Elucidating Kisspeptin Physiology by Blocking Kisspeptin Signaling

The investigators are looking for subjects to complete a study on the role of kisspeptin in the reproductive system. Kisspeptin is a naturally occurring hormone in humans that tells the body to produce other reproductive hormones. However, giving someone a continued amount of kisspeptin over a period of time can have the opposite effect and tell the body to, for a short time, stop making hormones needed for reproduction. By giving 24-hour infusions of kisspeptin, the investigators hope to learn more about the role kisspeptin has in the way bodies function normally and the role it has in conditions that affect the reproductive system.

Study Overview

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

Detailed Description

Please contact study staff for a detailed description.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

A. Healthy Subjects

All healthy subjects will meet the following criteria:

• normal puberty with respect to onset and pace,
• no difficulty with blood draws,
• no prescription medications for at least 2 months with the exception of asthma medication (albuterol only), hypercholesterolemia medication and psychiatric medication,
• no illicit drug use or excessive alcohol consumption (>10 drinks/week),
• no history of a medication reaction requiring emergency medical care,
• normal physical exam and laboratory studies within protocol reference ranges.

Additional criteria based on subject population:

1. Healthy Men:

   • between 21 and 40 years old,
   • normal erectile and ejaculatory function, no history of reproductive disorders,
   • testicular volume >15 ml.

2. Healthy women:

   • between 21 and 40 years old,
   • not breastfeeding or pregnant,
   • menstrual cycles between 25 and 35 days in duration with no more than 5 days variability in cycle duration,
   • no evidence for androgen excess (hirsutism or acne),

3. Healthy postmenopausal women:

   • between 48 and 60 years old,
   • no menstrual periods within the last year,
   • previous history of menstrual cycles between 25 and 35 days in duration, with no more than 5 days variability in cycle duration,
   • if applicable, able to undergo washout from hormone therapy,
   • no evidence for androgen excess (hirsutism or acne),
   • negative screening for Factor V Leiden for those who might receive estradiol treatment as a part of this study.

B. Subjects with Reproductive Disorders

All subjects with reproductive disorders will meet the following criteria:

• all medical conditions stable and well controlled, medications allowed include asthma medication (albuterol only), hypercholesterolemia medication and psychiatric medication,
• no medications known to affect reproductive endocrine function for at least 2 months 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 or excessive alcohol consumption (>10 drinks/week),
• for women, not breastfeeding or pregnant,
• if applicable, able to undergo appropriate washout from hormone therapy,
• normal physical exam and laboratory studies within protocol reference ranges,

Additional criteria based on subject population:

1. Men and women with hypogonadotropic hypogonadism,

   • 18 years or older,
   • Confirmed diagnosis by low sex steroids in the setting of low or inappropriately normal gonadotropins,
   • If needed, additional labs and imaging tests may be performed.

2. Agonadal men,

   • Between 18 and 60 years old.

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, GnRH; 24-hour continuous intravenous infusion of kisspeptin 112-121 (12.5-40 mcg/kg/h), single intravenous dose of kisspeptin 112-121 (0.313-13.19 mcg/kg), and single bolus of GnRH (gonadotropin-releasing hormone) (2.5-250 ng/kg)	Drug: kisspeptin 112-121; 24-h continuous intravenous infusion of kisspeptin 112-121 (12.5-40 mcg/kg/h), single intravenous dose of kisspeptin 112-121 (0.313-13.19 mcg/kg); Other Names: metastin 45-54; Drug: GnRH; Single intravenous dose of GnRH (2.5-250 ng/kg); Other Names: gonadotropin-releasing hormone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Average difference in Luteinizing Hormone (LH) concentration at the beginning and end of kisspeptin infusion	24 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Average difference in testosterone concentration at the beginning and end of kisspeptin infusion (males)	24 hours
Average difference in estradiol concentration at the beginning and end of kisspeptin infusion (females)	24 hours

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital

Publications and helpful links

General Publications

• Lippincott MF, Chan YM, Rivera Morales D, Seminara SB. Continuous Kisspeptin Administration in Postmenopausal Women: Impact of Estradiol on Luteinizing Hormone Secretion. J Clin Endocrinol Metab. 2017 Jun 1;102(6):2091-2099. doi: 10.1210/jc.2016-3952.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2011
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: August 24, 2011
• First Submitted That Met QC Criteria: September 20, 2011
• First Posted (Estimate): September 21, 2011

Study Record Updates

• Last Update Posted (Actual): July 11, 2022
• Last Update Submitted That Met QC Criteria: July 7, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Hypogonadism; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones
• Other Study ID Numbers: 2011-P-001564

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No