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

256 Participants Needed

Trial Summary

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).

What data supports the effectiveness of the drug Kisspeptin for Reproductive Disorders?

Research shows that gonadotropin-releasing hormone (GnRH) analogues, which are part of the treatment, are effective in restoring fertility in patients with reproductive issues and are used in treating conditions like delayed puberty. Additionally, metastin, another component, is involved in regulating reproductive functions, suggesting its potential role in treating reproductive disorders. ^{1 2 3 4 5}

Is kisspeptin safe for use in humans?

GnRH analogues, which are related to kisspeptin, have been used safely in humans for various conditions, including prostate cancer and reproductive disorders. They are generally considered safe, although some safety concerns like initial flare-ups have been noted in specific treatments. ^{1 2 6 7 8}

How is the drug kisspeptin different from other treatments for reproductive disorders?

Kisspeptin is unique because it directly stimulates the release of gonadotropin-releasing hormone (GnRH), which is crucial for regulating the reproductive system. Unlike other treatments, kisspeptin acts as a natural regulator of the hypothalamic-pituitary-gonadal axis, potentially offering a more targeted approach to managing reproductive disorders. ^{9 10 11 12 13}

What is the purpose of this trial?

This trial aims to understand how kisspeptin, a hormone that triggers the release of another hormone, affects people with certain reproductive disorders. Participants with specific reproductive health issues will receive kisspeptin to see if their bodies can respond correctly. The goal is to learn more about reproductive health and improve future diagnostics.

Research Team

Stephanie B Seminara, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Progress towards the development of non-peptide orally-active gonadotropin-releasing hormone (GnRH) antagonists: therapeutic implications. [2019]

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

Cloning, sequencing, and expression of human gonadotropin releasing hormone (GnRH) receptor. [2019]

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

Establishment and clinical application of enzyme immunoassays for determination of luteinizing hormone releasing hormone and metastin. [2011]

4. Iran pubmed.ncbi.nlm.nih.gov

Decapeptyl ameliorates cyclophosphamide-induced reproductive toxicity in male Balb/C mice: histomorphometric, stereologic and hormonal evidences. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Luteinizing hormone and follicle stimulating hormone-releasing hormone test in patients with hypothalamic-pituitary-gonadal dysfunction. [2019]

6. Germany pubmed.ncbi.nlm.nih.gov

Single dose responses to the gonadotropin-releasing hormone agonist analogue [(imBz 1)-D-His6,Pro9-NEt]GnRH. [2013]

7. Germany pubmed.ncbi.nlm.nih.gov

Clinical pharmacology and regulatory consequences of GnRH analogues in prostate cancer. [2022]

8. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Non-peptidic GnRH receptor antagonists. [2019]

9. Germany pubmed.ncbi.nlm.nih.gov

Kisspeptin expression in the brain: catalyst for the initiation of puberty. [2018]

10. England pubmed.ncbi.nlm.nih.gov

A single injection of kisspeptin-54 temporarily increases luteinizing hormone pulsatility in healthy women. [2021]

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

Kisspeptins: regulators of metastasis and the hypothalamic-pituitary-gonadal axis. [2017]

12. England pubmed.ncbi.nlm.nih.gov

Advances in clinical applications of kisspeptin-GnRH pathway in female reproduction. [2022]

13. Germany pubmed.ncbi.nlm.nih.gov

The neuroendocrine physiology of kisspeptin in the human. [2022]