Kisspeptin for Polycystic Ovary Syndrome

Recruiting in Palo Alto (17 mi)

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 medications

Disqualifiers: Excessive alcohol, Illicit drugs, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial involves giving kisspeptin and another hormone to people with PCOS to see how it affects their hormone levels. The goal is to understand if kisspeptin can help regulate their reproductive hormones. Kisspeptin has recently emerged as a key regulator of the reproductive system in women and has been shown to stimulate the secretion of another important hormone.

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.

What evidence supports the effectiveness of the drug Kisspeptin for treating Polycystic Ovary Syndrome?

Research shows that a kisspeptin receptor agonist, MVT-602, can increase luteinizing hormone (LH) levels in women with PCOS, similar to its effects in healthy women, suggesting it may help regulate reproductive hormones. Additionally, kisspeptin levels are higher in women with PCOS, indicating its role in the condition and potential as a treatment target. ^{1 2 3 4 5}

Is Kisspeptin safe for use in humans?

Kisspeptin has been studied for its role in reproductive health and has shown promise in treatments like in vitro fertilization (IVF) with reduced risk of complications. It has been used to stimulate hormone secretion in both healthy individuals and those with reproductive disorders, suggesting it is generally safe for human use. ^{4 6 7 8 9}

How is the drug Kisspeptin different from other treatments for PCOS?

Kisspeptin is unique because it directly influences the release of gonadotropin-releasing hormone (GnRH), which is crucial for regulating hormones involved in ovulation. This makes it different from other treatments that may not target the hormonal imbalance at this specific level, potentially offering a novel approach for managing PCOS symptoms. ^{3 10 11 12 13}

Research Team

Stephanie B. Seminara, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

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 are between 18 and 45 years old.

You have been diagnosed with PCOS or show similar symptoms.

Trial Timeline

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

Treatment Details

Interventions

• GnRH (Hormone Therapy)
• Kisspeptin 112-121 (Hormone Therapy)

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.

Participant Groups

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 Canada for the following indications:

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

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

Kisspeptin receptor agonist has therapeutic potential for female reproductive disorders. [2022]

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

Plasma metastin levels are negatively correlated with insulin resistance and free androgens in women with polycystic ovary syndrome. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Kisspeptin Variations in Patients with Polycystic Ovary Syndrome-A Prospective Case Control Study. [2022]

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

NIH conference. Therapeutic applications of luteinizing-hormone-releasing hormone and its analogs. [2019]

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

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

6. England pubmed.ncbi.nlm.nih.gov

Clinical aspects of LHRH analogues in gynaecology: a review. [2013]

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

Clinical Translational Studies of Kisspeptin and Neurokinin B. [2021]

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

Gonadotropins and Their Analogs: Current and Potential Clinical Applications. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Use of luteinizing hormone releasing hormone agonists in polycystic ovary syndrome. [2019]

10. Egypt pubmed.ncbi.nlm.nih.gov

The Correlation between Hormonal Disturbance in PCOS Women and Serum Level of Kisspeptin. [2022]

11. India pubmed.ncbi.nlm.nih.gov

Polycystic ovary syndrome (PCOS) and kisspeptin - A Sri Lankan study. [2020]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Kisspeptin and Polycystic Ovary Syndrome. [2023]

13. Korea (South) pubmed.ncbi.nlm.nih.gov

Comprehensive Review on Kisspeptin and Its Role in Reproductive Disorders. [2022]