<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/NCT03815929</url>
  </required_header>
  <id_info>
    <org_study_id>18-007999</org_study_id>
    <nct_id>NCT03815929</nct_id>
  </id_info>
  <brief_title>Oophorectomy, Estrogen Therapy and Cardiovascular Disease Risk in Young Women</brief_title>
  <official_title>Impact of Individualized Estrogen Therapy on Cardiovascular Disease Risk Parameters in Young Women After Bilateral Oophorectomy: A Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mayo Clinic</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Researchers are trying to assess the appropriate dose of estrogen for decreasing the risk of&#xD;
      cardiovascular disease in women who have removal of their ovaries at a young age, before the&#xD;
      age of 46 years.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Baseline Study Visit: Subjects will report for the Baseline Study Day in an 8 hour fasting&#xD;
      state (water only) and refrain from heavy exercise, caffeine, and alcohol for 24 hours. The&#xD;
      participant will undergo study specific procedures including a urine pregnancy test if they&#xD;
      are of child bearing potential. Participants will also complete a set of questionnaires.&#xD;
      After the completion of the study tests, participants will be offered a meal.&#xD;
&#xD;
      Participants scheduled for surgery to remove their ovaries: after the surgery subjects will&#xD;
      be randomized to one of two groups. They will receive the standard dose of the hormone&#xD;
      (estrogen) patch, generally prescribed to patients after removal both ovaries. Or sent home&#xD;
      on the standard dose hormone patch, hormone levels will be tested every 3-4 weeks, and patch&#xD;
      dose adjusted until the estrogen level is reached that results in the hormone levels of a&#xD;
      young woman before menopause. In order to check hormones, subjects will be able to choose to&#xD;
      have a lab kit sent to them and have the draw done locally, or can come in person.&#xD;
&#xD;
      Participants will also receive a second hormone prescription if they have an intact uterus to&#xD;
      protect the lining of the uterus from the effects of using estrogen alone.&#xD;
&#xD;
      6-Month Study Visit: Subjects will be asked to come back and repeat most of the study&#xD;
      specific tests from the baseline study visit that will take about 5 hours.&#xD;
&#xD;
      1-Year Study Visit: Subjects will be asked to come back for the final visit and will repeat&#xD;
      all the study tests done at baseline visit. This visit will take about 5 hours.&#xD;
&#xD;
      Control Group: Healthy subjects serving as controls to see how measures change over time will&#xD;
      not undergo a surgery or be given estrogen. These healthy subjects will return after the&#xD;
      baseline visit to repeat study visits at 6 and 12-months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 15, 2019</start_date>
  <completion_date type="Anticipated">January 2024</completion_date>
  <primary_completion_date type="Anticipated">January 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Factorial Assignment</intervention_model>
    <intervention_model_description>Subject be placed into three different study arms. Subjects undergoing surgery will be randomized to receive either standard hormone therapy or individualized hormone therapy. These arms will be compared against each other as well as a third arm of healthy timed-control subjects</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Endothelial function</measure>
    <time_frame>Baseline, 6 months, and 12 months</time_frame>
    <description>Brachial artery flow mediated dilation using ultrasonography to measure any endothelium dysfunction occurring over 12 months.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in cerebral vascular reactivity</measure>
    <time_frame>Baseline, 6 months, and 12 months</time_frame>
    <description>Changes to the middle cerebral artery blood flow velocity measured using a Multigon Trans-Cranial Doppler sonogram probe monitoring with three stepwise end-tidal carbon dioxide elevations of constant concentration levels with 3 minutes at each level is compared over planned time frames.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Arterial tonometry</measure>
    <time_frame>Baseline, 6 months, and 12 months</time_frame>
    <description>Arterial stiffness is recorded through high-fidelity pressure waveforms and compared at planned time frames</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in maximal Voluntary Contraction of the non-dominant arm</measure>
    <time_frame>Baseline, 6 months, and 12 months</time_frame>
    <description>Isometric handgrip exercise squeezing a transducer with goal of consistently maintaining a moderate workload average over 5 attempts and compared over time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes to the index of baroreflex sensitivity</measure>
    <time_frame>Baseline, 6 months, and 12 months</time_frame>
    <description>Colder pressor test immersing hand up to wrist in ice water while changes in blood pressure and heart rate are monitored and compared over time frames.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in measurements of whole body and regional fat and fat-free mass</measure>
    <time_frame>Baseline and 12 months</time_frame>
    <description>Measurements will be taken using Dual energy x-ray absorptiometry (DXA) scans and compared over time and between the groups.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">47</enrollment>
  <condition>Cardiovascular Risk Reduction</condition>
  <arm_group>
    <arm_group_label>Standard replacement therapy regimen</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>100 mcg transdermal estradiol patch (or equivalent oral dose)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Titrated replacement therapy regimen</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Transdermal estradiol patch (or equivalent oral dose) titrated to achieve pre-menopausal estradiol level</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Timed Control Group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Healthy age-matched subjects not on hormone therapy</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Estradiol 100 Micrograms Patch</intervention_name>
    <description>Standard</description>
    <arm_group_label>Standard replacement therapy regimen</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Estradiol Patch</intervention_name>
    <description>Individualized</description>
    <arm_group_label>Titrated replacement therapy regimen</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Premenopausal women undergoing (or completion of a) bilateral oophorectomy for&#xD;
             non-malignant diagnoses at Mayo Clinic, Rochester; or premenopausal women not&#xD;
             undergoing the procedure for the timed control group&#xD;
&#xD;
          -  Currently between the ages of 21- 45 years&#xD;
&#xD;
          -  Able to participate fully in all aspects of the study&#xD;
&#xD;
          -  Able to understand and sign the informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of hepatic, renal, or hematological diseases&#xD;
&#xD;
          -  History of venous thromboembolism; peripheral vascular disease; coronary artery&#xD;
             disease; stroke/neurovascular disease&#xD;
&#xD;
          -  Chemotherapy or radiation therapy in the preceding 3 months&#xD;
&#xD;
          -  Current tobacco use&#xD;
&#xD;
          -  Current use of medication that alters autonomic or vascular function (e.g. tricyclic&#xD;
             antidepressants, α-blockers, β-blockers, etc.) or aromatase inhibitor/tamoxifen&#xD;
             therapy&#xD;
&#xD;
          -  Contra-indication to estrogen use&#xD;
&#xD;
          -  Current or previous diagnosis of breast and endometrial cancer&#xD;
&#xD;
          -  For Timed Controls: Are currently pregnant or lactating, or are of child-bearing&#xD;
             potential or are likely to become pregnant during the study and unwilling to use&#xD;
             contraception; Acceptable forms include:Barrier methods (such as a condom or&#xD;
             diaphragm) used with a spermicide (a foam, cream, or gel that kills sperm), Copper&#xD;
             Intra Uterine Device, Hysterectomy, Tubal ligation, Abstinence (no sex)&#xD;
&#xD;
          -  Any condition or factor judged by the investigator to preclude participation in the&#xD;
             study&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ekta Kapoor, MBBS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55902</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.mayo.edu/research/clinical-trials</url>
    <description>Mayo Clinic Clinical Trials</description>
  </link>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>January 17, 2019</study_first_submitted>
  <study_first_submitted_qc>January 23, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 24, 2019</study_first_posted>
  <last_update_submitted>September 5, 2023</last_update_submitted>
  <last_update_submitted_qc>September 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Ekta Kapoor</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Hormone therapy</keyword>
  <keyword>Pre-menopausal Oophorectomy</keyword>
  <keyword>Cardiovascular Disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cardiovascular Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Estradiol 17 beta-cypionate</mesh_term>
    <mesh_term>Estradiol 3-benzoate</mesh_term>
    <mesh_term>Estradiol</mesh_term>
    <mesh_term>Polyestradiol phosphate</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03815929
org study id: 18-007999
nct id: NCT03815929
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Researchers are trying to assess the appropriate dose of estrogen for decreasing the risk of
      cardiovascular disease in women who have removal of their ovaries at a young age, before the
      age of 46 years.
Baseline Study Visit: Subjects will report for the Baseline Study Day in an 8 hour fasting
      state (water only) and refrain from heavy exercise, caffeine, and alcohol for 24 hours. The
      participant will undergo study specific procedures including a urine pregnancy test if they
      are of child bearing potential. Participants will also complete a set of questionnaires.
      After the completion of the study tests, participants will be offered a meal.

      Participants scheduled for surgery to remove their ovaries: after the surgery subjects will
      be randomized to one of two groups. They will receive the standard dose of the hormone
      (estrogen) patch, generally prescribed to patients after removal both ovaries. Or sent home
      on the standard dose hormone patch, hormone levels will be tested every 3-4 weeks, and patch
      dose adjusted until the estrogen level is reached that results in the hormone levels of a
      young woman before menopause. In order to check hormones, subjects will be able to choose to
      have a lab kit sent to them and have the draw done locally, or can come in person.

      Participants will also receive a second hormone prescription if they have an intact uterus to
      protect the lining of the uterus from the effects of using estrogen alone.

      6-Month Study Visit: Subjects will be asked to come back and repeat most of the study
      specific tests from the baseline study visit that will take about 5 hours.

      1-Year Study Visit: Subjects will be asked to come back for the final visit and will repeat
      all the study tests done at baseline visit. This visit will take about 5 hours.

      Control Group: Healthy subjects serving as controls to see how measures change over time will
      not undergo a surgery or be given estrogen. These healthy subjects will return after the
      baseline visit to repeat study visits at 6 and 12-months.
allocation: Randomized
intervention model: Factorial Assignment
intervention model description: Subject be placed into three different study arms. Subjects undergoing surgery will be randomized to receive either standard hormone therapy or individualized hormone therapy. These arms will be compared against each other as well as a third arm of healthy timed-control subjects
primary purpose: Prevention
masking: None (Open Label)
measure: Change in Endothelial function
time frame: Baseline, 6 months, and 12 months
description: Brachial artery flow mediated dilation using ultrasonography to measure any endothelium dysfunction occurring over 12 months.
measure: Change in cerebral vascular reactivity
time frame: Baseline, 6 months, and 12 months
description: Changes to the middle cerebral artery blood flow velocity measured using a Multigon Trans-Cranial Doppler sonogram probe monitoring with three stepwise end-tidal carbon dioxide elevations of constant concentration levels with 3 minutes at each level is compared over planned time frames.
measure: Change in Arterial tonometry
time frame: Baseline, 6 months, and 12 months
description: Arterial stiffness is recorded through high-fidelity pressure waveforms and compared at planned time frames
measure: Changes in maximal Voluntary Contraction of the non-dominant arm
time frame: Baseline, 6 months, and 12 months
description: Isometric handgrip exercise squeezing a transducer with goal of consistently maintaining a moderate workload average over 5 attempts and compared over time.
measure: Changes to the index of baroreflex sensitivity
time frame: Baseline, 6 months, and 12 months
description: Colder pressor test immersing hand up to wrist in ice water while changes in blood pressure and heart rate are monitored and compared over time frames.
measure: Changes in measurements of whole body and regional fat and fat-free mass
time frame: Baseline and 12 months
description: Measurements will be taken using Dual energy x-ray absorptiometry (DXA) scans and compared over time and between the groups.
arm group label: Standard replacement therapy regimen
arm group type: Active Comparator
description: 100 mcg transdermal estradiol patch (or equivalent oral dose)
arm group label: Titrated replacement therapy regimen
arm group type: Active Comparator
description: Transdermal estradiol patch (or equivalent oral dose) titrated to achieve pre-menopausal estradiol level
arm group label: Timed Control Group
arm group type: No Intervention
description: Healthy age-matched subjects not on hormone therapy
intervention type: Drug
intervention name: Estradiol 100 Micrograms Patch
description: Standard
arm group label: Standard replacement therapy regimen
intervention type: Drug
intervention name: Estradiol Patch
description: Individualized
arm group label: Titrated replacement therapy regimen
criteria: 
gender: Female
minimum age: 21 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ekta Kapoor, MBBS
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
country: United States
url: https://www.mayo.edu/research/clinical-trials
description: Mayo Clinic Clinical Trials
responsible party type: Principal Investigator
investigator affiliation: Mayo Clinic
investigator full name: Ekta Kapoor
investigator title: Principal Investigator
mesh term: Cardiovascular Diseases
mesh term: Estradiol 17 beta-cypionate
mesh term: Estradiol 3-benzoate
mesh term: Estradiol
mesh term: Polyestradiol phosphate