Prolonged Pulsatile Kisspeptin Administration in Hypogonadotropic Hypogonadism

Stephanie B. Seminara, MD

Status and phase: Completed; Phase 2

Conditions: Hypogonadotropic Hypogonadism

Treatments: Drug: GnRH; Drug: kisspeptin 112-121

Study type: Interventional

Funder types: Other

Identifiers

NCT04648969

313509

Details and patient eligibility

About

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.

Full 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.

Enrollment: 18 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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18 participants in 1 patient group

Experimental: kisspeptin, GnRH

Experimental group

Description:

• Intravenous administration of kisspeptin 112-121; 20 boluses in a 40-hour period. Intravenous administration of GnRH; one bolus.

Treatment:

Drug: kisspeptin 112-121

Drug: GnRH