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Administration of Kisspeptin to Subjects With Reproductive Disorders

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ClinicalTrials.gov Identifier: NCT00914823
Recruitment Status : Recruiting
First Posted : June 5, 2009
Last Update Posted : June 19, 2018
Sponsor:
Information provided by (Responsible Party):
Stephanie B. Seminara, MD, Massachusetts General Hospital

June 4, 2009
June 5, 2009
June 19, 2018
March 2009
December 2020   (Final data collection date for primary outcome measure)
LH level [ Time Frame: 6 hours ]
Same as current
Complete list of historical versions of study NCT00914823 on ClinicalTrials.gov Archive Site
  • FSH levels [ Time Frame: 6 hours ]
  • testosterone (males) [ Time Frame: 6 hours ]
  • estradiol (females) [ Time Frame: 6 hours ]
  • CBC [ Time Frame: 1 month ]
  • BUN [ Time Frame: 1 month ]
  • creatinine [ Time Frame: 1 month ]
  • liver function studies [ Time Frame: 1 month ]
  • Prolactin levels [ Time Frame: 1 month ]
  • FSH levels [ Time Frame: 6 hours ]
  • testosterone (males) [ Time Frame: 6 hours ]
  • estradiol (females) [ Time Frame: 6 hours ]
  • CBC [ Time Frame: 1 month ]
  • BUN [ Time Frame: 1 month ]
  • creatinine [ Time Frame: 1 month ]
  • liver function studies [ Time Frame: 1 month ]
Not Provided
Not Provided
 
Administration of Kisspeptin to Subjects With Reproductive Disorders
Kisspeptin Administration in the Adult
The investigators are seeking participants for a study of the role of kisspeptin in the reproductive system. Kisspeptin is a naturally occuring hormone in humans that stimulates the production of reproductive hormones. The investigators hypothesize that kisspeptin administration will be a useful tool for characterizing certain reproductive disorders.

The master reproductive hormone GnRH (gonadotropin-releasing hormone) is essential for normal reproductive function. People with hypogonadotropic hypogonadism (IHH), hyperprolactinemia, and polycystic ovarian syndrome (PCOS) do not secrete or respond to GnRH in a normal way. In this study, investigators will give participants, kisspeptin— a hormone that is naturally found in the human body and is known to be a powerful stimulus of GnRH secretion. They may also give participants GnRH to determine if participants will be able to fully respond to kisspeptin.

The goal of this study is to use kisspeptin administration to probe the condition of GnRH neurons in people with various reproductive disorders to better understand the underlying reasons for the disorders. Investigators hope to gain new insights into GnRH neuronal function (or dysfunction) that will lead to better diagnostics in the future.

The investigators are seeking men and women with hypogonadotropic hypogonadism (HH) and hyperprolactinemia, as well as women with PCOS. Study participation involves 1 to 2 outpatient visits and 1 to 2, 3-15-hour hospital admission(s) where participants will receive kisspeptin and/or gonadotropin-releasing hormone (GnRH) through an intravenous line (IV). Remuneration is up to $800 for study completion. Individuals interested in learning more may email MGHKisspeptinResearch@partners.org or call 617-726-5383.

Interventional
Phase 1
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
  • Hypogonadotropic Hypogonadism
  • Kallmann Syndrome
  • GnRH Deficiency
  • PCOS
  • Polycystic Ovarian Syndrome
  • Hyperprolactinemia
  • Drug: kisspeptin 112-121
    one or more intravenous doses of kisspeptin 112-121, and/or short infusion (up to 12 hours) of kisspeptin 112-121
    Other Name: metastin 45-54
  • Drug: GnRH
    One or more intravenous doses of GnRH
    Other Name: gonadotropin-releasing hormone
Experimental: kisspeptin, GnRH
intravenous administration of kisspeptin 112-121 and/or GnRH
Interventions:
  • Drug: kisspeptin 112-121
  • Drug: GnRH
Chan YM, Lippincott MF, Butler JP, Sidhoum VF, Li CX, Plummer L, Seminara SB. Exogenous kisspeptin administration as a probe of GnRH neuronal function in patients with idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2014 Dec;99(12):E2762-71. doi: 10.1210/jc.2014-2233.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
496
100
December 2020
December 2020   (Final data collection date for primary outcome measure)

A. Healthy Volunteers

All healthy volunteers will meet the following criteria:

History:

  • history of normal puberty with respect to onset and pace,
  • no history of chronic disease,
  • no prescription medications for at least 2 months with the exception of seasonal allergy medications and hormone replacement therapy,
  • no illicit drug use,
  • no excessive alcohol consumption (< 10 drinks/week),
  • no history of a medication reaction requiring emergency medical care,
  • no difficulty with blood draws,
  • for women, not breastfeeding and not pregnant.

Physical examination:

  • BMI > 18.5 and < 30 kg/m2,
  • normal blood pressure, (systolic BP < 140 mm Hg, diastolic < 90 mm Hg). Laboratory studies: (per MGH reference ranges unless noted otherwise)
  • white blood cell, platelet counts, prolactin, and TSH between 90% of the lower limit and 110% of the upper limit of the reference range,
  • normal hemoglobin,
  • BUN, creatinine, AST, ALT not elevated,
  • normal levels of LH, FSH, and sex steroids (estradiol or testosterone).

Additional criteria based on subject population:

  1. Healthy Men (n=80, for 40 finishing the study) will be recruited who meet the above criteria and:

    History:

    • age between 21 and 40 years,
    • normal erectile and ejaculatory function by report, no history of reproductive disorders (i.e. no history of cryptorchidism).

    Physical examination:

    • testicular volume >15 ml by Prader orchidometer.

  2. Healthy women (n=240, for 120 finishing the study, 40 each to be studied in the follicular, pre-ovulatory, and luteal phases of the menstrual cycle) will be recruited who meet the above criteria and:

    History:

    • age between 21 and 40 years,

    • menstrual cycles between 25 and 35 days in duration, at least 11 periods/year, with no more than 5 days variability in cycle duration,
    • no oral contraceptives for at least 2 months.

    Physical examination:

    • no evidence for androgen excess (hirsutism or acne).

    Laboratory studies:

    • negative serum hCG pregnancy test at the time of screening, (additional urine pregnancy test will be conducted prior to drug administration),

    • if to receive estradiol treatment as a part of this study, negative screening for Factor V Leiden.

  3. Healthy postmenopausal women (n=20, for 10 finishing the study) will be recruited who meet the above criteria and:

    History:

    • age between 50 and 60 years,

    • 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.

    Physical examination:

    • no evidence for androgen excess (hirsutism or acne).

    Laboratory studies:

    • if to receive estradiol treatment as a part of this study, negative screening for Factor V Leiden.

    B. Subjects with Reproductive Disorders

    All subjects with reproductive disorders will meet the following criteria:

    History:

    • 18 years or older,

    • all 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),

    • for women, not breastfeeding and not pregnant,

    • if applicable, able to undergo appropriate washout from hormone therapy.

    Physical Examination:

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

    Laboratory Studies:

    • 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 with the exception of participants with hyperprolactinemia who by definition will have elevated levels of prolactin.
    • 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; off testosterone replacement therapy: no lower than 0.5 gm/dL below the lower limit of the reference range for normal women (> 11.5 gm/dL in our laboratory), as men with hypogonadism off treatment have low serum testosterone levels which causes hemoglobin concentrations to fall to the female range,
    • BUN, creatinine, AST, ALT not elevated,
    • for women, negative serum hCG pregnancy test at the time of screening (additional urine pregnancy test will be conducted prior to drug administration).

    Additional criteria based on subject population:

1. Men and women with hypogonadotropic hypogonadism (n= 120: 80 males, 40 females to have 40 males and 20 females complete the study). All subjects will have confirmed diagnosis by low sex steroids in the setting of low or inappropriately normal gonadotropins. If needed to verify clinical criteria, additional diagnostic labs and imaging tests may be performed including but not limited to: ferritin, prolactin, sex steroids, FSH, LH and brain MRI.

2. Women with Polycystic Ovarian Syndrome (PCOS) (n=20, for 10 finishing the study) All subjects will have a confirmed diagnosis of PCOS as evidenced by 2 or more of the following: oligoamenorrhea, clinical or biochemical hyperandrogenism, and polycystic ovarian morphology, and exclusion of identifiable conditions that would result in this pattern. If needed to verify clinical criteria, additional diagnostic labs may be drawn including but not limited to: 17-OHP, sex steroids, FSH, LH.

3. Men and women with hyperprolactinemia (n=16: 8 males, 8 females to have 4 males and 4 females complete the study). All subjects will have confirmed diagnosis by elevated levels of prolactin measured via blood test and MRI imaging confirming no pituitary abnormality or a microprolactinoma (<10 mm). Patients with a macroprolactinoma will be excluded. We will enroll subjects when they first present with hyperprolactinemia prior to receiving medication or subjects being treated with the dopamine agonist bromocriptine only. We will ask subjects being treated with bromocriptine to complete a washout period prior to the kisspeptin administration visit(s). The washout period will last at least 2 weeks. We will perform a blood test prior to the kisspeptin administration visit(s) to confirm elevated levels of prolactin.

Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
Yes
Contact: Isabella McDonald 617-726-8484 MGHKisspeptinResearch@partners.org
United States
 
 
NCT00914823
2008-P-002486
Yes
Not Provided
Not Provided
Stephanie B. Seminara, MD, Massachusetts General Hospital
Massachusetts General Hospital
Not Provided
Principal Investigator: Stephanie B. Seminara, MD Massachusetts General Hospital
Massachusetts General Hospital
June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP