Ganirelix Acetate for Premenopause

(V-RISES Trial)

Overseen by Jody Greaney, PhD

Age: 18 - 65

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: University of Delaware

Must not be taking: Cardiovascular, Sleep-altering

Disqualifiers: Pregnancy, Cardiovascular disease, Psychiatric illness, Obstructive sleep apnea, others

No Placebo Group

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that you have not used medications that could affect cardiovascular function or sleep health in the past 8 weeks, and you cannot change your medication status during the study. This means you may need to stop certain medications before joining the trial.

What data supports the effectiveness of the drug Ganirelix Acetate for premenopause?

Ganirelix Acetate has been shown to effectively prevent premature luteinizing hormone (LH) surges during ovarian stimulation, which is important for fertility treatments. In studies, it has been well tolerated and resulted in a good pregnancy rate in women undergoing in vitro fertilization. ^{1 2 3 4 5}

How does the drug ganirelix acetate differ from other treatments for premenopause?

Ganirelix acetate is unique because it is a gonadotropin-releasing hormone (GnRH) antagonist that works by blocking GnRH receptors, preventing the release of hormones that stimulate the ovaries. This drug is administered via subcutaneous injection and is known for its ability to prevent premature hormone surges, which is different from other treatments that may not specifically target hormone regulation in this way. ^{1 2 3 5 6}

Research Team

Jody Greaney, PhD

Principal Investigator

University of Delaware

Eligibility Criteria

This trial is for midlife premenopausal women who are interested in understanding how their estrogen levels might affect their body's response to daily stress and sleep patterns, particularly concerning the health of their blood vessels.

Inclusion Criteria

I am female.

I am between 40 and 55 years old.

I have not gone through menopause.

Exclusion Criteria

I have a history of gynecological conditions or procedures.

My BMI is over 35.

Pregnancy (including a positive urine pregnancy test), planning to become pregnant, or breast-feeding

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Measurement Burst 1

Participants undergo study measurements during the follicular phase of their menstrual cycle or the low hormone/placebo phase of hormonal contraception. This includes assessing daily stress processes and sleep variability for 10 consecutive days.

10 days

Daily assessments (remote)

Measurement Burst 2

Participants undergo study measurements during suppression of endogenous ovarian hormone production via GnRH antagonist ganirelix acetate. This includes assessing daily stress processes and sleep variability for 10 consecutive days.

10 days

Daily assessments (remote)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Ganirelix Acetate (Hormone Therapy)

Trial Overview The study is testing the effects of a medication called ganirelix acetate on how estradiol (a form of estrogen) influences the relationship between daily stress, sleep variability, and vascular function in these women.

Participant Groups

Group I: No to Low Endogenous Estrogen Experimental Treatment 1 Intervention

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

Group II: Natural cycle Active Control 1 Intervention

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

Who Is Running the Clinical Trial?

University of Delaware

Lead Sponsor

Trials

167

Recruited

25,700+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Findings from Research

Ganirelix, a GnRH antagonist, significantly decreased LH levels during ovarian stimulation in normally cycling women, but it also prevented normal follicle maturation, as evidenced by the lack of ovulation in 8 out of 10 participants during treatment.

The study indicates that ganirelix interferes with the process of dominant follicle selection in the ovaries, leading to delayed ovulation and reduced follicle growth compared to the control cycle.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of a GnRH antagonist on follicle maturation in normal women. Pousias, S., Messini, CI., Anifandis, G., et al.[2020]

Ganirelix, a gonadotrophin-releasing hormone antagonist, significantly reduces the treatment period for controlled ovarian hyperstimulation in assisted reproduction compared to traditional agonists like buserelin, leuprolide, and triptorelin.

The safety and tolerance of ganirelix are good, and it shows favorable overall clinical outcomes, making it a convenient option for clinicians and patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The gonadotrophin-releasing hormone antagonist ganirelix--history and introductory data. Out, HJ., Mannaerts, BM.[2019]

A study involving 16 healthy females demonstrated that administering ganirelix, a GnRH antagonist, via a needle-free Medi-Jector device is as effective as traditional needle injections, showing similar pharmacokinetics and local tolerance.

The use of ganirelix significantly suppressed luteinizing hormone and follicle-stimulating hormone levels, indicating its potential for long-term treatment of sex-steroid-dependent disorders without major side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local tolerance, pharmacokinetics, and dynamics of ganirelix (Orgalutran) administration by Medi-Jector compared to conventional needle injections. Oberyé, J., Mannaerts, B., Huisman, J., et al.[2019]

In a Phase III trial involving 313 women undergoing controlled ovarian hyperstimulation, ganirelix acetate was found to be effective and well tolerated for preventing premature LH surges, with similar pregnancy rates compared to leuprolide acetate.

Ganirelix resulted in fewer moderate and severe injection site reactions (11.9% and 0.6%) compared to leuprolide (24.4% and 1.1%), indicating better local tolerance and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ganirelix acetate versus leuprolide acetate in women undergoing controlled ovarian hyperstimulation. Fluker, M., Grifo, J., Leader, A., et al.[2019]

Ganirelix is an effective GnRH antagonist that prevents premature LH surges during controlled ovarian stimulation, leading to a pregnancy rate of 40.3% per embryo transfer in women undergoing in vitro fertilization.

The drug is generally well tolerated, with common side effects including local injection site reactions, nausea, and fatigue, indicating a favorable safety profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ganirelix. Gillies, PS., Faulds, D., Balfour, JA., et al.[2018]

In a study involving 47 patients at high risk for ovarian hyperstimulation syndrome, treatment with ganirelix acetate led to a significant reduction in serum E2 levels by approximately 49.5% for long-luteal and 41.0% for microdose flare regimens.

The treatment resulted in a pregnancy rate of 68.1%, indicating that ganirelix acetate is effective in managing high E2 levels while still allowing for gonadotropin use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment with gonadotropin-releasing hormone (GnRH) antagonists in women suppressed with GnRH agonist may avoid cycle cancellation in patients at risk for ovarian hyperstimulation syndrome. Gustofson, RL., Larsen, FW., Bush, MR., et al.[2016]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

The effect of a GnRH antagonist on follicle maturation in normal women. [2020]

2. England pubmed.ncbi.nlm.nih.gov

The gonadotrophin-releasing hormone antagonist ganirelix--history and introductory data. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Local tolerance, pharmacokinetics, and dynamics of ganirelix (Orgalutran) administration by Medi-Jector compared to conventional needle injections. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ganirelix acetate versus leuprolide acetate in women undergoing controlled ovarian hyperstimulation. [2019]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Ganirelix. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Treatment with gonadotropin-releasing hormone (GnRH) antagonists in women suppressed with GnRH agonist may avoid cycle cancellation in patients at risk for ovarian hyperstimulation syndrome. [2016]