Opioid Antagonism in Hypogonadotropic Hypogonadism

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

  • Hypogonadotropic Hypogonadism

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