Kisspeptin for Delayed Puberty

Overseen By Study Coordinator

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: Massachusetts General Hospital

Disqualifiers: Chronic illness, Weight loss, others

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

Compensation: Varies

Number of Visits: 2

Duration: 1-2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine whether the hormone kisspeptin can diagnose delayed puberty in adolescents. Some children with delayed puberty begin developing independently, while others require treatment. The trial examines how kisspeptin interacts with another hormone, GnRH (Gonadotropin-releasing hormone), to identify the developmental path an adolescent might take. Boys with little to no testicular growth or girls with minimal breast development over six months may be suitable candidates for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that kisspeptin, a natural hormone in humans, helps release GnRH, which regulates the body's hormones. Studies have found that kisspeptin can safely increase hormone levels without major issues.

GnRH is a well-known hormone used in treatments for hormone-related problems. The combination of kisspeptin and GnRH has been studied in adults, and reports suggest it is generally well-tolerated.

At this early research stage, the main focus is on understanding the treatment's safety. While information about its use in teenagers with delayed puberty is limited, previous safety results in adults are encouraging. This trial is in its first phase, so safety is still being closely monitored and studied.

Overall, initial findings suggest the treatment is promising and may be a safe option, but more research is needed to confirm this. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the use of kisspeptin 112-121 in combination with GnRH for delayed puberty because it introduces a fresh approach to stimulating hormone production. Unlike traditional treatments that primarily rely on GnRH alone, kisspeptin 112-121 targets the body's natural pathways to trigger the release of reproductive hormones, potentially offering a more natural and efficient kickstart to puberty. This combination could lead to more precise control over the timing and regulation of hormone release, making it a promising alternative for those who don't respond well to existing hormone therapies.

What evidence suggests that this trial's treatments could be effective for diagnosing delayed puberty?

This trial will investigate the effects of kisspeptin and GnRH. Research has shown that kisspeptin plays a crucial role in initiating puberty by releasing key hormones necessary for sexual development. Studies have found that kisspeptin can trigger the release of luteinizing hormone (LH) and increase testosterone levels in men. This suggests that kisspeptin might help determine whether delayed puberty will resolve naturally or require medical treatment. While the findings are promising, further research is needed to confirm its usefulness in diagnosing delayed puberty. ^{1 2 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?

Inclusion Criteria

This study is not open to teenage boys.

You have not experienced any breast development changes in the past 6 months and are in the early stages of puberty.

The study does not allow participation of teenage girls.

Exclusion Criteria

history or presence of underlying condition that could cause delayed puberty (chronic illness, weight loss, abnormal cranial magnetic resonance imaging (MRI))

history of an allergic drug reaction

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous administration of kisspeptin and GnRH during two hospital admissions

1-2 weeks

2 outpatient visits, 1 overnight admission, 1 day admission

Follow-up

Participants are monitored every 6 months until they reach 18 years of age to determine if their pubertal delay was self-resolved or permanent

Variable, until age 18

What Are the Treatments Tested in This Trial?

Interventions

• GnRH
• kisspeptin 112-121

How Is the Trial Designed?

Group I: Kisspeptin, GnRH Experimental Treatment 2 Interventions

Intravenous (IV) administration of kisspeptin 112-121 0.24 nmol/kg and GnRH 75 ng/kg

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+

Published Research Related to This Trial

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]

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]

In a study of 45,059 men with prostate cancer receiving androgen deprivation therapy, the risk of major adverse cardiovascular events (MACE) was found to be significantly higher for those treated with GnRH antagonists compared to LHRH agonists, with a hazard ratio of 1.62.

Additionally, the risk of all-cause mortality was also greater for patients on GnRH antagonists versus LHRH agonists, indicating that LHRH agonists may be a safer option in terms of cardiovascular health following ADT initiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular Risk in Prostate Cancer Patients Using Luteinizing Hormone-Releasing Hormone Agonists or a Gonadotropin-Releasing Hormone Antagonist. Crawford, ED., Hafron, JM., Debruyne, F., et al.[2023]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3380939/

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. Kisspeptin ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4063702/

The kisspeptin-GnRH pathway in human reproductive health ... Kisspeptin is a recently discovered neuromodulator that controls GnRH secretion mediating endocrine and metabolic inputs to the regulation of human ...

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

NCT00914823 | Kisspeptin Administration in the Adult Kisspeptin is a naturally occurring hormone in humans that causes the release of other hormones, including gonadotropin-releasing hormone (GnRH) in the body.

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

REVIEW Kisspeptin and fertility This review examines the physiological role of kisspeptin and the kisspeptin receptor in the control of gonadotrophin and gonadal steroid hormone secretion and ...

5. academic.oup.com academic.oup.com/jcem/article/107/8/e3515/6552306

Kisspeptin Overcomes GnRH Neuronal Suppression ... Hyperprolactinemia suppresses gonadotropin-releasing hormone (GnRH)-induced luteinizing hormone (LH) pulses. The hypothalamic neuropeptide kisspeptin ...

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

Safety Evaluation of KP-10 (Metastin 45–54) Following ... Kisspeptin/metastin: a key molecule controlling two modes of gonadotrophin-releasing hormone/luteinising hormone release in female rats. J ...

7. phoenixpeptide.com phoenixpeptide.com/products/kiss-1-112-121-amide-kisspeptin-10-metastin-45-54-amide-human/

KiSS-1 (112-121) amide / Kisspeptin-10 / Metastin (45-54) ... Molecular Weight: 1302.44 ; Purity: ≥ 95% ; Validation: Exhibits correct molecular weight ; Solubility: Soluble in water ; Storage: Up to 6 months in lyophilized ...

8. 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.