AIRg indicates decreased ability of the pancreas to secrete insulin.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Basal Glucose Concentration (Gb)</measure>
    <time_frame>Change at 3 months from baseline</time_frame>
    <description>This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in basal glucose concentration. IVGTT data derived by MINMOD Millennium software.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Disposition Index (DI)</measure>
    <time_frame>Change at 3 months from baseline</time_frame>
    <description>Disposition index (DI) is the product of insulin sensitivity times the amount of insulin secreted in response to blood glucose levels. DI is commonly used as a measure of β-cell function. This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in disposition index (DI). IVGTT data derived by MINMOD Millennium software. DI is based on glucose and insulin levels obtained during the frequently sampled intravenous glucose tolerance test and calculated using a mathematical model. DI is the product of insulin sensitivity and the amount of insulin secreted in response to blood glucose levels. Disposition index is used as a measure of beta cell function and the ability of the body to dispose of a glucose load. A low DI is indicative of a higher risk of developing diabetes.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Insulin Sensitivity (SI) Index</measure>
    <time_frame>Change at 3 months from baseline</time_frame>
    <description>SI indicates the net capacity for insulin to promote the disposal of glucose and to inhibit the endogenous production of glucose. This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in insulin sensitivity (SI) index. IVGTT data derived by MINMOD Millennium software. SI is based on glucose and insulin levels obtained during the frequently sampled intravenous glucose tolerance test and calculated using a mathematical model. SI is a measure of tissue response to circulating insulin in the blood following glucose injection. A low SI signifies low insulin sensitivity and high SI represents high insulin sensitivity.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Homeostatic Model Assessment (HOMA) β-cell Function</measure>
    <time_frame>Change at 3 months from baseline</time_frame>
    <description>The homeostasis model assessment of β-cell function (HOMA-β) is an index of insulin secretory function derived from fasting plasma glucose and insulin concentrations. This will be assessed at baseline and 3 months to measure the change in Homeostatic model assessment (HOMA) β-cell function. (HOMA) β-cell function is a method used to quantify beta-cell function from fasting blood samples of insulin and glucose. Normal levels for (HOMA) β-cell function is 107 or more. Lower numbers mean higher risk of developing diabetes.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Homeostatic Model Assessment (HOMA) Insulin Resistance (IR)</measure>
    <time_frame>Change at 3 months from baseline</time_frame>
    <description>Homeostatic model assessment (HOMA) is a method for assessing β-cell function and insulin resistance (IR) from basal (fasting) glucose and insulin or C-peptide concentrations. This will be assessed at baseline and 3 months to measure the change in Homeostatic model assessment (HOMA) insulin resistance. HOMA IR is a method used to quantify insulin resistance from fasting blood samples of insulin and glucose. Normal levels for HOMA-IR is less than 2.0. Higher levels mean higher risk for developing diabetes.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Fasting Insulin Clearance (FIC)</measure>
    <time_frame>Change at 3 months from baseline</time_frame>
    <description>This will be assessed at baseline and 3 months to measure the change in fasting insulin clearance (FIC). FIC derived from fasting C-peptide to insulin ratio.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Glucose-stimulated Insulin Clearance (GSIC)</measure>
    <time_frame>Change at 3 months from baseline</time_frame>
    <description>This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in glucose-stimulated insulin clearance (GSIC). GSIC derived from molar ratio of C-peptide to insulin area under curve (AUC) over first 20 min of IVGTT.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Measure Change in Serum Biomarkers Panel 1</measure>
    <time_frame>Change at 3 months from baseline</time_frame>
    <description>Systematic inflammation will be measured through change in serum biomarkers (Leptin, Lipocalin 2 (LCN2), plasminogen activator inhibitor-1 (PAI-1), Intact OCN) taken at baseline and 3 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measure Change in Serum Biomarkers Panel 2</measure>
    <time_frame>Change at 3 months from baseline</time_frame>
    <description>Systematic inflammation will be measured through change in serum biomarkers (Adiponectin, RBP4) taken at baseline and 3 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measure Change in Leptin:Adiponectin Ratio (LAR)</measure>
    <time_frame>Change at 3 months from baseline</time_frame>
    <description>Systematic inflammation will be measured through change in leptin:adiponectin ratio (LAR) taken at baseline and 3 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measure Change in Fibroblast Growth Factor-21 (FGF-21)</measure>
    <time_frame>Change at 3 months from baseline</time_frame>
    <description>Systematic inflammation will be measured through change in Fibroblast growth factor-21 (FGF-21) taken at baseline and 3 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measure Change in C-Reactive Protein (CRP)</measure>
    <time_frame>Change at 3 months from baseline</time_frame>
    <description>Systematic inflammation will be measured through change in C-Reactive Protein (CRP) taken at baseline and 3 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measure Change in Thiobarbituric Acid Reactive Substance (TBARS)</measure>
    <time_frame>Change at 3 months from baseline</time_frame>
    <description>Systematic inflammation will be measured through change in Thiobarbituric acid reactive substance (TBARS) taken at baseline and 3 months.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">17</enrollment>
  <condition>Obesity</condition>
  <condition>Glucose Homeostasis</condition>
  <condition>Postmenopausal Symptoms</condition>
  <arm_group>
    <arm_group_label>Bazedoxifene/Conjugated Estrogens (BZA/CE)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants assigned to BZA/CE will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg. BZA/CE (bazedoxifene/conjugated estrogens) tablets, 0.45 mg/20 mg are oval, biconvex, pink tablets, branded with &quot;0.45/20&quot; in black ink on one side. The recommended and only FDA approved dosage is one BZA/CE tablet daily, taken without regard to meals. Tablets should be swallowed whole. If a dose of BZA/CE is missed, participants will be instructed to take it as soon as remembered unless it is almost time for the next scheduled dose. They should not take two doses at the same time. The dose is one tablet per day independent of weight and fat mass. Participants will be provided with information about BZA/CE and its potential side effects and contraindications.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants assigned to placebo will receive a daily tablet that matches the BZA/CE to maintain the blind. Placebo tablets, 0.45 mg/20 mg are oval, biconvex, pink tablets, branded with &quot;0.45/20&quot; in black ink on one side. Also to assure the blind is maintain, participants in the placebo group will be given the same instructions for taking the study medication.Tablets should be swallowed whole. If a dose, participants will be instructed to take it as soon as remembered unless it is almost time for the next scheduled dose. They should not take two doses at the same time. The dose is one tablet per day independent of weight and fat mass. Participants will be provided with information about BZA/CE and its potential side effects and contraindications, again to maintain the blind.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bazedoxifene/Conjugated Estrogens (BZA/CE)</intervention_name>
    <description>Daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.</description>
    <arm_group_label>Bazedoxifene/Conjugated Estrogens (BZA/CE)</arm_group_label>
    <other_name>DUAVEE</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Tablet</intervention_name>
    <description>Daily placebo tablet</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Post-menopausal women (&lt;5y since final menstrual period) with age between 50-60y&#xD;
&#xD;
          -  Symptomatic (hot flashes, vaginal dryness) or asymptomatic&#xD;
&#xD;
          -  BMI 26-45 kg/m2 (Overweight, Obesity I and Obesity II)&#xD;
&#xD;
          -  Fasting glucose &lt;125mg/dl&#xD;
&#xD;
          -  Triglycerides &lt;200mg/dl&#xD;
&#xD;
          -  Normal mammogram within past 12 months&#xD;
&#xD;
          -  Physician clearance&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Amenorrhea from other causes (Hyperandrogenemia and anovulation)&#xD;
&#xD;
          -  type 2 and type 1 diabetes&#xD;
&#xD;
          -  Medications: diabetes or diabetic drugs, dyslipidemia, estrogen/progestin therapy,&#xD;
             antidepressants and antipsychotics, antiretroviral (HIV), oral steroids, weight loss&#xD;
             drugs&#xD;
&#xD;
          -  ≤ 3 month washout of birth control pill (often prescribed for postmenopausal symptoms)&#xD;
&#xD;
          -  Hysterectomy (partial or complete)&#xD;
&#xD;
          -  Contraindications to estrogen treatment (unusual vaginal bleeding, blot clots, hepatic&#xD;
             disease, bleeding disorder, past/present history of breast or uterine cancer,&#xD;
             pregnant, breastfeeding)&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Franck Mauvais-Jarvis, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Tulane University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Tulane University Clinical Translational Unit</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>August 26, 2014</study_first_submitted>
  <study_first_submitted_qc>September 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 11, 2014</study_first_posted>
  <results_first_submitted>February 28, 2023</results_first_submitted>
  <results_first_submitted_qc>May 30, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">June 26, 2023</results_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">June 26, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Tulane University Health Sciences Center</investigator_affiliation>
    <investigator_full_name>Franck Mauvais-Jarvis</investigator_full_name>
    <investigator_title>Professor of Medicine</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bazedoxifene</mesh_term>
    <mesh_term>Estrogens</mesh_term>
    <mesh_term>Estrogens, Conjugated (USP)</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>At this time there is no plan to share individual participant data (IPD)</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 26, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/79/NCT02237079/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Bazedoxifene/Conjugated Estrogens (CE/BZA)</title>
          <description>Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Conjugated Estrogens/Bazedoxifene (CE/BZA)</title>
          <description>Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.</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="7"/>
            <count group_id="B2" value="5"/>
            <count group_id="B3" value="12"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <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="7"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 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_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="54" lower_limit="52" upper_limit="56"/>
                    <measurement group_id="B2" value="55" lower_limit="54" upper_limit="58"/>
                    <measurement group_id="B3" value="54.5" lower_limit="53" upper_limit="56.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>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_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_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_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="10"/>
                  </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_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>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="7"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Years since last menstrual period (LMP)</title>
          <units>Years</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2" lower_limit="1.4" upper_limit="3.8"/>
                    <measurement group_id="B2" value="4.5" lower_limit="2.1" upper_limit="4.8"/>
                    <measurement group_id="B3" value="2.7" lower_limit="1.7" upper_limit="4.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Waist-to-hip ratio</title>
          <units>Ratio</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0.9" lower_limit="0.82" upper_limit="0.95"/>
                    <measurement group_id="B2" value="0.84" lower_limit="0.82" upper_limit="0.85"/>
                    <measurement group_id="B3" value="0.85" lower_limit="0.82" upper_limit="0.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index (BMI)</title>
          <units>Kg/m^2</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="33" lower_limit="30.6" upper_limit="37"/>
                    <measurement group_id="B2" value="31.2" lower_limit="30.7" upper_limit="38.6"/>
                    <measurement group_id="B3" value="32.4" lower_limit="30.7" upper_limit="37.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Waist circumference</title>
          <units>Cm</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="109.2" lower_limit="91.4" upper_limit="114.3"/>
                    <measurement group_id="B2" value="106.7" lower_limit="92" upper_limit="116.8"/>
                    <measurement group_id="B3" value="108" lower_limit="91.7" upper_limit="115.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Fasting glucose</title>
          <units>mg/dL</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="94" lower_limit="83" upper_limit="114"/>
                    <measurement group_id="B2" value="88" lower_limit="84" upper_limit="98"/>
                    <measurement group_id="B3" value="93.5" lower_limit="83.5" upper_limit="108"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Total cholesterol</title>
          <units>mg/dL</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="208" lower_limit="167" upper_limit="218"/>
                    <measurement group_id="B2" value="216" lower_limit="202" upper_limit="245"/>
                    <measurement group_id="B3" value="211.5" lower_limit="190.5" upper_limit="231.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>High-density lipoprotein (HDL)</title>
          <units>mg/dL</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="60" lower_limit="45" upper_limit="69"/>
                    <measurement group_id="B2" value="66" lower_limit="58" upper_limit="73"/>
                    <measurement group_id="B3" value="63" lower_limit="49.5" upper_limit="71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Low-density lipoprotein (LDL)</title>
          <units>mg/dL</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="120" lower_limit="99" upper_limit="148"/>
                    <measurement group_id="B2" value="128" lower_limit="115" upper_limit="147"/>
                    <measurement group_id="B3" value="124" lower_limit="111.5" upper_limit="147.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Triglycerides</title>
          <units>mg/dL</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="124" lower_limit="81" upper_limit="131"/>
                    <measurement group_id="B2" value="103" lower_limit="102" upper_limit="125"/>
                    <measurement group_id="B3" value="113.5" lower_limit="82.5" upper_limit="128.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Body Mass Index</title>
        <description>Body composition will be assessed through change in body mass index at baseline and at 3 months post-treatment.</description>
        <time_frame>Change at 3 months from baseline</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Bazedoxifene/Conjugated Estrogens (CE/BZA)</title>
            <description>Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Body Mass Index</title>
          <description>Body composition will be assessed through change in body mass index at baseline and at 3 months post-treatment.</description>
          <units>Kg/m^2</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="7"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.2" lower_limit="-0.5" upper_limit="0.3"/>
                    <measurement group_id="O2" value="-0.5" lower_limit="-0.6" upper_limit="-0.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Effect of CE/BZA on Body Composition Using Waist-to-hip Ratio</title>
        <description>Body composition will be assessed through change in waist-to-hip ratio at baseline and at 3 months post-treatment.</description>
        <time_frame>Change at 3 months from baseline</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Bazedoxifene/Conjugated Estrogens (CE/BZA)</title>
            <description>Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.</description>
          </group>
        </group_list>
        <measure>
          <title>Effect of CE/BZA on Body Composition Using Waist-to-hip Ratio</title>
          <description>Body composition will be assessed through change in waist-to-hip ratio at baseline and at 3 months post-treatment.</description>
          <units>Ratio</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="7"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.05" lower_limit="-0.06" upper_limit="0.03"/>
                    <measurement group_id="O2" value="0.00" lower_limit="-0.02" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Body Composition Using Dual-energy X-ray Absorptiometry (DXA)</title>
        <description>Dual-Energy X-ray Absorptiometry was used to assess body composition. DXA uses an x-ray technique to look at the density of the body and can then estimate the amount of lean muscle mass and fat tissue. Body composition will be assessed through change in DXA body composition at baseline and at 3 months post-treatment.</description>
        <time_frame>Change at 3 months from baseline</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Bazedoxifene/Conjugated Estrogens (CE/BZA)</title>
            <description>Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Body Composition Using Dual-energy X-ray Absorptiometry (DXA)</title>
          <description>Dual-Energy X-ray Absorptiometry was used to assess body composition. DXA uses an x-ray technique to look at the density of the body and can then estimate the amount of lean muscle mass and fat tissue. Body composition will be assessed through change in DXA body composition at baseline and at 3 months post-treatment.</description>
          <units>g</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="7"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Total fat mass</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="273" lower_limit="-571" upper_limit="974"/>
                    <measurement group_id="O2" value="-1408" lower_limit="-1932" upper_limit="467"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Android fat mass</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5" lower_limit="-226" upper_limit="611"/>
                    <measurement group_id="O2" value="-131" lower_limit="-452" upper_limit="-86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Gynoid fat mass</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-26" lower_limit="-550" upper_limit="279"/>
                    <measurement group_id="O2" value="-178" lower_limit="-189" upper_limit="-116"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visceral adipose tissue (VAT) mass</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46" lower_limit="-63" upper_limit="118"/>
                    <measurement group_id="O2" value="-47" lower_limit="-134" upper_limit="-23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Acute Insulin Response to Glucose (AIRg)</title>
        <description>This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in acute insulin response to glucose. IVGTT data derived by MINMOD Millennium software. MINMOD: a computer program to calculate insulin sensitivity and pancreatic responsivity from the frequently sampled intravenous glucose tolerance test. Acute Insulin Response (AIRg) to Intravenous Glucose is based on glucose and insulin levels obtained during the frequently sampled intravenous glucose tolerance test and calculated using a mathematical model. AIRg is measured as the magnitude of the insulin response to an intravenous glucose injection following glucose administration. A low AIRg indicates decreased ability of the pancreas to secrete insulin.</description>
        <time_frame>Change at 3 months from baseline</time_frame>
        <population>Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6).</population>
        <group_list>
          <group group_id="O1">
            <title>Bazedoxifene/Conjugated Estrogens (CE/BZA)</title>
            <description>Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Acute Insulin Response to Glucose (AIRg)</title>
          <description>This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in acute insulin response to glucose. IVGTT data derived by MINMOD Millennium software. MINMOD: a computer program to calculate insulin sensitivity and pancreatic responsivity from the frequently sampled intravenous glucose tolerance test. Acute Insulin Response (AIRg) to Intravenous Glucose is based on glucose and insulin levels obtained during the frequently sampled intravenous glucose tolerance test and calculated using a mathematical model. AIRg is measured as the magnitude of the insulin response to an intravenous glucose injection following glucose administration. A low AIRg indicates decreased ability of the pancreas to secrete insulin.</description>
          <population>Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6).</population>
          <units>uU/l^-1.min^-1</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="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="189" lower_limit="-31" upper_limit="444"/>
                    <measurement group_id="O2" value="-25" lower_limit="-47" upper_limit="-9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Basal Glucose Concentration (Gb)</title>
        <description>This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in basal glucose concentration. IVGTT data derived by MINMOD Millennium software.</description>
        <time_frame>Change at 3 months from baseline</time_frame>
        <population>Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6).</population>
        <group_list>
          <group group_id="O1">
            <title>Bazedoxifene/Conjugated Estrogens (CE/BZA)</title>
            <description>Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Basal Glucose Concentration (Gb)</title>
          <description>This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in basal glucose concentration. IVGTT data derived by MINMOD Millennium software.</description>
          <population>Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6).</population>
          <units>mg/dL</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="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.2" lower_limit="-9.2" upper_limit="-1.7"/>
                    <measurement group_id="O2" value="2.7" lower_limit="0.9" upper_limit="4.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Disposition Index (DI)</title>
        <description>Disposition index (DI) is the product of insulin sensitivity times the amount of insulin secreted in response to blood glucose levels. DI is commonly used as a measure of β-cell function. This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in disposition index (DI). IVGTT data derived by MINMOD Millennium software. DI is based on glucose and insulin levels obtained during the frequently sampled intravenous glucose tolerance test and calculated using a mathematical model. DI is the product of insulin sensitivity and the amount of insulin secreted in response to blood glucose levels. Disposition index is used as a measure of beta cell function and the ability of the body to dispose of a glucose load. A low DI is indicative of a higher risk of developing diabetes.</description>
        <time_frame>Change at 3 months from baseline</time_frame>
        <population>Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6).</population>
        <group_list>
          <group group_id="O1">
            <title>Bazedoxifene/Conjugated Estrogens (CE/BZA)</title>
            <description>Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Disposition Index (DI)</title>
          <description>Disposition index (DI) is the product of insulin sensitivity times the amount of insulin secreted in response to blood glucose levels. DI is commonly used as a measure of β-cell function. This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in disposition index (DI). IVGTT data derived by MINMOD Millennium software. DI is based on glucose and insulin levels obtained during the frequently sampled intravenous glucose tolerance test and calculated using a mathematical model. DI is the product of insulin sensitivity and the amount of insulin secreted in response to blood glucose levels. Disposition index is used as a measure of beta cell function and the ability of the body to dispose of a glucose load. A low DI is indicative of a higher risk of developing diabetes.</description>
          <population>Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6).</population>
          <units>Index</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="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="500" lower_limit="-19" upper_limit="841"/>
                    <measurement group_id="O2" value="267" lower_limit="28" upper_limit="572"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Insulin Sensitivity (SI) Index</title>
        <description>SI indicates the net capacity for insulin to promote the disposal of glucose and to inhibit the endogenous production of glucose. This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in insulin sensitivity (SI) index. IVGTT data derived by MINMOD Millennium software. SI is based on glucose and insulin levels obtained during the frequently sampled intravenous glucose tolerance test and calculated using a mathematical model. SI is a measure of tissue response to circulating insulin in the blood following glucose injection. A low SI signifies low insulin sensitivity and high SI represents high insulin sensitivity.</description>
        <time_frame>Change at 3 months from baseline</time_frame>
        <population>Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6).</population>
        <group_list>
          <group group_id="O1">
            <title>Bazedoxifene/Conjugated Estrogens (CE/BZA)</title>
            <description>Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Insulin Sensitivity (SI) Index</title>
          <description>SI indicates the net capacity for insulin to promote the disposal of glucose and to inhibit the endogenous production of glucose. This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in insulin sensitivity (SI) index. IVGTT data derived by MINMOD Millennium software. SI is based on glucose and insulin levels obtained during the frequently sampled intravenous glucose tolerance test and calculated using a mathematical model. SI is a measure of tissue response to circulating insulin in the blood following glucose injection. A low SI signifies low insulin sensitivity and high SI represents high insulin sensitivity.</description>
          <population>Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6).</population>
          <units>uU/L^-1.min^-1</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="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.24" lower_limit="-1.50" upper_limit="0.19"/>
                    <measurement group_id="O2" value="1.35" lower_limit="1.12" upper_limit="1.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Homeostatic Model Assessment (HOMA) β-cell Function</title>
        <description>The homeostasis model assessment of β-cell function (HOMA-β) is an index of insulin secretory function derived from fasting plasma glucose and insulin concentrations. This will be assessed at baseline and 3 months to measure the change in Homeostatic model assessment (HOMA) β-cell function. (HOMA) β-cell function is a method used to quantify beta-cell function from fasting blood samples of insulin and glucose. Normal levels for (HOMA) β-cell function is 107 or more. Lower numbers mean higher risk of developing diabetes.</description>
        <time_frame>Change at 3 months from baseline</time_frame>
        <population>Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6).</population>
        <group_list>
          <group group_id="O1">
            <title>Bazedoxifene/Conjugated Estrogens (CE/BZA)</title>
            <description>Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Homeostatic Model Assessment (HOMA) β-cell Function</title>
          <description>The homeostasis model assessment of β-cell function (HOMA-β) is an index of insulin secretory function derived from fasting plasma glucose and insulin concentrations. This will be assessed at baseline and 3 months to measure the change in Homeostatic model assessment (HOMA) β-cell function. (HOMA) β-cell function is a method used to quantify beta-cell function from fasting blood samples of insulin and glucose. Normal levels for (HOMA) β-cell function is 107 or more. Lower numbers mean higher risk of developing diabetes.</description>
          <population>Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6).</population>
          <units>uU/mM</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="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.5" lower_limit="-0.9" upper_limit="320.6"/>
                    <measurement group_id="O2" value="-25.5" lower_limit="-39.9" upper_limit="0.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Homeostatic Model Assessment (HOMA) Insulin Resistance (IR)</title>
        <description>Homeostatic model assessment (HOMA) is a method for assessing β-cell function and insulin resistance (IR) from basal (fasting) glucose and insulin or C-peptide concentrations. This will be assessed at baseline and 3 months to measure the change in Homeostatic model assessment (HOMA) insulin resistance. HOMA IR is a method used to quantify insulin resistance from fasting blood samples of insulin and glucose. Normal levels for HOMA-IR is less than 2.0. Higher levels mean higher risk for developing diabetes.</description>
        <time_frame>Change at 3 months from baseline</time_frame>
        <population>Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6).</population>
        <group_list>
          <group group_id="O1">
            <title>Bazedoxifene/Conjugated Estrogens (CE/BZA)</title>
            <description>Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Homeostatic Model Assessment (HOMA) Insulin Resistance (IR)</title>
          <description>Homeostatic model assessment (HOMA) is a method for assessing β-cell function and insulin resistance (IR) from basal (fasting) glucose and insulin or C-peptide concentrations. This will be assessed at baseline and 3 months to measure the change in Homeostatic model assessment (HOMA) insulin resistance. HOMA IR is a method used to quantify insulin resistance from fasting blood samples of insulin and glucose. Normal levels for HOMA-IR is less than 2.0. Higher levels mean higher risk for developing diabetes.</description>
          <population>Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6).</population>
          <units>mM.uU/L^-2</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="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.15" lower_limit="-0.18" upper_limit="0.34"/>
                    <measurement group_id="O2" value="-0.01" lower_limit="-0.10" upper_limit="0.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Fasting Insulin Clearance (FIC)</title>
        <description>This will be assessed at baseline and 3 months to measure the change in fasting insulin clearance (FIC). FIC derived from fasting C-peptide to insulin ratio.</description>
        <time_frame>Change at 3 months from baseline</time_frame>
        <population>Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6).</population>
        <group_list>
          <group group_id="O1">
            <title>Bazedoxifene/Conjugated Estrogens (CE/BZA)</title>
            <description>Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Fasting Insulin Clearance (FIC)</title>
          <description>This will be assessed at baseline and 3 months to measure the change in fasting insulin clearance (FIC). FIC derived from fasting C-peptide to insulin ratio.</description>
          <population>Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6).</population>
          <units>Ratio</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="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.50" lower_limit="-11.56" upper_limit="0.78"/>
                    <measurement group_id="O2" value="-0.25" lower_limit="-0.70" upper_limit="-0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Glucose-stimulated Insulin Clearance (GSIC)</title>
        <description>This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in glucose-stimulated insulin clearance (GSIC). GSIC derived from molar ratio of C-peptide to insulin area under curve (AUC) over first 20 min of IVGTT.</description>
        <time_frame>Change at 3 months from baseline</time_frame>
        <population>Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6).</population>
        <group_list>
          <group group_id="O1">
            <title>Bazedoxifene/Conjugated Estrogens (CE/BZA)</title>
            <description>Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Glucose-stimulated Insulin Clearance (GSIC)</title>
          <description>This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in glucose-stimulated insulin clearance (GSIC). GSIC derived from molar ratio of C-peptide to insulin area under curve (AUC) over first 20 min of IVGTT.</description>
          <population>Note that for technical reasons, the IVGTT serum was processed in only 11 of 12 subjects (CE/BZA n = 6).</population>
          <units>Ratio</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="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-32.8" lower_limit="-123.6" upper_limit="6.9"/>
                    <measurement group_id="O2" value="-1.85" lower_limit="-20.5" upper_limit="25.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Measure Change in Serum Biomarkers Panel 1</title>
        <description>Systematic inflammation will be measured through change in serum biomarkers (Leptin, Lipocalin 2 (LCN2), plasminogen activator inhibitor-1 (PAI-1), Intact OCN) taken at baseline and 3 months.</description>
        <time_frame>Change at 3 months from baseline</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Bazedoxifene/Conjugated Estrogens (CE/BZA)</title>
            <description>Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.</description>
          </group>
        </group_list>
        <measure>
          <title>Measure Change in Serum Biomarkers Panel 1</title>
          <description>Systematic inflammation will be measured through change in serum biomarkers (Leptin, Lipocalin 2 (LCN2), plasminogen activator inhibitor-1 (PAI-1), Intact OCN) taken at baseline and 3 months.</description>
          <units>ng/mL</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="7"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Leptin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.6" lower_limit="-7.2" upper_limit="9.5"/>
                    <measurement group_id="O2" value="0.7" lower_limit="-0.1" upper_limit="10.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lipocalin-2 (LCN2)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.7" lower_limit="-3" upper_limit="3.5"/>
                    <measurement group_id="O2" value="-3.8" lower_limit="-4.9" upper_limit="2.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Plasminogen activator inhibitor-1 (PAI-1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.8" lower_limit="-5.2" upper_limit="-1.4"/>
                    <measurement group_id="O2" value="1.3" lower_limit="-0.4" upper_limit="3.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Osteocalcin (OCN)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8" lower_limit="-0.7" upper_limit="3.1"/>
                    <measurement group_id="O2" value="-0.9" lower_limit="-1.1" upper_limit="2.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Measure Change in Serum Biomarkers Panel 2</title>
        <description>Systematic inflammation will be measured through change in serum biomarkers (Adiponectin, RBP4) taken at baseline and 3 months.</description>
        <time_frame>Change at 3 months from baseline</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Bazedoxifene/Conjugated Estrogens (CE/BZA)</title>
            <description>Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.</description>
          </group>
        </group_list>
        <measure>
          <title>Measure Change in Serum Biomarkers Panel 2</title>
          <description>Systematic inflammation will be measured through change in serum biomarkers (Adiponectin, RBP4) taken at baseline and 3 months.</description>
          <units>ug/mL</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="7"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Retinol binding protein 4 (RBP4)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.4" lower_limit="-5.6" upper_limit="14.5"/>
                    <measurement group_id="O2" value="-4.0" lower_limit="-24.1" upper_limit="4.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Adiponectin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.4" lower_limit="-2.8" upper_limit="-0.5"/>
                    <measurement group_id="O2" value="-2.5" lower_limit="-2.6" upper_limit="-0.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Measure Change in Leptin:Adiponectin Ratio (LAR)</title>
        <description>Systematic inflammation will be measured through change in leptin:adiponectin ratio (LAR) taken at baseline and 3 months.</description>
        <time_frame>Change at 3 months from baseline</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Bazedoxifene/Conjugated Estrogens (CE/BZA)</title>
            <description>Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.</description>
          </group>
        </group_list>
        <measure>
          <title>Measure Change in Leptin:Adiponectin Ratio (LAR)</title>
          <description>Systematic inflammation will be measured through change in leptin:adiponectin ratio (LAR) taken at baseline and 3 months.</description>
          <units>Ratio</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="7"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.71" lower_limit="-0.04" upper_limit="4.96"/>
                    <measurement group_id="O2" value="1.55" lower_limit="0.02" upper_limit="4.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Measure Change in Fibroblast Growth Factor-21 (FGF-21)</title>
        <description>Systematic inflammation will be measured through change in Fibroblast growth factor-21 (FGF-21) taken at baseline and 3 months.</description>
        <time_frame>Change at 3 months from baseline</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Bazedoxifene/Conjugated Estrogens (CE/BZA)</title>
            <description>Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.</description>
          </group>
        </group_list>
        <measure>
          <title>Measure Change in Fibroblast Growth Factor-21 (FGF-21)</title>
          <description>Systematic inflammation will be measured through change in Fibroblast growth factor-21 (FGF-21) taken at baseline and 3 months.</description>
          <units>pg/mL</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="7"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-134" lower_limit="-208" upper_limit="24"/>
                    <measurement group_id="O2" value="-89" lower_limit="-226" upper_limit="-48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Measure Change in C-Reactive Protein (CRP)</title>
        <description>Systematic inflammation will be measured through change in C-Reactive Protein (CRP) taken at baseline and 3 months.</description>
        <time_frame>Change at 3 months from baseline</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Bazedoxifene/Conjugated Estrogens (CE/BZA)</title>
            <description>Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.</description>
          </group>
        </group_list>
        <measure>
          <title>Measure Change in C-Reactive Protein (CRP)</title>
          <description>Systematic inflammation will be measured through change in C-Reactive Protein (CRP) taken at baseline and 3 months.</description>
          <units>mg/mL</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="7"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.41" lower_limit="-2.66" upper_limit="0.45"/>
                    <measurement group_id="O2" value="-0.39" lower_limit="-0.82" upper_limit="-0.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Measure Change in Thiobarbituric Acid Reactive Substance (TBARS)</title>
        <description>Systematic inflammation will be measured through change in Thiobarbituric acid reactive substance (TBARS) taken at baseline and 3 months.</description>
        <time_frame>Change at 3 months from baseline</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Bazedoxifene/Conjugated Estrogens (CE/BZA)</title>
            <description>Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.</description>
          </group>
        </group_list>
        <measure>
          <title>Measure Change in Thiobarbituric Acid Reactive Substance (TBARS)</title>
          <description>Systematic inflammation will be measured through change in Thiobarbituric acid reactive substance (TBARS) taken at baseline and 3 months.</description>
          <units>nmol/mL</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="7"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.7" lower_limit="-3.3" upper_limit="-0.4"/>
                    <measurement group_id="O2" value="-1.2" lower_limit="-1.2" upper_limit="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>The data were collected during baseline visit (during IVGTT for 3 hours) and then again they were collected at the 3 months visit (during IVGTT for 3 hours).</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Bazedoxifene/Conjugated Estrogens (CE/BZA)</title>
          <description>Participants assigned to CE/BZA will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Participants assigned to placebo will receive a daily tablet that matches the CE/BZA to maintain the blind.</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="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Lower Insulin dose given</sub_title>
                <description>During the preparations for IVGTT, incorrect (lower) weight of the subject was used to calculate insulin dose, therefore patient was given lower than recommended insulin dose during IVGTT. This event did not affect patient's wellbeing or health.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </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>Dr. Franck Mauvais-Jarvis</name_or_title>
      <organization>Tulane University</organization>
      <phone>504-988-5990</phone>
      <email>fmauvais@tulane.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/NCT02237079
org study id: WI190523
nct id: NCT02237079
lead sponsor: 
has dmc: No
The goal of this pilot clinical study is to perform a randomized placebo-controlled study to
      assess the beneficial effect of a 3 month-treatment with Bazedoxifene/Conjugated Estrogens
      (BZA/CE) vs. placebo on glucose homeostasis and body composition in 20 post-menopausal women.
      The recruitment will be performed at Tulane Health Sciences Center.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Investigator)
measure: Change in Body Mass Index
time frame: Change at 3 months from baseline
description: Body composition will be assessed through change in body mass index at baseline and at 3 months post-treatment.
measure: Effect of CE/BZA on Body Composition Using Waist-to-hip Ratio
time frame: Change at 3 months from baseline
description: Body composition will be assessed through change in waist-to-hip ratio at baseline and at 3 months post-treatment.
measure: Change in Body Composition Using Dual-energy X-ray Absorptiometry (DXA)
time frame: Change at 3 months from baseline
description: Dual-Energy X-ray Absorptiometry was used to assess body composition. DXA uses an x-ray technique to look at the density of the body and can then estimate the amount of lean muscle mass and fat tissue. Body composition will be assessed through change in DXA body composition at baseline and at 3 months post-treatment.
measure: Change in Acute Insulin Response to Glucose (AIRg)
time frame: Change at 3 months from baseline
description: This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in acute insulin response to glucose. IVGTT data derived by MINMOD Millennium software. MINMOD: a computer program to calculate insulin sensitivity and pancreatic responsivity from the frequently sampled intravenous glucose tolerance test. Acute Insulin Response (AIRg) to Intravenous Glucose is based on glucose and insulin levels obtained during the frequently sampled intravenous glucose tolerance test and calculated using a mathematical model. AIRg is measured as the magnitude of the insulin response to an intravenous glucose injection following glucose administration. A low AIRg indicates decreased ability of the pancreas to secrete insulin.
measure: Change in Basal Glucose Concentration (Gb)
time frame: Change at 3 months from baseline
description: This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in basal glucose concentration. IVGTT data derived by MINMOD Millennium software.
measure: Change in Disposition Index (DI)
time frame: Change at 3 months from baseline
description: Disposition index (DI) is the product of insulin sensitivity times the amount of insulin secreted in response to blood glucose levels. DI is commonly used as a measure of β-cell function. This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in disposition index (DI). IVGTT data derived by MINMOD Millennium software. DI is based on glucose and insulin levels obtained during the frequently sampled intravenous glucose tolerance test and calculated using a mathematical model. DI is the product of insulin sensitivity and the amount of insulin secreted in response to blood glucose levels. Disposition index is used as a measure of beta cell function and the ability of the body to dispose of a glucose load. A low DI is indicative of a higher risk of developing diabetes.
measure: Change in Insulin Sensitivity (SI) Index
time frame: Change at 3 months from baseline
description: SI indicates the net capacity for insulin to promote the disposal of glucose and to inhibit the endogenous production of glucose. This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in insulin sensitivity (SI) index. IVGTT data derived by MINMOD Millennium software. SI is based on glucose and insulin levels obtained during the frequently sampled intravenous glucose tolerance test and calculated using a mathematical model. SI is a measure of tissue response to circulating insulin in the blood following glucose injection. A low SI signifies low insulin sensitivity and high SI represents high insulin sensitivity.
measure: Change in Homeostatic Model Assessment (HOMA) β-cell Function
time frame: Change at 3 months from baseline
description: The homeostasis model assessment of β-cell function (HOMA-β) is an index of insulin secretory function derived from fasting plasma glucose and insulin concentrations. This will be assessed at baseline and 3 months to measure the change in Homeostatic model assessment (HOMA) β-cell function. (HOMA) β-cell function is a method used to quantify beta-cell function from fasting blood samples of insulin and glucose. Normal levels for (HOMA) β-cell function is 107 or more. Lower numbers mean higher risk of developing diabetes.
measure: Change in Homeostatic Model Assessment (HOMA) Insulin Resistance (IR)
time frame: Change at 3 months from baseline
description: Homeostatic model assessment (HOMA) is a method for assessing β-cell function and insulin resistance (IR) from basal (fasting) glucose and insulin or C-peptide concentrations. This will be assessed at baseline and 3 months to measure the change in Homeostatic model assessment (HOMA) insulin resistance. HOMA IR is a method used to quantify insulin resistance from fasting blood samples of insulin and glucose. Normal levels for HOMA-IR is less than 2.0. Higher levels mean higher risk for developing diabetes.
measure: Change in Fasting Insulin Clearance (FIC)
time frame: Change at 3 months from baseline
description: This will be assessed at baseline and 3 months to measure the change in fasting insulin clearance (FIC). FIC derived from fasting C-peptide to insulin ratio.
measure: Change in Glucose-stimulated Insulin Clearance (GSIC)
time frame: Change at 3 months from baseline
description: This will be assessed through an IV Glucose Tolerance Test (IVGTT) conducted at baseline and 3 months to measure the change in glucose-stimulated insulin clearance (GSIC). GSIC derived from molar ratio of C-peptide to insulin area under curve (AUC) over first 20 min of IVGTT.
measure: Measure Change in Serum Biomarkers Panel 1
time frame: Change at 3 months from baseline
description: Systematic inflammation will be measured through change in serum biomarkers (Leptin, Lipocalin 2 (LCN2), plasminogen activator inhibitor-1 (PAI-1), Intact OCN) taken at baseline and 3 months.
measure: Measure Change in Serum Biomarkers Panel 2
time frame: Change at 3 months from baseline
description: Systematic inflammation will be measured through change in serum biomarkers (Adiponectin, RBP4) taken at baseline and 3 months.
measure: Measure Change in Leptin:Adiponectin Ratio (LAR)
time frame: Change at 3 months from baseline
description: Systematic inflammation will be measured through change in leptin:adiponectin ratio (LAR) taken at baseline and 3 months.
measure: Measure Change in Fibroblast Growth Factor-21 (FGF-21)
time frame: Change at 3 months from baseline
description: Systematic inflammation will be measured through change in Fibroblast growth factor-21 (FGF-21) taken at baseline and 3 months.
measure: Measure Change in C-Reactive Protein (CRP)
time frame: Change at 3 months from baseline
description: Systematic inflammation will be measured through change in C-Reactive Protein (CRP) taken at baseline and 3 months.
measure: Measure Change in Thiobarbituric Acid Reactive Substance (TBARS)
time frame: Change at 3 months from baseline
description: Systematic inflammation will be measured through change in Thiobarbituric acid reactive substance (TBARS) taken at baseline and 3 months.
arm group label: Bazedoxifene/Conjugated Estrogens (BZA/CE)
arm group type: Experimental
description: Participants assigned to BZA/CE will receive a daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg. BZA/CE (bazedoxifene/conjugated estrogens) tablets, 0.45 mg/20 mg are oval, biconvex, pink tablets, branded with "0.45/20" in black ink on one side. The recommended and only FDA approved dosage is one BZA/CE tablet daily, taken without regard to meals. Tablets should be swallowed whole. If a dose of BZA/CE is missed, participants will be instructed to take it as soon as remembered unless it is almost time for the next scheduled dose. They should not take two doses at the same time. The dose is one tablet per day independent of weight and fat mass. Participants will be provided with information about BZA/CE and its potential side effects and contraindications.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants assigned to placebo will receive a daily tablet that matches the BZA/CE to maintain the blind. Placebo tablets, 0.45 mg/20 mg are oval, biconvex, pink tablets, branded with "0.45/20" in black ink on one side. Also to assure the blind is maintain, participants in the placebo group will be given the same instructions for taking the study medication.Tablets should be swallowed whole. If a dose, participants will be instructed to take it as soon as remembered unless it is almost time for the next scheduled dose. They should not take two doses at the same time. The dose is one tablet per day independent of weight and fat mass. Participants will be provided with information about BZA/CE and its potential side effects and contraindications, again to maintain the blind.
intervention type: Drug
intervention name: Bazedoxifene/Conjugated Estrogens (BZA/CE)
description: Daily tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg.
arm group label: Bazedoxifene/Conjugated Estrogens (BZA/CE)
other name: DUAVEE
intervention type: Drug
intervention name: Placebo Oral Tablet
description: Daily placebo tablet
arm group label: Placebo
criteria: 
gender: Female
minimum age: 50 Years
maximum age: 60 Years
healthy volunteers: No
last name: Franck Mauvais-Jarvis, MD
role: Principal Investigator
affiliation: Tulane University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Tulane University Health Sciences Center
investigator full name: Franck Mauvais-Jarvis
investigator title: Professor of Medicine
mesh term: Bazedoxifene
mesh term: Estrogens
mesh term: Estrogens, Conjugated (USP)
sharing ipd: No
ipd description: At this time there is no plan to share individual participant data (IPD)
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 