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
Arm | Description | Assigned 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. |
|
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