Subcutaneous Kisspeptin for Fertility Issues

(KASPR Trial)

Overseen by Stephanie B. Seminara, MD

Age: 18 - 65

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Stephanie B. Seminara, MD

Must not be taking: Hormonal replacements

Disqualifiers: Pregnancy, Breastfeeding, Oophorectomy, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The goal of this study is to see whether kisspeptin, a naturally occurring hormone, can stimulate the release of other reproductive hormones in women with hypothalamic amenorrhea (HA). The investigators are also examining whether kisspeptin can help women release eggs from their ovaries. Kisspeptin will be administered subcutaneously (SC) for two weeks in a pulsatile fashion. Ultrasound monitoring of ovarian follicular growth and frequent blood sampling (every 10 minutes for up to two hours) will be performed to assess the physiologic response to kisspeptin over time.

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

You may need to stop taking certain medications before joining the trial. If you're using hormonal replacement or medications that affect reproductive hormones, you'll need to go through a 'washout period' (time without taking these medications) before participating.

What data supports the effectiveness of the drug Kisspeptin for fertility issues?

Research shows that kisspeptin plays a key role in controlling hormones related to reproduction, and studies have found that kisspeptin analogs can influence hormone levels in both animals and humans. This suggests potential for kisspeptin to help with reproductive disorders, although more research is needed to confirm its effectiveness specifically for fertility issues. ^{1 2 3 4 5}

Is subcutaneous kisspeptin safe for humans?

Research on kisspeptin, including its analogs like KP-10, has shown a favorable safety profile in animal studies, with no significant adverse effects observed in dogs at high doses. While human studies are limited, kisspeptin analogs have been evaluated in clinical settings, showing hormonal changes without reported safety concerns, suggesting it may be generally safe. ^{1 2 4 6 7}

How is the drug Kisspeptin-10 different from other fertility treatments?

Kisspeptin-10 is unique because it is a neuropeptide that stimulates the release of hormones controlling the reproductive system, and it is administered subcutaneously (under the skin), which is different from many fertility treatments that are taken orally or intravenously. It also has a specific role in regulating the hypothalamic-pituitary-gonadal axis, which is crucial for reproductive health. ^{1 2 5 8 9}

Research Team

Stephanie B. Seminara, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for women with reproductive issues like low testosterone, amenorrhea, or hypogonadotropic hypogonadism. Participants should have a confirmed diagnosis of hypothalamic amenorrhea, normal blood pressure, and hemoglobin levels within the acceptable range. They must not be pregnant, breastfeeding, using hormonal replacements without washout period or any drugs affecting the reproductive system.

Inclusion Criteria

Your blood pressure is not too high (systolic BP < 140 mm Hg, diastolic < 90 mm Hg).

I am not on, or willing to stop, any medication that affects my hormones.

Your hemoglobin levels are not too low for a woman.

Exclusion Criteria

You drink more than 10 alcoholic drinks per week or use illegal drugs.

Pregnant or trying to become pregnant

I use marijuana and understand it may affect my participation in the study.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive subcutaneous kisspeptin administration for two weeks in a pulsatile fashion

2 weeks

4 visits (in-person) for blood sampling and ultrasounds

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Kisspeptin 112-121 (Hormone Therapy)

Trial Overview The study tests if kisspeptin can trigger hormone release and egg release in ovaries of women with hypothalamic amenorrhea. Kisspeptin will be given subcutaneously in pulses over two weeks while monitoring ovarian response and hormone levels through frequent blood tests and ultrasound.

Participant Groups

Group I: Kisspeptin pump Experimental Treatment 1 Intervention

SC administration of kisspeptin for two weeks (pulsatile)

Who Is Running the Clinical Trial?

Stephanie B. Seminara, MD

Lead Sponsor

Trials

10

Recruited

840+

Findings from Research

Kisspeptin plays a crucial role in regulating reproductive functions by controlling the release of GnRH, but its therapeutic use is limited due to its susceptibility to degradation.

Investigational kisspeptin analogs have shown promise in clinical studies, causing initial increases in gonadotropin and testosterone levels, although these effects diminish over time, indicating a need for further research on their long-term efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects and therapeutic potentials of kisspeptin analogs: regulation of the hypothalamic-pituitary-gonadal axis. Matsui, H., Asami, T.[2022]

Kisspeptin-10 (KP-10) was found to have a favorable safety profile in a study involving dogs, with no signs of toxicity observed at doses up to 1,000 μg/kg administered intravenously for 14 days.

The study indicated that KP-10 effectively stimulated luteinizing hormone (LH) release, peaking at 5 minutes post-dose, suggesting its potential as a therapeutic agent for reproductive disorders without adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Evaluation of KP-10 (Metastin 45-54) Following once Daily Intravenous Administration for 14 Days in Dog. Terse, PS., Peggins, J., Seminara, SB.[2022]

In a study of 157 infertile women, those with polycystic ovary syndrome (PCOS) had significantly higher levels of kisspeptin compared to women with adequate or diminished ovarian reserves.

Kisspeptin levels were found to be negatively correlated with follicle-stimulating hormone (FSH) levels and positively correlated with total testosterone (TT) and dehydroepiandrosterone sulfate (DHEAS) levels, suggesting a complex hormonal interplay in women with different ovarian reserve patterns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there a role for kisspeptin in pathogenesis of polycystic ovary syndrome? Gorkem, U., Togrul, C., Arslan, E., et al.[2018]

In a study using immature female rats, both local and systemic administration of kisspeptin-54 significantly reduced inflammation markers in the ovaries associated with ovarian hyperstimulation syndrome (OHSS).

Kisspeptin-54 also increased the expression of Kiss1R mRNA in the ovaries and hypothalamus, suggesting a potential mechanism for its protective effects against OHSS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of intracerebroventricular and intravenous administration of Kisspeptin-54 and Gonadotropin-releasing hormone agonist in rats with ovarian hyperstimulation. Bilister Egilmez, C., Koyu, A., Azak Pazarlar, B., et al.[2022]

Kisspeptin (KP) and neurokinin B (NKB) are crucial neuropeptides that regulate reproductive health by controlling gonadotropin-releasing hormone (GnRH) activity, with disruptions in their signaling linked to conditions like congenital hypogonadotropic hypogonadism.

NKB antagonists show promise as nonsteroidal treatments for menopausal hot flashes and may also help manage reproductive disorders such as polycystic ovary syndrome and endometriosis, highlighting their potential therapeutic applications beyond reproductive health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The emerging therapeutic potential of kisspeptin and neurokinin B. Patel, B., Koysombat, K., Mills, EG., et al.[2023]

A new nonapeptide analog of metastin, named compound 26, shows improved stability in serum and retains strong binding affinity to the KISS1R receptor, which is important for regulating hormone secretion.

Compound 26 effectively reduces plasma testosterone levels in male rats and represents a promising candidate for treating hormone-dependent diseases, leading to further development of investigational analogs for clinical evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design, synthesis, and biological evaluation of novel investigational nonapeptide KISS1R agonists with testosterone-suppressive activity. Asami, T., Nishizawa, N., Matsui, H., et al.[2017]

Investigational kisspeptin analogues TAK-448 and TAK-683 effectively suppress testosterone levels in male rats, demonstrating a rapid and profound reduction to castrate levels within 3-7 days of continuous administration, which is more effective than traditional GnRH agonists like leuprolide.

Both analogues showed strong receptor-binding affinity and agonistic activity, suggesting they could be promising therapeutic options for managing reproductive functions and hormone-related diseases, such as prostate cancer, as indicated by their ability to reduce plasma prostate specific antigen (PSA) levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacologic profiles of investigational kisspeptin/metastin analogues, TAK-448 and TAK-683, in adult male rats in comparison to the GnRH analogue leuprolide. Matsui, H., Masaki, T., Akinaga, Y., et al.[2017]

Kisspeptin-10 (Kp10) injections significantly improved semen characteristics in immature Ossimi rams, increasing semen volume, sperm concentration, and the percentage of live sperm over a 6-week evaluation period.

Kp10 also enhanced testosterone production and improved sperm rheotaxis, indicating its potential as a treatment to boost reproductive health in rams.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kisspeptin injection improved the semen characteristics and sperm rheotaxis in Ossimi ram. El-Sherry, TM., Abdel-Ghani, MA., Mahmoud, GB., et al.[2020]

Females with unexplained infertility had significantly lower kisspeptin (KP) levels compared to those with male factor infertility, suggesting that KP may play a role in fertility.

A deficiency in KP was linked to reduced chances of successful implantation after intracytoplasmic sperm injection (ICSI), indicating its potential importance in reproductive health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kisspeptin: A Potential Factor for Unexplained Infertility and Impaired Embryo Implantation. Mumtaz, A., Khalid, A., Jamil, Z., et al.[2020]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Effects and therapeutic potentials of kisspeptin analogs: regulation of the hypothalamic-pituitary-gonadal axis. [2022]

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

Safety Evaluation of KP-10 (Metastin 45-54) Following once Daily Intravenous Administration for 14 Days in Dog. [2022]

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

Is there a role for kisspeptin in pathogenesis of polycystic ovary syndrome? [2018]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of intracerebroventricular and intravenous administration of Kisspeptin-54 and Gonadotropin-releasing hormone agonist in rats with ovarian hyperstimulation. [2022]

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

The emerging therapeutic potential of kisspeptin and neurokinin B. [2023]

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

Design, synthesis, and biological evaluation of novel investigational nonapeptide KISS1R agonists with testosterone-suppressive activity. [2017]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Pharmacologic profiles of investigational kisspeptin/metastin analogues, TAK-448 and TAK-683, in adult male rats in comparison to the GnRH analogue leuprolide. [2017]

8. Germany pubmed.ncbi.nlm.nih.gov

Kisspeptin injection improved the semen characteristics and sperm rheotaxis in Ossimi ram. [2020]

9. Iran pubmed.ncbi.nlm.nih.gov

Kisspeptin: A Potential Factor for Unexplained Infertility and Impaired Embryo Implantation. [2020]