Prolonged Pulsatile Kisspeptin Administration in Hypogonadotropic Hypogonadism
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
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Delivery of Interventions:
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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.
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On the day of the inpatient study, the subjects will
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Undergo q10 min blood sampling for 6 hours,
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Receive kisspeptin intravenous (IV) boluses from hour 6 to hour 44 (20 boluses total),
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Undergo q10 min blood samplings for another 6 hours,
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Receive a single GnRH IV bolus at hour 51.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Experimental: kisspeptin, GnRH • Intravenous administration of kisspeptin 112-121; 20 boluses in a 40-hour period. Intravenous administration of GnRH; one bolus. |
Drug: kisspeptin 112-121
20 intravenous doses of kisspeptin 112-121 (4 different doses of kisspeptin (randomized) in 5 sets)
Other Names:
Drug: GnRH
1 intravenous dose of GnRH
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Average change in luteinizing hormone (LH) pulse amplitude in response to kisspeptin [52 hours]
change in LH amplitude before, during and after kisspeptin administration
Secondary Outcome Measures
- Average change in LH pulse frequency in response to kisspeptin [52 hours]
change in LH frequency before and after kisspeptin administration
Eligibility Criteria
Criteria
Inclusion/exclusion criteria:
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Age 18 years and older,
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Confirmed diagnosis of HH with
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Low testosterone or estradiol,
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Low or low-normal gonadotropin levels,
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Thyroid stimulating hormone (TSH) and prolactin within the reference range,
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Absence of abnormal pituitary or hypothalamic findings on Magnetic resonance imaging (MRI),
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All other medical conditions stable and well controlled,
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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,
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No history of a medication reaction requiring emergency medical care,
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No illicit drug use,
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No excessive alcohol consumption (<10 drinks/week),
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Normal blood pressure (BP), (systolic BP < 140 mm Hg, diastolic < 90 mm Hg),
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White blood cell, platelet counts, and TSH between 90% of the lower limit and 110% of the upper limit of the reference range,
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Prolactin below 110% of the upper limit of the reference range,
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Hemoglobin
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Women: no less than 0.5 gm/dL below the lower limit of the reference range for normal women,
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Men: on adequate testosterone replacement therapy: normal male reference range,
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Blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (AST), alanine transaminase (ALT) not elevated,
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For women,
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Negative serum human chorionic gonadotropin (hCG) pregnancy test at the time of screening (additional urine pregnancy test will be conducted prior to drug administration),
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Not breastfeeding and not pregnant.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
Sponsors and Collaborators
- Stephanie B. Seminara, MD
Investigators
- Principal Investigator: Stephanie Seminara, Massachusetts General Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 313509