Kisspeptin Administration Subcutaneously to Patients With IHH

Phase 2RecruitingNCT05896293

Stephanie B. Seminara, MD36 enrolled

Overview

The goal of this study is to see whether kisspeptin, a naturally occurring hormone, can stimulate the release of other reproductive hormones in men and women with idiopathic hypogonadotropic hypogonadism (IHH). The investigators are also examining whether kisspeptin can help women release eggs from their ovaries. Kisspeptin will be administered SC for two weeks in a pulsatile fashion. Ultrasound monitoring of ovarian follicular growth (for women) and frequent blood sampling (every 10 minutes for up to 70 minutes) will be performed to assess the physiologic response to kisspeptin over time. Funding Source: FDA OOPD

Assignment: All study subjects will undergo the same interventions. Delivery of Interventions: * Each subject will undergo a review of their medical history, physical exam, and screening laboratories. * A single SC injection of leuprolide acetate may be administered approximately six days before kisspeptin administration. (Previously administration of Gonadotropin Releasing Hormone (GnRH) was used in this study.) * A pelvic ultrasound will be performed on women to assess baseline follicular size. * 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 10 sessions, 70 minutes each) * For women, undergo pelvic ultrasounds (approximately 4 sessions) * Optional q10 min sampling up to 8 hours may take place before and after the course of kisspeptin

Study Type

INTERVENTIONAL

Allocation

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Hypogonadotropic Hypogonadism

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Congenital IHH o 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) * 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 * Excessive alcohol consumption (\>10 drinks/week) and/or active use of illicit drugs o Any active use of marijuana will be evaluated by a study medical professional to determine if it may impact study participation. * Pregnant or trying to become pregnant * Breast feeding * History of: bilateral oophorectomy (both ovaries were removed), breast cancer, thromboembolic disease, coronary artery disease, stroke, thrombophilic disorders, or undiagnosed abnormal genital bleeding

Outcomes

Primary Outcomes

Average change in luteinizing hormone (LH) pulse amplitude

Average difference in LH amplitude after the first dose of kisspeptin (day 1) compared to the last dose of kisspeptin (day 15)

Time frame: 2 weeks

Secondary Outcomes

Percentage of female participants who demonstrate achievement of a mature follicle or show evidence of ovulation

Percentage of female participants that develop a mature follicle or ovulate. 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.