Opioid Antagonism in Hypogonadotropic Hypogonadism

Hypogonadotropic Hypogonadism Clinical Trial

Official title:

Opioid Antagonism in Hypogonadotropic Hypogonadism

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04975334
• Other study ID #: 313510
• Status: Enrolling by invitation
• Phase: Phase 2
• Start date: August 31, 2024
• Est. completion date: May 31, 2025

Study information

• Verified date: March 2024
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 23
• Est. completion date: May 31, 2025
• Est. primary completion date: May 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

• 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

Related Conditions & MeSH terms

• Hypogonadism
• Hypogonadotropic Hypogonadism

Intervention

Drug:
• kisspeptin, GnRH, naloxone
Six IV doses of kisspeptin 112-121
• GnRH
Two IV doses of GnRH
• Naloxone
One bolus and one infusion of naloxone

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Stephanie B. Seminara, MD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Average change in Luteinizing Hormone (LH) pulse frequency	Change in LH pulse frequency before and during naloxone infusion	Before and during treatment
Secondary	Average change in LH pulse amplitude	change in LH pulse amplitude before and during naloxone infusion	Before and during treatment