Kisspeptin Administration Subcutaneously to Patients With Reproductive Disorders

Study Overview
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Brief Summary
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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.

Detailed Description
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Assignment: All study subjects will undergo the same interventions. Delivery of Interventions: The subject will undergo a review of their medical history, physical exam, and screening laboratories. A pelvic ultrasound will be performed to assess baseline follicular size. A pump may be placed to administer pulsatile SC gonadotropin-releasing hormone (GnRH) for approximately six days. A pump will be placed to administer pulsatile SC kisspeptin for two weeks. During the course of kisspeptin administration, subjects will Undergo q10 min blood sampling (approximately 4 sessions, 2 hours each) Undergo pelvic ultrasounds (approximately 4 sessions) Optional q10 min sampling up to 10 hours may take place before and after the course of kisspeptin

Official Title
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Kisspeptin Administration Subcutaneously to Patients With Reproductive Disorders

Conditions
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Hypothalamic Amenorrhea, Hypogonadotropic Hypogonadism

Intervention / Treatment
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* Drug: Kisspeptin 112-121
* Drug: GnRH


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acquired hypogonadotropic hypogonadism (hypothalamic amenorrhea, aka functional hypothalamic amenorrhea) • Confirmed diagnosis by medical provider supported by low sex steroids in the setting of low or inappropriately normal gonadotropins] Normal blood pressure (systolic BP < 140 mm Hg, diastolic < 90 mm Hg) Laboratory Studies: Hemoglobin no less than 0.5 g/dL below the lower limit of the reference range for normal women Negative serum hCG pregnancy test at screening (additional urine pregnancy test will be conducted prior to drug administration) Not using hormonal replacement or willing to complete an appropriate washout for that particular medication and method of administration No current or recent use of a medication that, in the opinion of a study investigator, can modulate the reproductive axis or willing to complete an appropriate washout for that particular medication and method of administration Exclusion Criteria: Any condition (medical, mental, or behavioral) that, in the opinion of a study investigator, would likely interfere with participation in/completion of the protocol History of a medication reaction requiring emergency medical care Excessive alcohol consumption (>10 drinks/week) and/or active use of illicit drugs • Any active use of marijuana will be evaluated by a study medical professional to determine if it may impact study participation. Individuals who regularly use marijuana may be asked to washout as referenced in the medication washout section below Pregnant or trying to become pregnant Breast feeding History of bilateral oophorectomy (ovaries were removed)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Kisspeptin pump<br>SC administration of kisspeptin for two weeks (pulsatile, every 90 minutes) | Drug: Kisspeptin 112-121<br>* SC administration of kisspeptin for two weeks (pulsatile, every 90 minutes)<br>* Other names: metastin 45-54;Drug: GnRH<br>* SC administration of GnRH for approximately six days (pulsatile, every 120 minutes)<br>* Other names: gonadotropin-releasing hormone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of participants that achieve development of a mature follicle or show evidence of ovulation | Mature follicle achievement is defined as evidence of a follicle with maximum diameter ≥18 mm. Evidence of ovulation is defined as detection of a corpus luteum on ultrasound in combination with elevated progesterone level. | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of luteinizing hormone (LH) pulse amplitude | Difference in LH amplitude on the first day of kisspeptin administration vs the last day of kisspeptin administration | 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypothalamic Amenorrhea, Hypogonadotropic Hypogonadism, Kisspeptin, GnRH