Clinical trial NCT04648969: Prolonged Pulsatile Kisspeptin Administration in Hypogonadotropic Hypogonadism
Official title: Prolonged Pulsatile Kisspeptin Administration in Hypogonadotropic Hypogonadism
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hypogonadotropic Hypogonadism
Keywords: hypogonadotropic hypogonadism, kisspeptin
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2020-12-02
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: * 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Average change in luteinizing hormone (LH) pulse amplitude in response to kisspeptin
timeFrame: 52 hours
Secondary outcomes:
measure: Average change in LH pulse frequency in response to kisspeptin
timeFrame: 52 hours
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Stephanie Seminara
role: PRINCIPAL_INVESTIGATOR
References: