ClinicalTrials.gg
RecruitingNCT06745466V-RISESUpdated Jul 2, 2026

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

A Phase 4 interventional study of ganirelix acetate in Estrogen and Premenopause, sponsored by University of Delaware. Recruiting at 1 site in United States. Open to female participants aged 40 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-07-02.

Sponsored by University of Delaware · Phase 4, Interventional, and Basic science

From the registry’s dates

  • Started Nov 2024; still recruiting 1 year 11 months later.
Phase
Phase 4
Study type
Interventional
Enrollment
30
Allocation
Non-randomized
Ages
40 Years to 55 Years
Sex
Female
01

Study 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.

Read the detailed description

In the last 20 years, deaths due to cardiovascular disease (CVD) have increased by up to 30% in midlife women. This increase in CVD risk in midlife women is at least partially explained by the declines in estradiol (E2) that occur across the menopausal transition. This loss of E2 induces vascular dysfunction, a major contributor to increased CVD risk. Nevertheless, we have shown that declines in vascular function are evident in some midlife premenopausal women, suggesting that vascular dysfunction-associated CVD risk cannot solely be explained by the loss of E2. Emerging factors that may help explain vascular dysfunction in midlife women include greater emotional vulnerability to daily stressors and poorer sleep health. However, not yet know is the extent to which daily stress and sleep health independently impact vascular function in midlife premenopausal women or the degree to which these associations are influenced by E2. The objective of this project is to test the central hypothesis that (a) greater negative affective responsivity to daily stressors and (b) greater sleep variability will each be related to more severe declines in vascular function in midlife premenopausal women and that these associations will be magnified during E2 suppression (simulated menopause) compared to the follicular phase of the menstrual cycle/placebo phase of hormonal contraception. We will assess affective responsitivy to daily stressors and device-measured sleep characteristics for 10 consecutive days and cutaneous microvascular endothelial function before and during pharmacological E2 suppression.

The investigators will assess multiple dynamic aspects of daily stress processes for 10 consecutive days (mobile app). Investigators will concurrently objectively assess sleep variability (ActiGraph wGT3X). Immediately before and after completion of these ambulatory assessments, Investigators will assess microvascular endothelial function using intradermal microdialysis coupled with laser Doppler flowmetry. Participants will complete two 10-day measurement bursts:The first will occur during the follicular phase of their menstrual cycle or the low hormone/placebo phase of hormonal contraception; The second will occur during supression of endogenous ovarian hormone production via GnRH antagonist ganirelix acetate.

02

Conditions studied

  • Estrogen
  • Premenopause

Keywords

  • Premenopause
  • Estrogen
  • Stress
  • Sleep
  • Vascular function
03

In context

Lead sponsor

University of Delaware is the lead sponsor of 128 studies on the registry; 22 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
40 Years to 55 Years
Sexes eligible
Female
Accepts healthy volunteers
Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Female
  • Age 40-55
  • Premenopausal

Exclusion criteria

Exclusion Criteria:

  • Pregnancy (including a positive urine pregnancy test), planning to become pregnant, or breast-feeding
  • Peri- or
  • Unstable or diagnosed chronic clinical disease, including cardiovascular, metabolic, renal, hepatic, autonomic, , 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)
  • >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 (LARC; e.g., IUDs, birth control implants)
  • Known latex allergy
Terms in these criteria, in plain language(4)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Postmenopausal

Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).

Autoimmune disease

A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.

Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.

BMI (body mass index)

Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.

What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

05

Study design

Phase
Phase 4
Primary purpose
Basic science
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
30 participants (estimated)

Study arms

  • No intervention
    Natural cycle

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

  • Experimental
    No to Low Endogenous Estrogen

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

    Drug: ganirelix acetate

Interventions

  • 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

06

What researchers measure

Primary outcomes

  1. Endothelium-dependent dilation (EDD)

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

    Time frame: Immediately before and after each 10-day measurement burst

  2. Negative affective response to daily stressors

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

    Time frame: 10-day measurement burst

  3. Sleep variability

    Sleep onset standard deviation (minutes) estimated via actigraphy

    Time frame: 10-day measurement burst

07

Study locations

1 of 1 sites recruiting
08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Started Nov 2024 (actual). Primary completion is estimated for Oct 2026, 23 months after the start.

How these figures are worked out, and which studies are left out of them.

Registered
Dec 17, 2024
First posted
Dec 20, 2024
StartActual
Nov 15, 2024
Primary completionEst.
Oct 31, 2026
CompletionEst.
Oct 2027
Last update
Jul 2, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Jul 2, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT06745466
Responsible party
Sponsor
First posted
Dec 20, 2024
Start date
Nov 15, 2024
Primary completion
Oct 31, 2026 (estimated)
Completion
Oct 2027 (estimated)
Last update
Jul 2, 2026

Study contacts

Jody Greaney, PhD
Contact
jgreaney@udel.edu
302-831-2193
Virginia Nuckols, PhD
Contact
gnuckols@udel.edu
Jody Greaney, PhD
principal investigator · University of Delaware

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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Studies of the drug tested here: Ganirelix

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