Purpose

The goal of this study is to evaluate the effects of opioid antagonists on the hypothalamic-pituitary-gonadal axis in subjects with idiopathic hypogonadotropic hypogonadism (HH).

Condition

Eligibility

Eligible Ages
Between 18 Years and 75 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Criteria


- Confirmed diagnosis of HH with

- Low testosterone or estradiol

- Low or low-normal gonadotropin levels

- Thyroid Stimulating Hormone (TSH) and prolactin within the reference range

- Absence of abnormal pituitary or hypothalamic findings on Magnetic Resonance
Imaging (MRI)

- All other 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 opiate drug use

- No excessive alcohol consumption (<10 drinks/week)

- Not currently seeking fertility

- If applicable, able to undergo appropriate washout from hormone therapy

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

- White blood cell, platelet counts, and TSH between 90% of the lower limit and 110% of
the upper limit of the reference range

- 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

- Blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (AST), alanine
transaminase (ALT) not elevated

- Negative urine drug screening panel

- For women

- Negative serum human chorionic gonadotropin (hCG) pregnancy test at the time of
screening (additional urine pregnancy test will be conducted prior to drug
administration)

- Not breastfeeding and not pregnant

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
N/A
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
kisspeptin, GnRH, naloxone
IV administration of kisspeptin 112-121; six boluses in up to a 26-hour period. IV administration of GnRH; two boluses in up to a 26-hour period. IV administration of naloxone; one bolus and an infusion over an up to 13-hour period.
  • Drug: kisspeptin, GnRH, naloxone
    Six IV doses of kisspeptin 112-121
    Other names:
    • metastin 45-54
  • Drug: GnRH
    Two IV doses of GnRH
    Other names:
    • gonadotropin-releasing hormone
  • Drug: Naloxone
    One bolus and one infusion of naloxone

More Details

Status
Enrolling by invitation
Sponsor
Stephanie B. Seminara, MD

Study Contact

Detailed Description

Assignment: Each study subject will serve as their own control. Delivery of Interventions: - Prior to the study visit, subjects will undergo a review of their medical history and screening laboratories. - During the inpatient study, the subjects will - Period 1: Undergo q10 min blood sampling for up to 13 hours - Receive 3 kisspeptin intravenous (IV) boluses - Receive 1 gonadotropin-releasing hormone (GnRH) IV bolus - Period 2: Undergo q10 min blood sampling for up to 13 hours - Receive a naloxone bolus followed by a naloxone infusion - Receive 3 kisspeptin IV boluses - Receive 1 GnRH IV bolus

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.