Kisspeptin for Polycystic Ovary Syndrome

Overseen By Study Coordinator

Age: 18 - 65

Sex: Female

Trial Phase: Phase 1

Sponsor: Stephanie B. Seminara, MD

Must not be taking: Hormonal medications

Disqualifiers: Excessive alcohol, Illicit drugs, others

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

Compensation: Varies

Number of Visits: 3

Duration: 24 hours

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a new treatment, kisspeptin, might benefit individuals with polycystic ovary syndrome (PCOS), a condition affecting hormone levels. Researchers aim to determine how kisspeptin influences the release of specific hormones. Eligible participants must have a PCOS diagnosis and not be using hormonal medications. They should also maintain a healthy weight and normal blood pressure. 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.

Will I have to stop taking my current medications?

If you are using hormonal medications or any drugs that might affect the reproductive system, you may need to stop taking them and go through a washout period (time without taking certain medications) before joining the trial.

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

Research has shown that kisspeptin, a hormone naturally found in humans, plays a role in the reproductive system. Some studies suggest that kisspeptin can boost insulin production, potentially benefiting individuals with certain health conditions. Evidence also indicates that kisspeptin aids in egg development, which is crucial for fertility treatments.

Although kisspeptin is naturally present in the body, ongoing research aims to fully understand its safety as a treatment. This is a Phase 1 study, marking the early stages of testing its safety in humans. While detailed safety information may be limited, this phase is crucial for assessing how well people tolerate kisspeptin and identifying any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Kisspeptin 112-121 is unique because it works differently from standard treatments for Polycystic Ovary Syndrome (PCOS), which often include hormonal therapies like birth control pills or anti-androgens. Unlike these treatments, Kisspeptin directly targets the GnRH (gonadotropin-releasing hormone) pathway, which plays a crucial role in regulating reproductive hormones. Researchers are excited about Kisspeptin because it offers a more direct approach to addressing hormonal imbalances, potentially leading to more effective and faster results with fewer side effects. Plus, its administration through IV infusion allows for precise dosing and control, which could enhance its effectiveness and safety profile.

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

Research suggests that kisspeptin, which participants in this trial will receive, could be a promising treatment for polycystic ovary syndrome (PCOS). Kisspeptin, a hormone that regulates the reproductive system, has been shown in studies to increase the release of luteinizing hormone (LH), crucial for normal ovary function. In individuals with PCOS, higher kisspeptin levels suggest that the hormone might help balance hormones. Additionally, research indicates that kisspeptin could directly enhance ovarian function, including the growth of egg follicles. These findings support the potential of kisspeptin in managing PCOS symptoms. ^{1 2 3 6 7}

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 aged 18-45 with a BMI between 18.5 and 35 who have been diagnosed with PCOS. Participants should have normal blood pressure, not be pregnant or breastfeeding, avoid heavy alcohol use, and not be on hormonal medications unless they can stop them before the study.

Inclusion Criteria

Not breastfeeding

You have been diagnosed with PCOS or show similar symptoms.

Your blood pressure should be within the range of 140/90 or lower.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Review of medical history, physical exam, and screening laboratories

1 day

1 visit (in-person)

Treatment

Participants receive a 24-hour infusion of kisspeptin with up to two IV boluses

24 hours

1 visit (inpatient)

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 aims to understand how kisspeptin affects hormone patterns in those with PCOS by comparing it to GnRH (a natural hormone). It will look at the body's response to kisspeptin and its effect on luteinizing hormone levels.

How Is the Trial Designed?

Group I: kisspeptin Experimental Treatment 1 Intervention

IV administration of kisspeptin 112-121; 24-hour infusion, up to 2 boluses.

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?

Stephanie B. Seminara, MD

Lead Sponsor

Trials

10

Recruited

840+

Published Research Related to This Trial

LHRH agonists can induce a reversible state of hypogonadotrophic hypogonadism, effectively lowering plasma estrogen levels to castrate levels, which may be beneficial for treating estrogen-dependent gynecological diseases.

These agents are particularly promising for managing conditions like endometriosis, dysfunctional uterine bleeding, and uterine fibroids, offering a new treatment option that is largely free of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical aspects of LHRH analogues in gynaecology: a review. McLachlan, RI., Healy, DL., Burger, HG.[2013]

Pulsatile administration of luteinizing-hormone-releasing hormone (LHRH) effectively stimulates gonadotrophin secretion, which can be used to induce ovulation in women and promote puberty and spermatogenesis in men, highlighting its therapeutic potential in reproductive health.

In contrast, continuous infusion of LHRH leads to desensitization and inhibition of gonadotrophin secretion, but long-acting synthetic analogs of LHRH can effectively treat conditions like prostatic carcinoma and central precocious puberty, and are being explored for contraception and endometriosis treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NIH conference. Therapeutic applications of luteinizing-hormone-releasing hormone and its analogs. Cutler, GB., Hoffman, AR., Swerdloff, RS., et al.[2019]

Serum kisspeptin levels are significantly higher in women with polycystic ovary syndrome (PCOS) compared to healthy women, indicating a potential role in the hormonal imbalances associated with PCOS.

Kisspeptin levels fluctuate during the menstrual cycle in healthy women but show disrupted patterns in PCOS patients, and while age affects kisspeptin levels in healthy women, body mass index (BMI) does not significantly impact these levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Correlation between Hormonal Disturbance in PCOS Women and Serum Level of Kisspeptin. Ibrahim, RO., Omer, SH., Fattah, CN.[2022]

Kisspeptin is a crucial regulator of the reproductive system, stimulating the release of gonadotrophin releasing hormone (GnRH) and its loss can lead to fertility issues like hypogonadotrophic hypogonadism.

Recent studies indicate that administering kisspeptin can enhance gonadotrophin release in both healthy individuals and those with specific infertility conditions, suggesting its potential as a therapeutic target for fertility disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive Review on Kisspeptin and Its Role in Reproductive Disorders. Clarke, H., Dhillo, WS., Jayasena, CN.[2022]

LHRH agonists, when used in the long protocol before gonadotrophins in IVF, have been associated with higher pregnancy and live birth rates in women with PCOS, indicating their efficacy in enhancing reproductive outcomes.

The timing of LHRH agonist administration is important; starting in the early follicular phase, possibly after pre-treatment with contraceptives, can help prevent risks associated with early pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of luteinizing hormone releasing hormone agonists in polycystic ovary syndrome. Buckett, WM., Tan, SL.[2019]

In a study of 55 women with PCOS and 110 controls, serum kisspeptin levels were significantly higher in those with PCOS, suggesting a potential link between kisspeptin and the disorder.

The findings indicate that elevated kisspeptin levels could serve as a useful marker for diagnosing PCOS in young women, regardless of their body mass index.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polycystic ovary syndrome (PCOS) and kisspeptin - A Sri Lankan study. Umayal, B., Jayakody, SN., Chandrasekharan, NV., et al.[2020]

MVT-602, a KISS1R agonist, demonstrated a similar ability to induce luteinizing hormone (LH) release in healthy women compared to native kisspeptin-54, but with a delayed peak and longer duration of action, suggesting enhanced therapeutic potential.

In women with reproductive disorders like polycystic ovary syndrome (PCOS) and hypothalamic amenorrhea (HA), MVT-602 showed effective LH responses, indicating its potential utility in treating various female reproductive health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kisspeptin receptor agonist has therapeutic potential for female reproductive disorders. Abbara, A., Eng, PC., Phylactou, M., et al.[2022]

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]

Kisspeptin has shown promise in stimulating gonadotrophic-releasing hormone (GnRH) secretion, which can aid in treating reproductive disorders like hypothalamic amenorrhea and improve outcomes in in vitro fertilization (IVF) by inducing oocyte maturation with a lower risk of ovarian hyperstimulation syndrome.

Neurokinin B (NKB) and its receptor antagonists are effective in managing menopausal symptoms such as hot flushes and may also help regulate hormone levels in conditions like polycystic ovary syndrome (PCOS), highlighting their potential in treating various reproductive health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Translational Studies of Kisspeptin and Neurokinin B. Hunjan, T., Abbara, A.[2021]

Women with Polycystic Ovary Syndrome (PCOS) have higher levels of kisspeptin, suggesting that an overactive KISS1 system may disrupt the hypothalamic-pituitary-gonadal (HPG) axis, leading to symptoms like irregular menstrual cycles and increased androgen levels.

The study systematically reviewed existing literature to connect elevated kisspeptin concentrations with metabolic profiles in PCOS, indicating a potential link between kisspeptin and the hormonal imbalances characteristic of the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kisspeptin and Polycystic Ovary Syndrome. Tang, R., Ding, X., Zhu, J.[2023]

In a study of subfertile women with PCOS, higher levels of kisspeptin were significantly associated with increased luteinizing hormone (LH) and decreased follicle-stimulating hormone (FSH), indicating a potential hormonal imbalance in these patients.

The findings suggest that elevated kisspeptin levels may contribute to the hyper-stimulation of the hypothalamic-pituitary-gonadal (HPG) axis in women with PCOS, which could play a role in their subfertility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kisspeptin Variations in Patients with Polycystic Ovary Syndrome-A Prospective Case Control Study. Akad, M., Socolov, R., Furnică, C., et al.[2022]

Gonadotropin hormone analogs, like corifollitropin alfa, have been effective in fertility treatments but often require multiple injections and can vary in stability, prompting research into more efficient alternatives.

Recent developments in low-molecular-weight, orally active molecules targeting gonadotropin receptors show promise in reducing risks associated with traditional treatments and may have broader applications, including contraception and cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gonadotropins and Their Analogs: Current and Potential Clinical Applications. Anderson, RC., Newton, CL., Anderson, RA., et al.[2022]

In a study involving 28 obese and overweight women with PCOS, 28 normal weight women with PCOS, and 13 obese controls, it was found that higher levels of metastin (kisspeptin) were associated with lower insulin resistance and free androgen levels.

The research suggests that insulin resistance in PCOS may lead to increased androgen production and decreased sex hormone-binding globulin (SHBG) levels, indicating a complex relationship between metabolism and reproductive hormones in women with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma metastin levels are negatively correlated with insulin resistance and free androgens in women with polycystic ovary syndrome. Panidis, D., Rousso, D., Koliakos, G., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6530435/

Kisspeptin and Polycystic Ovary Syndrome - PMC Kisspeptin levels are higher in the PCOS population, which supports the hypothesis that an over-active KISS1 system leads to enhanced HPG-axis activity.

2. academic.oup.com academic.oup.com/jcem/article/96/8/E1228/2833644

Kisspeptin-10 Is a Potent Stimulator of LH and Increases ... Kisspeptin-10 boluses potently evoke LH secretion in men, and continuous infusion increases testosterone, LH pulse frequency, and pulse size.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00914823

NCT00914823 | Kisspeptin Administration in the Adult The goal of this study is to learn about the role of kisspeptin in the reproductive system. Kisspeptin is a naturally occurring hormone in humans that ...

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/obr.70008

Exploring the Role of Kisspeptin in Polycystic Ovary ... In this narrative review, the existing research results on the relationships among PCOS, KP, and pregnancy complications are summarized. The ...

5. frontiersin.org frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2017.00365/full

Kisspeptin/Kisspeptin Receptor System in the Ovary Experimental data gathered recently suggest a putative role of kisspeptin signaling in the direct control of ovarian function, including follicular development, ...

6. 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.

7. 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 ...