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Estrogen, Diabetes, and Endothelial Function (EDEN)

Primary Purpose

Type 1 Diabetes

Status
Completed
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Cetrorelix acetate, 0.25 mg/day
Estradiol Patch, 0.025 Mg/24 Hours Weekly Transdermal Film, Extended Release
Placebo patch
Sponsored by
University of Colorado, Denver
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Type 1 Diabetes

Eligibility Criteria

18 Years - 45 Years (Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

  • Premenopausal
  • Euthyroid
  • Not currently planning to become pregnant
  • Not currently breastfeeding
  • No recent history of amenorrhea in the previous 6 months
  • Consent to data and specimen banking
  • No use of hormonal contraceptives

Inclusion Criteria, type 1 diabetes only:

  • Diagnosis of type 1 diabetes for at least 5 years
  • On insulin within a year of diagnosis
  • Current insulin therapy
  • Hemoglobin A1c < 9.5%
  • No macroalbuminuria (AER < 200 ug/min)

Inclusion Criteria, non-diabetic controls only:

  • Hemoglobin A1c < 5.7%

Exclusion Criteria:

  • Pregnant and/or breastfeeding
  • Have not had a menstrual cycle in the last 6 months

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Placebo Comparator

    Arm Label

    GnRHant + E2

    GnRHant + PL

    Arm Description

    Participants in this arm received GnRHant and a transdermal estradiol patch (0.075 mg/day) for a period of 1 week.

    Participants in this arm received GnRHant and a placebo patch for a period of 1 week.

    Outcomes

    Primary Outcome Measures

    Flow-mediated dilation (FMD) at baseline
    FMD will be measured following an intravenous saline infusion and ascorbic acid infusion.
    Flow-mediated dilation (FMD) at follow-up
    FMD will be measured following an intravenous saline infusion and ascorbic acid infusion.
    Change in flow-mediated dilation (FMD)
    FMD will be measured following an intravenous saline infusion and ascorbic acid infusion at baseline and follow-up.
    Quantitative immunuofluorescence of endothelial cell proteins at baseline
    Expression of estrogen receptor alpha, estrogen receptor beta, endothelial nitric oxide synthase, and phosphorylated endothelial nitric oxide synthase in endothelial cells
    Quantitative immunuofluorescence of endothelial cell proteins at follow-up
    Expression of estrogen receptor alpha, estrogen receptor beta, endothelial nitric oxide synthase, and phosphorylated endothelial nitric oxide synthase in endothelial cells
    Change in quantitative immunuofluorescence of endothelial cell proteins
    Expression of estrogen receptor alpha, estrogen receptor beta, endothelial nitric oxide synthase, and phosphorylated endothelial nitric oxide synthase in endothelial cells

    Secondary Outcome Measures

    Full Information

    First Posted
    May 26, 2020
    Last Updated
    June 2, 2020
    Sponsor
    University of Colorado, Denver
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04418908
    Brief Title
    Estrogen, Diabetes, and Endothelial Function
    Acronym
    EDEN
    Official Title
    Vascular Disease, Inflammation and Hormones in Women With Type 1 Diabetes
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2020
    Overall Recruitment Status
    Completed
    Study Start Date
    November 24, 2010 (Actual)
    Primary Completion Date
    October 22, 2018 (Actual)
    Study Completion Date
    October 22, 2018 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    University of Colorado, Denver

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    Yes
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    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.
    Detailed Description
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Type 1 Diabetes

    7. Study Design

    Primary Purpose
    Basic Science
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    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.
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    40 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    GnRHant + E2
    Arm Type
    Active Comparator
    Arm Description
    Participants in this arm received GnRHant and a transdermal estradiol patch (0.075 mg/day) for a period of 1 week.
    Arm Title
    GnRHant + PL
    Arm Type
    Placebo Comparator
    Arm Description
    Participants in this arm received GnRHant and a placebo patch for a period of 1 week.
    Intervention Type
    Drug
    Intervention Name(s)
    Cetrorelix acetate, 0.25 mg/day
    Other Intervention Name(s)
    Cetrotide, GnRHant
    Intervention Description
    All participants self-administered GnRHant daily between the baseline and follow-up visits (cetrorelix acetate, 0.25 mg/day).
    Intervention Type
    Drug
    Intervention Name(s)
    Estradiol Patch, 0.025 Mg/24 Hours Weekly Transdermal Film, Extended Release
    Other Intervention Name(s)
    Climara
    Intervention Description
    Active estradiol transdermal patch.
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo patch
    Intervention Description
    Placebo patch designed to match active Climara patches.
    Primary Outcome Measure Information:
    Title
    Flow-mediated dilation (FMD) at baseline
    Description
    FMD will be measured following an intravenous saline infusion and ascorbic acid infusion.
    Time Frame
    1 week
    Title
    Flow-mediated dilation (FMD) at follow-up
    Description
    FMD will be measured following an intravenous saline infusion and ascorbic acid infusion.
    Time Frame
    1 week
    Title
    Change in flow-mediated dilation (FMD)
    Description
    FMD will be measured following an intravenous saline infusion and ascorbic acid infusion at baseline and follow-up.
    Time Frame
    Baseline and 1 week
    Title
    Quantitative immunuofluorescence of endothelial cell proteins at baseline
    Description
    Expression of estrogen receptor alpha, estrogen receptor beta, endothelial nitric oxide synthase, and phosphorylated endothelial nitric oxide synthase in endothelial cells
    Time Frame
    Baseline
    Title
    Quantitative immunuofluorescence of endothelial cell proteins at follow-up
    Description
    Expression of estrogen receptor alpha, estrogen receptor beta, endothelial nitric oxide synthase, and phosphorylated endothelial nitric oxide synthase in endothelial cells
    Time Frame
    1 week
    Title
    Change in quantitative immunuofluorescence of endothelial cell proteins
    Description
    Expression of estrogen receptor alpha, estrogen receptor beta, endothelial nitric oxide synthase, and phosphorylated endothelial nitric oxide synthase in endothelial cells
    Time Frame
    Baseline and 1 week

    10. Eligibility

    Sex
    Female
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    45 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: Premenopausal Euthyroid Not currently planning to become pregnant Not currently breastfeeding No recent history of amenorrhea in the previous 6 months Consent to data and specimen banking No use of hormonal contraceptives Inclusion Criteria, type 1 diabetes only: Diagnosis of type 1 diabetes for at least 5 years On insulin within a year of diagnosis Current insulin therapy Hemoglobin A1c < 9.5% No macroalbuminuria (AER < 200 ug/min) Inclusion Criteria, non-diabetic controls only: Hemoglobin A1c < 5.7% Exclusion Criteria: Pregnant and/or breastfeeding Have not had a menstrual cycle in the last 6 months
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Janet K Snell-Bergeon, PhD, MPH
    Organizational Affiliation
    University of Colorado, Denver
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

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    Estrogen, Diabetes, and Endothelial Function

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