<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/NCT04418908</url>
  </required_header>
  <id_info>
    <org_study_id>10-0591</org_study_id>
    <nct_id>NCT04418908</nct_id>
  </id_info>
  <brief_title>Estrogen, Diabetes, and Endothelial Function</brief_title>
  <acronym>EDEN</acronym>
  <official_title>Vascular Disease, Inflammation and Hormones in Women With Type 1 Diabetes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Colorado, Denver</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Colorado, Denver</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study planned to learn more about women and how the drop in estradiol levels during&#xD;
      menopause may affect their cardiovascular risk. With aging, the arteries that are located&#xD;
      around the heart get stiffer, and this increase in arterial stiffness can lead to a number of&#xD;
      health problems such as high blood pressure and heart disease. In this study, the&#xD;
      investigators examined whether a short-term drop in estrogen levels caused arteries to become&#xD;
      stiffer, and explored potential reasons for stiffening arteries.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Participants completed two study visits. The baseline study visit occurred during the early&#xD;
      follicular phase of the menstrual cycle, confirmed via take-home ovulation testing. On the&#xD;
      day of the baseline study visit, all participants underwent ovarian sex hormone suppression&#xD;
      with GnRHant therapy (cetrorelix acetate, 0.25 mg/day) delivered daily as subcutaneous&#xD;
      injections for a 1-week period. Participants were randomized to one of two concurrent&#xD;
      intervention groups: transdermal estradiol patch (0.075 mg/day) (+E2) or placebo patch (+PL)&#xD;
      and returned for a follow-up visit after 1 week of the intervention. Both study visits&#xD;
      included collection of anthropometric measures, a fasting blood sample, measures of arterial&#xD;
      stiffness, flow-mediated dilation, and endothelial cells via an intravenous catheter.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 24, 2010</start_date>
  <completion_date type="Actual">October 22, 2018</completion_date>
  <primary_completion_date type="Actual">October 22, 2018</primary_completion_date>
  <phase>N/A</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>
    <intervention_model_description>Participants were randomized to either receiving a gonadotropin-releasing antagonist (GnRHant) with estradiol add-back (+E2) or placebo (+PL). Investigators and participants were blinded to randomization status until the study was completed.</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Flow-mediated dilation (FMD) at baseline</measure>
    <time_frame>1 week</time_frame>
    <description>FMD will be measured following an intravenous saline infusion and ascorbic acid infusion.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Flow-mediated dilation (FMD) at follow-up</measure>
    <time_frame>1 week</time_frame>
    <description>FMD will be measured following an intravenous saline infusion and ascorbic acid infusion.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in flow-mediated dilation (FMD)</measure>
    <time_frame>Baseline and 1 week</time_frame>
    <description>FMD will be measured following an intravenous saline infusion and ascorbic acid infusion at baseline and follow-up.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Quantitative immunuofluorescence of endothelial cell proteins at baseline</measure>
    <time_frame>Baseline</time_frame>
    <description>Expression of estrogen receptor alpha, estrogen receptor beta, endothelial nitric oxide synthase, and phosphorylated endothelial nitric oxide synthase in endothelial cells</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Quantitative immunuofluorescence of endothelial cell proteins at follow-up</measure>
    <time_frame>1 week</time_frame>
    <description>Expression of estrogen receptor alpha, estrogen receptor beta, endothelial nitric oxide synthase, and phosphorylated endothelial nitric oxide synthase in endothelial cells</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in quantitative immunuofluorescence of endothelial cell proteins</measure>
    <time_frame>Baseline and 1 week</time_frame>
    <description>Expression of estrogen receptor alpha, estrogen receptor beta, endothelial nitric oxide synthase, and phosphorylated endothelial nitric oxide synthase in endothelial cells</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Type 1 Diabetes</condition>
  <arm_group>
    <arm_group_label>GnRHant + E2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants in this arm received GnRHant and a transdermal estradiol patch (0.075 mg/day) for a period of 1 week.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GnRHant + PL</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants in this arm received GnRHant and a placebo patch for a period of 1 week.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cetrorelix acetate, 0.25 mg/day</intervention_name>
    <description>All participants self-administered GnRHant daily between the baseline and follow-up visits (cetrorelix acetate, 0.25 mg/day).</description>
    <arm_group_label>GnRHant + E2</arm_group_label>
    <arm_group_label>GnRHant + PL</arm_group_label>
    <other_name>Cetrotide</other_name>
    <other_name>GnRHant</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Estradiol Patch, 0.025 Mg/24 Hours Weekly Transdermal Film, Extended Release</intervention_name>
    <description>Active estradiol transdermal patch.</description>
    <arm_group_label>GnRHant + E2</arm_group_label>
    <other_name>Climara</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo patch</intervention_name>
    <description>Placebo patch designed to match active Climara patches.</description>
    <arm_group_label>GnRHant + PL</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Premenopausal&#xD;
&#xD;
          -  Euthyroid&#xD;
&#xD;
          -  Not currently planning to become pregnant&#xD;
&#xD;
          -  Not currently breastfeeding&#xD;
&#xD;
          -  No recent history of amenorrhea in the previous 6 months&#xD;
&#xD;
          -  Consent to data and specimen banking&#xD;
&#xD;
          -  No use of hormonal contraceptives&#xD;
&#xD;
        Inclusion Criteria, type 1 diabetes only:&#xD;
&#xD;
          -  Diagnosis of type 1 diabetes for at least 5 years&#xD;
&#xD;
          -  On insulin within a year of diagnosis&#xD;
&#xD;
          -  Current insulin therapy&#xD;
&#xD;
          -  Hemoglobin A1c &lt; 9.5%&#xD;
&#xD;
          -  No macroalbuminuria (AER &lt; 200 ug/min)&#xD;
&#xD;
        Inclusion Criteria, non-diabetic controls only:&#xD;
&#xD;
          -  Hemoglobin A1c &lt; 5.7%&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant and/or breastfeeding&#xD;
&#xD;
          -  Have not had a menstrual cycle in the last 6 months&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Janet K Snell-Bergeon, PhD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Colorado, Denver</affiliation>
  </overall_official>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>May 26, 2020</study_first_submitted>
  <study_first_submitted_qc>June 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 5, 2020</study_first_posted>
  <last_update_submitted>June 2, 2020</last_update_submitted>
  <last_update_submitted_qc>June 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 5, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 1</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cetrorelix</mesh_term>
    <mesh_term>Estradiol</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/NCT04418908
org study id: 10-0591
nct id: NCT04418908
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: Yes
This study planned to learn more about women and how the drop in estradiol levels during
      menopause may affect their cardiovascular risk. With aging, the arteries that are located
      around the heart get stiffer, and this increase in arterial stiffness can lead to a number of
      health problems such as high blood pressure and heart disease. In this study, the
      investigators examined whether a short-term drop in estrogen levels caused arteries to become
      stiffer, and explored potential reasons for stiffening arteries.
Participants completed two study visits. The baseline study visit occurred during the early
      follicular phase of the menstrual cycle, confirmed via take-home ovulation testing. On the
      day of the baseline study visit, all participants underwent ovarian sex hormone suppression
      with GnRHant therapy (cetrorelix acetate, 0.25 mg/day) delivered daily as subcutaneous
      injections for a 1-week period. Participants were randomized to one of two concurrent
      intervention groups: transdermal estradiol patch (0.075 mg/day) (+E2) or placebo patch (+PL)
      and returned for a follow-up visit after 1 week of the intervention. Both study visits
      included collection of anthropometric measures, a fasting blood sample, measures of arterial
      stiffness, flow-mediated dilation, and endothelial cells via an intravenous catheter.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Participants were randomized to either receiving a gonadotropin-releasing antagonist (GnRHant) with estradiol add-back (+E2) or placebo (+PL). Investigators and participants were blinded to randomization status until the study was completed.
primary purpose: Basic Science
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Flow-mediated dilation (FMD) at baseline
time frame: 1 week
description: FMD will be measured following an intravenous saline infusion and ascorbic acid infusion.
measure: Flow-mediated dilation (FMD) at follow-up
time frame: 1 week
description: FMD will be measured following an intravenous saline infusion and ascorbic acid infusion.
measure: Change in flow-mediated dilation (FMD)
time frame: Baseline and 1 week
description: FMD will be measured following an intravenous saline infusion and ascorbic acid infusion at baseline and follow-up.
measure: Quantitative immunuofluorescence of endothelial cell proteins at baseline
time frame: Baseline
description: Expression of estrogen receptor alpha, estrogen receptor beta, endothelial nitric oxide synthase, and phosphorylated endothelial nitric oxide synthase in endothelial cells
measure: Quantitative immunuofluorescence of endothelial cell proteins at follow-up
time frame: 1 week
description: Expression of estrogen receptor alpha, estrogen receptor beta, endothelial nitric oxide synthase, and phosphorylated endothelial nitric oxide synthase in endothelial cells
measure: Change in quantitative immunuofluorescence of endothelial cell proteins
time frame: Baseline and 1 week
description: Expression of estrogen receptor alpha, estrogen receptor beta, endothelial nitric oxide synthase, and phosphorylated endothelial nitric oxide synthase in endothelial cells
arm group label: GnRHant + E2
arm group type: Active Comparator
description: Participants in this arm received GnRHant and a transdermal estradiol patch (0.075 mg/day) for a period of 1 week.
arm group label: GnRHant + PL
arm group type: Placebo Comparator
description: Participants in this arm received GnRHant and a placebo patch for a period of 1 week.
intervention type: Drug
intervention name: Cetrorelix acetate, 0.25 mg/day
description: All participants self-administered GnRHant daily between the baseline and follow-up visits (cetrorelix acetate, 0.25 mg/day).
arm group label: GnRHant + E2
arm group label: GnRHant + PL
other name: Cetrotide
other name: GnRHant
intervention type: Drug
intervention name: Estradiol Patch, 0.025 Mg/24 Hours Weekly Transdermal Film, Extended Release
description: Active estradiol transdermal patch.
arm group label: GnRHant + E2
other name: Climara
intervention type: Drug
intervention name: Placebo patch
description: Placebo patch designed to match active Climara patches.
arm group label: GnRHant + PL
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Janet K Snell-Bergeon, PhD, MPH
role: Principal Investigator
affiliation: University of Colorado, Denver
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 1
mesh term: Cetrorelix
mesh term: Estradiol