Ganirelix Acetate for Premenopause

(V-RISES Trial)

Overseen By Virginia Nuckols, PhD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: University of Delaware

Must not be taking: Cardiovascular, Sleep-altering

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

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to examine how the hormone estradiol (E2) affects stress response, sleep patterns, and blood vessel health in premenopausal women. Researchers will compare two groups: one experiencing natural menstrual cycles and another receiving daily injections of ganirelix acetate, a medication that lowers estrogen levels. Premenopausal women who haven't experienced menopause symptoms may be suitable if stress has impacted their sleep or daily life. As a Phase 4 trial, this research involves an FDA-approved treatment, aiming to understand its benefits for more patients.

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 is the safety track record for Ganirelix Acetate?

Research shows that Ganirelix Acetate is generally safe. Most women tolerate it well, with common side effects including mild reactions at the injection site and occasional allergic reactions. Serious side effects are rare.

Other studies have used Ganirelix Acetate in fertility treatments, demonstrating a good safety record. It helps prevent early hormone surges, which is important for managing fertility. Although the treatment is approved for certain uses, each new study provides more insight into its effects in different situations.

For concerns about side effects, consulting a healthcare provider can offer more personalized information. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about Ganirelix Acetate for premenopause because it offers a unique approach compared to traditional hormone therapies. Unlike standard treatments that typically involve hormone replacement, Ganirelix Acetate works by directly blocking the action of certain hormones in the body. This method could potentially provide a more targeted and efficient way to manage symptoms related to hormone fluctuations in premenopausal women. Additionally, its administration through daily injections over a short period might offer faster symptom relief, making it an attractive alternative for those seeking quicker results.

What evidence suggests that Ganirelix Acetate might be an effective treatment for premenopause?

Studies have shown that Ganirelix Acetate effectively prevents early hormone surges during ovarian stimulation treatments. This stabilization of hormone levels benefits fertility treatments. Research indicates that Ganirelix Acetate is safe and generally well-tolerated, with positive results reported. In this trial, participants in the "No to Low Endogenous Estrogen" arm will receive daily Ganirelix Acetate (Antagon) injections for 10 days. This treatment helps maintain hormone balance, which is crucial for managing symptoms and improving health in women before menopause. The treatment has a strong safety record and has proven effective in controlling hormone levels across various conditions. ^{1 2 5 6 7}

Who Is on the Research Team?

Jody Greaney, PhD

Principal Investigator

University of Delaware

Are You a Good Fit for This Trial?

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 have not gone through menopause.

I am between 40 and 55 years old.

Exclusion Criteria

I have a history of gynecological conditions or procedures.

My BMI is over 35.

Suspected potential presence of obstructive sleep apnea (STOP-Bang score >3) or insomnia (Insomnia Severity Index score >15)

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Ganirelix Acetate

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12016398/

Post-marketing safety profile of ganirelix in women Data from clinical trials provide mixed results on the incidence of OHSS with ganirelix. In a European Phase III clinical trial involving ...

2. withpower.com withpower.com/trial/ganirelix-acetate-for-premenopause-2293b

Ganirelix Acetate for Premenopause (V-RISES Trial) Ganirelix Acetate has been shown to effectively prevent premature luteinizing hormone (LH) surges during ovarian stimulation, which is important for fertility ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00725491

A Study to Assess the Efficacy and Safety of Ganirelix ... The primary purpose of this study is to assess that ganirelix is safe and well-tolerated in Chinese women and that a controlled ovarian stimulation (COS) ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0015028204029826

Ganirelix acetate use in normal- and poor-prognosis ... The results have demonstrated that GnRH antagonist use results in acceptable clinical outcomes in normal-prognosis patients. Moreover, we demonstrated that ...

5. academic.oup.com academic.oup.com/humrep/article/15/7/1490/2915322

Treatment with the gonadotrophin-releasing hormone ... The study revealed that a daily dose of 0.25 mg ganirelix prevented LH from rising above 10 IU/l during stimulation, and resulted in a good clinical outcome, ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/99/21057_Antagon_admindocs.pdf

Antagon (ganirelix acetate) 250 ug per 0.5mL injection The safety update also included 11 infant outcomes. Thus a total of more than 280 infant outcomes are known from the development program. For these 280 live ...

7. ema.europa.eu ema.europa.eu/en/documents/rmp/orgalutran-epar-risk-management-plan_en.pdf

risk management plan - European Medicines Agency Evaluation of all safety data and possible risk factors related to ganirelix, revealed hypersensitivity and injection site reactions as important identified ...