Subcutaneous Kisspeptin for Fertility Issues

(KASPR Trial)

Overseen By Study Coordinator

Age: 18 - 65

Sex: Female

Trial Phase: Phase 1

Sponsor: Stephanie B. Seminara, MD

Must not be taking: Hormonal replacements

Disqualifiers: Pregnancy, Breastfeeding, Oophorectomy, others

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

Compensation: Varies

Number of Visits: 5

Duration: 2 weeks

13 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the hormone kisspeptin (administered as Kisspeptin 112-121) can aid women with hypothalamic amenorrhea, a condition where menstruation stops due to low hormone levels, by enhancing reproductive hormone release and egg production. Participants will receive kisspeptin through a small pump under the skin for two weeks, with regular monitoring to assess their body's response. Women diagnosed with hypothalamic amenorrhea and stable blood pressure may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that kisspeptin, a hormone naturally found in the body, is under study for its potential to address fertility issues, such as amenorrhea and infertility. Studies suggest that kisspeptin may safely support reproductive health.

Kisspeptin is generally well-tolerated, with no major side effects reported in studies so far. This suggests the treatment does not cause serious harm. Additionally, research indicates that kisspeptin can aid in egg development, which is promising for those seeking to improve fertility.

Although this trial is in its early stages, safety data from previous research is encouraging. Prospective participants should know that kisspeptin has been used safely in other studies to support reproductive health. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard fertility treatments, which often involve hormone injections like FSH or LH to stimulate ovulation, kisspeptin is a naturally occurring peptide that plays a crucial role in activating the reproductive hormone cascade. Researchers are excited about Kisspeptin 112-121 because it could offer a more natural and potentially safer alternative by directly stimulating the body's own reproductive hormones without the risk of ovarian hyperstimulation syndrome, a common side effect of traditional treatments. Additionally, this treatment is administered subcutaneously through a pump, which allows for precise, pulsatile delivery, mimicking the body's natural hormone release patterns and potentially improving treatment outcomes.

What evidence suggests that kisspeptin might be an effective treatment for fertility issues?

Research shows that kisspeptin, a natural hormone, plays a crucial role in triggering reproductive hormones. In earlier studies, kisspeptin showed promise in restoring fertility by promoting the release of these hormones. People lacking kisspeptin receptors often face fertility problems, highlighting its importance. Studies have found that different types of kisspeptin, such as KP-54 and KP-10, affect hormone release in various ways. This trial will investigate the effects of subcutaneous kisspeptin administration over two weeks. While some research in healthy women has shown encouraging results, more studies are needed to fully understand its effectiveness in treating conditions like hypothalamic amenorrhea. ^{2 3 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 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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Kisspeptin 112-121

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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-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]

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]

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 (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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12112093/

Kisspeptins Regulating Fertility: Potential Future Therapeutic ... Exogenous administration of kisspeptins appears to hold significant promise in restoring fertility, with ongoing studies in their application in ovarian ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5413024/

Mechanistic insights into the more potent effect of KP-54 ... Data suggest that KP-54 and KP-10 are not equally effective at eliciting reproductive hormone secretion after peripheral delivery.

3. joe.bioscientifica.com joe.bioscientifica.com/view/journals/joe/208/2/97.pdf

REVIEW Kisspeptin and fertility Mice and humans lacking kisspeptin receptor expression show a phenotype of hypogonadotrophic hypogonadism and conse- quent infertility (de Roux et al. 2003, ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT00914823

NCT00914823 | Kisspeptin Administration in the Adult The goal of this study is to use kisspeptin administration to probe the condition of GnRH neurons in people with various reproductive disorders to better ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1155/2014/512650

Effects of the Hormone Kisspeptin on Reproductive ... There have been some differences in the data collected from the small number of studies of kisspeptin administration to healthy women so far, with some evidence ...

6. journals.sagepub.com journals.sagepub.com/doi/abs/10.1177/10915818211023459

Safety Evaluation of KP-10 (Metastin 45–54) Following ... ... kisspeptin-145, is a potential therapeutic agent for reproductive disorders such as infertility, amenorrhea, and pubertal delay. A safety ...

7. e-enm.org e-enm.org/journal/view.php?doi=10.3803/enm.2015.30.2.124

Comprehensive Review on Kisspeptin and Its Role in ... This review aims to concisely summarize what is known about kisspeptin as a regulator of reproductive function, and provide an update on recent ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1471489222001461

Novel therapeutic avenues for kisspeptin Recent studies have demonstrated that kisspeptin can induce a more physiological degree of oocyte maturation during in vitro fertilisation treatment.