Estrogen, Diabetes, and Endothelial Function

NCT04418908 | Completed

• 1 other identifier: 10-0591
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Type 1 Diabetes

Outcome Measures

Primary Outcomes (6)

• Flow-mediated dilation (FMD) at baseline

  FMD will be measured following an intravenous saline infusion and ascorbic acid infusion.

  1 week

• Flow-mediated dilation (FMD) at follow-up

  FMD will be measured following an intravenous saline infusion and ascorbic acid infusion.

  1 week

• Change in flow-mediated dilation (FMD)

  FMD will be measured following an intravenous saline infusion and ascorbic acid infusion at baseline and follow-up.

  Baseline and 1 week

• 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

  Baseline

• 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

  1 week

• 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

  Baseline and 1 week

Study Arms (2)

GnRHant + E2

ACTIVE COMPARATOR

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

Drug: Cetrorelix acetate, 0.25 mg/day; Drug: Estradiol Patch, 0.025 Mg/24 Hours Weekly Transdermal Film, Extended Release

GnRHant + PL

PLACEBO COMPARATOR

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

Drug: Cetrorelix acetate, 0.25 mg/day; Drug: Placebo patch

Interventions

Cetrorelix acetate, 0.25 mg/day DRUG

All participants self-administered GnRHant daily between the baseline and follow-up visits (cetrorelix acetate, 0.25 mg/day).

Also known as: Cetrotide, GnRHant

GnRHant + E2; GnRHant + PL

Estradiol Patch, 0.025 Mg/24 Hours Weekly Transdermal Film, Extended Release DRUG

Active estradiol transdermal patch.

Also known as: Climara

GnRHant + E2

Placebo patch DRUG

Placebo patch designed to match active Climara patches.

GnRHant + PL

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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)
• Hemoglobin A1c \< 5.7%

You may not qualify if:

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

Sponsors & Collaborators

• University of Colorado, Denver: lead

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

cetrorelix; LHRH, N-acetyl-(4-chlorophenylalanyl)(1)-(4-chlorophenylalanyl)(2)-tryptophyl(3)-arginyl(6)-alanine(10)-; Estradiol

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Janet K Snell-Bergeon, PhD, MPH

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 26, 2020
• First Posted: June 5, 2020
• Study Start: November 24, 2010
• Primary Completion: October 22, 2018
• Study Completion: October 22, 2018
• Last Updated: June 5, 2020

Record last verified: 2020-06