Disentangling the Effects of Daily Stress, Sleep, and Sex Hormones on Accelerated Vascular Aging in Midlife Women

NCT06745466 | Recruiting Phase 4 FDA Drug

• 2 other identifiers: 2207199R21AG090810
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to identify the impact of estradiol (E2) on the associations between (a) responsivity to daily stress or (b) sleep variability with vascular function in midlife premenopausal women.

Conditions

Estrogen; Premenopause

Keywords

Premenopause; Estrogen; Stress; Sleep; Vascular function

Outcome Measures

Primary Outcomes (3)

• Endothelium-dependent dilation (EDD)

  EDD will be calculated as the area under the dose-response curve (AUC) to ascending concentrations of acetylcholine.

  Immediately before and after each 10-day measurement burst

• Negative affective response to daily stressors

  Within-person composite slope between daily stressors and daily negative affect

  10-day measurement burst

• Sleep variability

  Sleep onset standard deviation (minutes) estimated via actigraphy

  10-day measurement burst

Study Arms (2)

Natural cycle

NO INTERVENTION

Participants will undergo study measurements during the follicular phase of their natural menstrual cycle.

No to Low Endogenous Estrogen

EXPERIMENTAL

Participants will undergo study measurements during 10 days of daily ganirelix acetate (Antagon) injections.

Drug: ganirelix acetate

Interventions

ganirelix acetate DRUG

Ganirelix acetate (Antagon) will be used to prevent endogenous production of ovarian hormones in young women. Ganirelix is derived from native GnRH, and acts by competitively blocking GnRH receptors on the pituitary and subsequent pathways. Thus, administration of the GnRH antagonist (GnRHant) suppresses steroidogenesis, leading to low or undetectable serum estrogen and progesterone concentrations, which occurs within two days of initiation of administration. Women will self-administer subcutaneous injections (0.25 mg/day in 0.5 ml of normal saline) of the GnRH antagonist ganirelix acetate (Antagon, Organon, Inc., West Orange, New Jersey,) every day for \~12-15 days (starting on day \~2-4 of the menstrual cycle). Testing will occur on day 3-4 and day14-15 of using Antagon.

Also known as: Antagon

No to Low Endogenous Estrogen

Eligibility Criteria

• Age: 40 Years - 55 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Female
• Age 40-55
• Premenopausal

You may not qualify if:

• Pregnancy (including a positive urine pregnancy test), planning to become pregnant, or breast-feeding
• Peri- or post-menopausal
• Unstable or diagnosed chronic clinical disease, including cardiovascular, metabolic, renal, hepatic, autonomic, autoimmune, or dermatological disease
• Current or lifetime major psychiatric illness (e.g., major depressive disorder, bipolar disorder, schizophrenia, eating disorders)
• History of hysterectomy (complete or partial), polycystic ovary syndrome, endometrial hyperplasia, irregular menstrual cycles, or endometrial ablation
• Suspected potential presence of obstructive sleep apnea (STOP-Bang score \>3) or insomnia (Insomnia Severity Index score \>15)
• Current or recent (within 8 wks) use of medications that could conceivably alter cardiovascular function or sleep health
• Changes or alterations in medication status (starting a new, additional, or different medication or changing the dose of a current medication)
• Body mass index \>35 kg/m2
• Tobacco or nicotine use, including vaping and electronic cigarettes
• Working night-time or rotating shift work within the previous 3 months
• Trans-meridian travel during study enrollment (inclusive of the entire duration of enrollment and the period between testing cycles)
• Known allergies to pharmacological agents/drugs
• Current use of long-acting reversible contraception (LARC; e.g., IUDs, birth control implants)
• Known latex allergy

Sponsors & Collaborators

• University of Delaware: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

University of Delaware

Newark, Delaware, 19713, United States

RECRUITING

MeSH Terms

Interventions

ganirelix

Study Officials

• Jody Greaney, PhD

  University of Delaware

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jody Greaney, PhD

CONTACT

302-831-3181; jgreaney@udel.edu

Virginia Nuckols, PhD

CONTACT

gnuckols@udel.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2024
• First Posted: December 20, 2024
• Study Start: November 15, 2024
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 1, 2027
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)