Clinical trial NCT01438073: Elucidating Kisspeptin Physiology by Blocking Kisspeptin Signaling
Official title: Elucidating Kisspeptin Physiology by Blocking Kisspeptin Signaling
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypogonadotropic Hypogonadism
Healthy Postmenopausal Women
Agonadism
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2011-09-21
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

Detailed description: Please contact study staff for a detailed description.

Eligibility criteria: 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.

Primary outcomes:
measure: Average difference in Luteinizing Hormone (LH) concentration at the beginning and end of kisspeptin infusion
timeFrame: 24 hours
Secondary outcomes:
measure: Average difference in testosterone concentration at the beginning and end of kisspeptin infusion (males)
timeFrame: 24 hours
measure: Average difference in estradiol concentration at the beginning and end of kisspeptin infusion (females)
timeFrame: 24 hours
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Stephanie B Seminara, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.