Prolonged Pulsatile Kisspeptin Administration in Hypogonadotropic Hypogonadism

Study Overview
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Brief Summary
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The goal of this study is to develop novel treatments for patients with a condition called hypogonadotropic hypogonadism (HH) through the use of exogenous kisspeptin.

Detailed Description
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Assignment: Each study subject will serve as their own control. The order of kisspeptin doses will be randomized within each set/exposure. Delivery of Interventions: Prior to the study visit, subjects will undergo a review of their medical history and screening laboratories. Subjects will also wear a gonadotropin releasing hormone (GnRH) pump prior to the inpatient study visit. On the day of the inpatient study, the subjects will Undergo q10 min blood sampling for 6 hours, Receive kisspeptin intravenous (IV) boluses from hour 6 to hour 44 (20 boluses total), Undergo q10 min blood samplings for another 6 hours, Receive a single GnRH IV bolus at hour 51.

Official Title
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Prolonged Pulsatile Kisspeptin Administration in Hypogonadotropic Hypogonadism

Conditions
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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/exclusion criteria: Age 18 years and older, Confirmed diagnosis of HH with Low testosterone or estradiol, Low or low-normal gonadotropin levels, Thyroid stimulating hormone (TSH) and prolactin within the reference range, Absence of abnormal pituitary or hypothalamic findings on Magnetic resonance imaging (MRI), All other medical conditions stable and well controlled, No prescription medications known to affect reproductive endocrine function for at least 2 months or for 5 half-lives of the drug (whichever is shorter) except for medications used to treat the subject's reproductive condition, No history of a medication reaction requiring emergency medical care, No illicit drug use, No excessive alcohol consumption (<10 drinks/week), Normal blood pressure (BP), (systolic BP < 140 mm Hg, diastolic < 90 mm Hg), White blood cell, platelet counts, and TSH between 90% of the lower limit and 110% of the upper limit of the reference range, Prolactin below 110% of the upper limit of the reference range, Hemoglobin Women: no less than 0.5 gm/dL below the lower limit of the reference range for normal women, Men: on adequate testosterone replacement therapy: normal male reference range, Blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (AST), alanine transaminase (ALT) not elevated, For women, Negative serum human chorionic gonadotropin (hCG) pregnancy test at the time of screening (additional urine pregnancy test will be conducted prior to drug administration), Not breastfeeding and not pregnant.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: kisspeptin, GnRH<br>• Intravenous administration of kisspeptin 112-121; 20 boluses in a 40-hour period. Intravenous administration of GnRH; one bolus. | Drug: kisspeptin 112-121<br>* 20 intravenous doses of kisspeptin 112-121 (4 different doses of kisspeptin (randomized) in 5 sets)<br>* Other names: metastin 45-54;Drug: GnRH<br>* 1 intravenous dose of GnRH<br>* Other names: gonadotropin-releasing hormone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average change in luteinizing hormone (LH) pulse amplitude in response to kisspeptin | Change in LH amplitude before, during and after kisspeptin administration | 52 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average change in LH pulse frequency in response to kisspeptin | Change in LH frequency before and after kisspeptin administration | 52 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypogonadotropic hypogonadism, kisspeptin