Elucidating Kisspeptin Physiology by Blocking Kisspeptin Signaling

NCT01438073 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 2011-P-001564
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hypogonadotropic Hypogonadism; Healthy Postmenopausal Women; Agonadism

Outcome Measures

Primary Outcomes (1)

• Average difference in Luteinizing Hormone (LH) concentration at the beginning and end of kisspeptin infusion

  24 hours

Secondary Outcomes (2)

• 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

Study Arms (1)

kisspeptin, GnRH

EXPERIMENTAL

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; Drug: GnRH

Interventions

kisspeptin 112-121 DRUG

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)

Also known as: metastin 45-54

kisspeptin, GnRH

GnRH DRUG

Single intravenous dose of GnRH (2.5-250 ng/kg)

Also known as: gonadotropin-releasing hormone

kisspeptin, GnRH

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• 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.

  PMID: 28368443 DERIVED

MeSH Terms

Conditions

Hypogonadism; Gonadal Dysgenesis

Interventions

Gonadotropin-Releasing Hormone

Condition Hierarchy (Ancestors)

Gonadal Disorders; Endocrine System Diseases; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Stephanie B Seminara, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Reproductive Endocrine Unit; Professor of Medicine, Harvard Medical School; Director, MGH Harvard Center for Reproductive Medicine

Study Record Dates

• First Submitted: August 24, 2011
• First Posted: September 21, 2011
• Study Start: September 1, 2011
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: July 11, 2022

Record last verified: 2022-07

Locations

US (1)