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
About this trial
This is an interventional basic science trial for Type 1 Diabetes
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
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
NCT ID
NCT04418908
First Posted
May 26, 2020
Last Updated
June 2, 2020
Sponsor
University of Colorado, Denver
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
Learn more about this trial
Estrogen, Diabetes, and Endothelial Function
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