Prolonged Pulsatile Kisspeptin Administration in Hypogonadotropic Hypogonadism

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.

Study Overview

• Status: Completed
• Conditions: Hypogonadotropic Hypogonadism
• Intervention / Treatment: Drug: kisspeptin 112-121; Drug: GnRH

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: metastin 45-54; Drug: GnRH; 1 intravenous dose of GnRH; Other Names: gonadotropin-releasing hormone

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Stephanie B. Seminara, MD
• Investigators: Principal Investigator: Stephanie Seminara, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2019
• Primary Completion (Actual): August 31, 2025
• Study Completion (Actual): August 31, 2025

Study Registration Dates

• First Submitted: November 11, 2020
• First Submitted That Met QC Criteria: November 24, 2020
• First Posted (Actual): December 2, 2020

Study Record Updates

• Last Update Posted (Actual): February 18, 2026
• Last Update Submitted That Met QC Criteria: February 13, 2026
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: hypogonadotropic hypogonadism, kisspeptin
• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Hypogonadism; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Gonadotropin-Releasing Hormone
• Other Study ID Numbers: 313509

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No