EstrogenPhase 4V-RISESNCT06745466
Disentangling the Effects of Daily Stress, Sleep, and Sex Hormones on Accelerated Vascular Aging in Midlife Women
A Phase 4 study testing ganirelix acetate in people with Estrogen and Premenopause, run by University of Delaware at 1 site in United States.
Trial 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 more about this study
- Who is it for?
- Ages 40 to 55 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Estrogen, Premenopause
- What is being tested?
- ganirelix acetate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Nov 2024to Oct 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 55 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Female
- Age 40-55
- Premenopausal
Who cannot join
- 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)
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Virginia Nuckols, PhD contact
United States1 site, 1 recruiting
- Recruiting
University of Delaware
Newark, Delaware, 19713
Jody Greaney, PhD, 302-831-2193, jgreaney@udel.edu
Virginia Nuckols, PhD, gnuckols@udel.edu
About this study
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.
- Conditions
- Estrogen, Premenopause
- Being tested
- ganirelix acetate
- Keywords
- Premenopause, Estrogen, Stress, Sleep, Vascular function
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ganirelix acetateDrug
Also called Antagon
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: ganirelix acetate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Endothelium-dependent dilation (EDD)
EDD will be calculated as the area under the dose-response curve (AUC) to ascending concentrations of acetylcholine.
Measured: 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
Measured: 10-day measurement burst
Sleep variability
Sleep onset standard deviation (minutes) estimated via actigraphy
Measured: 10-day measurement burst
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2024
- Study start15 Nov 2024
- Primary completion31 Oct 2026 (estimated)
- Study completionOct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EstrogenStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Delaware
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Jody Greaney, PhD, Principal investigator, University of Delaware
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06745466
- Sponsor's protocol ID
- 2207199
- Other IDs
- R21AG090810
- Acronym
- V-RISES
- Status last verified
- Apr 2026
- First submitted
- 17 Dec 2024
- Last updated
- 2 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Disentangling the Effects of Daily Stress, Sleep, and Sex Hormones on Accelerated Vascular Aging in Midlife Women
- ClinicalTrials.gov ID
- NCT06745466
- Acronym / sponsor ID
- V-RISES / 2207199
- Conditions
- Estrogen, Premenopause
- Keywords
- Premenopause, Estrogen, Stress, Sleep, Vascular function
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University of DelawareUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 15 Nov 2024 (actual)
- Primary completion
- 31 Oct 2026 (estimated)
- Study completion
- Oct 2027 (estimated)
- First posted
- 20 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Natural cycle | No intervention | –Participants will undergo study measurements during the follicular phase of their natural menstrual cycle. |
| No to Low Endogenous Estrogen | Experimental | Drug: ganirelix acetateParticipants will undergo study measurements during 10 days of daily ganirelix acetate (Antagon) injections. |
Who may qualify
- Ages
- 40 to 55 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Female
- Age 40-55
- Premenopausal
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ganirelix acetateAlso: AntagonGanirelix 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. | Drug | No to Low Endogenous Estrogen |
Primary outcome
Endothelium-dependent dilation (EDD)
Time frame: Immediately before and after each 10-day measurement burst
EDD will be calculated as the area under the dose-response curve (AUC) to ascending concentrations of acetylcholine.
Negative affective response to daily stressors
Time frame: 10-day measurement burst
Within-person composite slope between daily stressors and daily negative affect
Sleep variability
Time frame: 10-day measurement burst
Sleep onset standard deviation (minutes) estimated via actigraphy
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Virginia Nuckols, PhD contact
Jody Greaney, PhD principal investigator
University of Delaware
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing ganirelix acetate in people with Estrogen and Premenopause, run by University of Delaware at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jody Greaney, PhD (302-831-2193, jgreaney@udel.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Endothelium-dependent dilation (EDD) (time frame: Immediately before and after each 10-day measurement burst). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2026.