Clinical trial NCT04418908: Estrogen, Diabetes, and Endothelial Function
Official title: Vascular Disease, Inflammation and Hormones in Women With Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetes
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2020-06-05
Enrollment: 40
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
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

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.

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

Primary outcomes:
measure: Flow-mediated dilation (FMD) at baseline
timeFrame: 1 week
measure: Flow-mediated dilation (FMD) at follow-up
timeFrame: 1 week
measure: Change in flow-mediated dilation (FMD)
timeFrame: Baseline and 1 week
measure: Quantitative immunuofluorescence of endothelial cell proteins at baseline
timeFrame: Baseline
measure: Quantitative immunuofluorescence of endothelial cell proteins at follow-up
timeFrame: 1 week
measure: Change in quantitative immunuofluorescence of endothelial cell proteins
timeFrame: Baseline and 1 week
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: University of Colorado, Denver
name: Janet K Snell-Bergeon, PhD, MPH
role: PRINCIPAL_INVESTIGATOR
References: