Kisspeptin Administration Subcutaneously to Patients With Reproductive Disorders (KASPR)

The goal of this study is to see whether kisspeptin, a naturally occurring hormone, can stimulate the release of other reproductive hormones in women with hypothalamic amenorrhea (HA). The investigators are also examining whether kisspeptin can help women release eggs from their ovaries. Kisspeptin will be administered subcutaneously (SC) for two weeks in a pulsatile fashion. Ultrasound monitoring of ovarian follicular growth and frequent blood sampling (every 10 minutes for up to two hours) will be performed to assess the physiologic response to kisspeptin over time.

Study Overview

• Status: Recruiting
• Conditions: Hypogonadotropic Hypogonadism; Hypothalamic Amenorrhea
• Intervention / Treatment: Drug: Kisspeptin 112-121; Drug: GnRH

Detailed Description

Assignment: All study subjects will undergo the same interventions.

Delivery of Interventions:

• The subject will undergo a review of their medical history, physical exam, and screening laboratories.
• A pelvic ultrasound will be performed to assess baseline follicular size.
• A pump may be placed to administer pulsatile SC gonadotropin-releasing hormone (GnRH) for approximately six days.
• A pump will be placed to administer pulsatile SC kisspeptin for two weeks.

• During the course of kisspeptin administration, subjects will

  • Undergo q10 min blood sampling (approximately 4 sessions, 2 hours each)
  • Undergo pelvic ultrasounds (approximately 4 sessions)
• Optional q10 min sampling up to 10 hours may take place before and after the course of kisspeptin

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Study Coordinator; Phone Number: 617-724-8592; Email: MGHKisspeptinResearch@partners.org

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Study Coordinator; Phone Number: 617-724-8592; Email: MGHKisspeptinResearch@partners.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Acquired hypogonadotropic hypogonadism (hypothalamic amenorrhea, aka functional hypothalamic amenorrhea)

  • Confirmed diagnosis by medical provider supported by low sex steroids in the setting of low or inappropriately normal gonadotropins]

• Normal blood pressure (systolic BP < 140 mm Hg, diastolic < 90 mm Hg)

• Laboratory Studies:

  • Hemoglobin no less than 0.5 g/dL below the lower limit of the reference range for normal women
  • Negative serum hCG pregnancy test at screening (additional urine pregnancy test will be conducted prior to drug administration)
• Not using hormonal replacement or willing to complete an appropriate washout for that particular medication and method of administration
• No current or recent use of a medication that, in the opinion of a study investigator, can modulate the reproductive axis or willing to complete an appropriate washout for that particular medication and method of administration

Exclusion Criteria:

• Any condition (medical, mental, or behavioral) that, in the opinion of a study investigator, would likely interfere with participation in/completion of the protocol
• History of a medication reaction requiring emergency medical care

• Excessive alcohol consumption (>10 drinks/week) and/or active use of illicit drugs

  • Any active use of marijuana will be evaluated by a study medical professional to determine if it may impact study participation. Individuals who regularly use marijuana may be asked to washout as referenced in the medication washout section below

• Pregnant or trying to become pregnant
• Breast feeding
• History of bilateral oophorectomy (ovaries were removed)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• 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: Kisspeptin pump; SC administration of kisspeptin for two weeks (pulsatile, every 90 minutes)	Drug: Kisspeptin 112-121; SC administration of kisspeptin for two weeks (pulsatile, every 90 minutes); Other Names: metastin 45-54; Drug: GnRH; SC administration of GnRH for approximately six days (pulsatile, every 120 minutes); Other Names: gonadotropin-releasing hormone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of participants that achieve development of a mature follicle or show evidence of ovulation	Mature follicle achievement is defined as evidence of a follicle with maximum diameter ≥18 mm. Evidence of ovulation is defined as detection of a corpus luteum on ultrasound in combination with elevated progesterone level.	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of luteinizing hormone (LH) pulse amplitude	Difference in LH amplitude on the first day of kisspeptin administration vs the last day of kisspeptin administration	2 weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2022
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: November 21, 2022
• First Submitted That Met QC Criteria: November 21, 2022
• First Posted (Actual): December 1, 2022

Study Record Updates

• Last Update Posted (Actual): July 19, 2023
• Last Update Submitted That Met QC Criteria: July 17, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Kisspeptin; GnRH; Hypothalamic Amenorrhea; Hypogonadotropic Hypogonadism
• Additional Relevant MeSH Terms: Pathologic Processes; Endocrine System Diseases; Gonadal Disorders; Menstruation Disturbances; Hypogonadism; Amenorrhea; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones
• Other Study ID Numbers: 2022P001039

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