Kisspeptin for Reproductive Disorders

Overseen By Yee-Ming Chan, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Massachusetts General Hospital

Must be taking: Hormone therapy

Must not be taking: Prescription medications

Disqualifiers: Chronic diseases, Illicit drug use, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4-6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how the hormone kisspeptin affects the reproductive system by examining its ability to trigger the release of other important hormones. Participants will receive either kisspeptin or another hormone, GnRH (gonadotropin-releasing hormone), through an injection. Healthy men, women, and postmenopausal women without chronic diseases or current medications may qualify, as well as individuals with certain reproductive disorders like polycystic ovarian syndrome (PCOS) or hypogonadism, a condition where the body produces little or no sex hormones. The study seeks insights that could lead to new treatments for reproductive issues. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop taking my current medications for the trial?

Yes, you will need to stop taking most prescription medications for at least 2 months before the trial, except for seasonal allergy medications, hormone replacement therapy, and medications used to treat your reproductive condition. If you are on hormone therapy, you may need to undergo a washout period (time without taking certain medications).

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that kisspeptin, a hormone naturally found in the body, is safe for humans. Studies have not identified any major side effects from its use. Animal research also supports its safety, as even high doses did not cause problems. GnRH, another hormone, has been well-researched and used in various treatments. It is generally safe but can affect pregnancy outcomes, requiring caution in certain cases. Overall, past research indicates that both treatments in this study have been well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about kisspeptin 112-121 for reproductive disorders because it offers a new way to stimulate hormone release. Unlike traditional treatments that mainly involve synthetic hormones like GnRH agonists or antagonists, kisspeptin works by naturally activating the release of GnRH from the brain. This innovative approach could lead to more precise control of reproductive hormones with potentially fewer side effects. Additionally, the option to administer kisspeptin both intravenously and subcutaneously provides flexibility in treatment, which could make it more convenient for patients.

What evidence suggests that this trial's treatments could be effective for reproductive disorders?

This trial will evaluate the effects of kisspeptin and GnRH on reproductive disorders. Research has shown that kisspeptin plays a crucial role in controlling the reproductive system by releasing other key hormones, such as GnRH, which manage reproduction. Studies have found that kisspeptin is essential for normal puberty and adult reproductive health. GnRH regulates the reproductive hormone cycle and has helped treat conditions like endometrial hyperplasia. In this trial, participants will receive either kisspeptin, GnRH, or both, to explore their potential in addressing reproductive disorders by balancing hormone levels. ^{1 2 6 7 8}

Who Is on the Research Team?

Stephanie B Seminara, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for healthy men (21-40) with normal sexual function, women (21-40) with regular menstrual cycles, postmenopausal women (50-60), and individuals diagnosed with reproductive disorders like PCOS or hypogonadotropic hypogonadism. Participants should not have chronic diseases, a history of severe medication reactions, or excessive substance use.

Inclusion Criteria

People with problems related to their ability to have children.

I am a healthy woman aged 50-60, postmenopausal, and tested negative for Factor V Leiden if needed.

People who are in good health.

Exclusion Criteria

I have a reproductive disorder and have had a severe medication reaction or a confirmed pituitary tumor.

You are a healthy person who had a serious reaction to a medication in the past.

I am a healthy postmenopausal woman with high androgen levels, unable to stop hormone therapy if needed.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous (IV) or subcutaneous (SC) administration of kisspeptin and/or GnRH to study their effects on reproductive hormone secretion

4-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• GnRH
• kisspeptin 112-121

Trial Overview The study investigates the effects of kisspeptin on the reproductive system by administering it to participants. Kisspeptin is known to trigger hormone release including GnRH which plays a key role in reproduction.

How Is the Trial Designed?

Group I: kisspeptin, GnRH Experimental Treatment 2 Interventions

Intravenous (IV) or subcutaneous (SC) administration of kisspeptin 112-121 and/or administration of GnRH

GnRH is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Gonadorelin for:

• Infertility
• Precocious puberty
• Endometriosis
• Prostate cancer

Approved in European Union as Gonadorelin for:

• Infertility
• Precocious puberty
• Endometriosis
• Prostate cancer
• Breast cancer

Approved in Canada as Gonadorelin for:

• Infertility
• Precocious puberty
• Endometriosis
• Prostate cancer

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Published Research Related to This Trial

Metastin, a peptide linked to the GPR54 receptor, plays a role in regulating reproductive functions and is found in higher levels in pregnant women, suggesting its importance in reproductive health.

In a patient with isolated hypogonadotropic hypogonadism, high levels of luteinizing hormone releasing hormone (LHRH) were observed, but plasma metastin levels were normal, indicating that peripheral metastin may have different functions compared to its central role in stimulating reproductive hormone release.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Establishment and clinical application of enzyme immunoassays for determination of luteinizing hormone releasing hormone and metastin. Katagiri, F., Tomita, K., Oishi, S., et al.[2011]

GnRH analogues are established as safe and effective treatments for hormone-dependent advanced prostate cancer, but their unique mechanism of action complicates the entry of generic versions into the market.

Regulatory requirements for GnRH analogues are stringent due to their comparison with surgical castration, which has a 100% success rate, and they face competition from antagonistic treatments that do not cause flare-up effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pharmacology and regulatory consequences of GnRH analogues in prostate cancer. Eckstein, N., Haas, B.[2022]

GnRH and its agonists play a crucial role in regulating reproductive functions and are used to treat various conditions like prostate cancer, endometriosis, and infertility, highlighting their therapeutic efficacy.

Recent developments in small molecule GnRH antagonists present a promising alternative to peptidic forms, potentially allowing for oral administration and expanding treatment options for conditions currently managed with injections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-peptidic GnRH receptor antagonists. Armer, RE., Smelt, KH.[2019]

The GnRH analogue [(imBz1)-D-His6,Pro9-NEt]GnRH is 200 times more potent than the natural hormone in vitro, leading to significantly increased levels of LH and FSH in single-dose studies in humans.

This analogue not only shows a prolonged duration of activity but also appears to be safe, suggesting potential clinical applications for treating conditions related to hormone regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single dose responses to the gonadotropin-releasing hormone agonist analogue [(imBz 1)-D-His6,Pro9-NEt]GnRH. Doelle, GC., Evans, RM., Alexander, AN., et al.[2013]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36368706/

Oncological and reproductive outcomes for gonadotropin ... Results: Overall, 169 patients (94.4%) achieved complete remission; 58 (96.7%) had atypical endometrial hyperplasia and 111 (93.3%) had endometrial carcinoma.

2. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK279070/

Physiology of GnRH and Gonadotrophin Secretion - NCBI - NIH GnRH is the key regulator of the reproductive axis. Its pulsatile secretion determines the pattern of secretion of the gonadotropins, follicle stimulating ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1048891X24007503

Oncological and reproductive outcomes for gonadotropin ... Overall, 169 patients (94.4%) achieved complete remission; 58 (96.7%) had atypical endometrial hyperplasia and 111 (93.3%) had endometrial carcinoma. The ...

4. frontiersin.org frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1543272/full

The effectiveness of an oral gonadotropin-releasing ... This study investigated the effectiveness of an oral GnRH antagonist for retained products of conception (RPOC) carrying a risk of heavy bleeding.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2666334123000089

Clinical applications of gonadotropin-releasing hormone ... Gonadotropin-releasing hormone antagonist therapy has revolutionized endometriosis care and spares immediate surgical intervention for the greater than 30% or ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12068405/

Effects of Different Gonadotropin-Releasing Hormone ... In this study, we retrospectively collected four-year data of different GnRH-a formulations, in order to provide real-world evidence of the ...

7. frontiersin.org frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1358278/full

Effectiveness and safety of GnRH antagonist originator and ... This study aims to determine whether the live birth rates were similar between GnRH antagonist original reference product Cetrotide and generic Ferpront.

8. link.springer.com link.springer.com/article/10.1007/s00404-024-07914-3

Exposure to gonadotropin-releasing hormone agonist in ... Exposure to GnRH-a during the luteal phase of down-regulation can adversely affect pregnancy outcomes. Therefore, we recommend contraception during the IVF/ ...