Opioid Antagonism in Hypogonadotropic Hypogonadism

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).

Study Overview

• Status: Enrolling by invitation
• Conditions: Hypogonadotropic Hypogonadism
• Intervention / Treatment: Drug: GnRH; Drug: Naloxone; Drug: kisspeptin, GnRH, naloxone

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

• Study Type: Interventional
• Enrollment (Estimated): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: GnRH; Two IV doses of GnRH; Other Names: gonadotropin-releasing hormone; Drug: Naloxone; One bolus and one infusion of naloxone; Drug: kisspeptin, GnRH, naloxone; Six IV doses of kisspeptin 112-121; Other Names: metastin 45-54

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average change in Luteinizing Hormone (LH) pulse frequency	Change in LH pulse frequency before and during naloxone infusion	Before and during treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average change in LH pulse amplitude	change in LH pulse amplitude before and during naloxone infusion	Before and during treatment

Collaborators and Investigators

• Sponsor: Stephanie B. Seminara, MD
• Investigators: Principal Investigator: Stephanie Seminara, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 31, 2024
• Primary Completion (Estimated): May 31, 2025
• Study Completion (Estimated): May 31, 2025

Study Registration Dates

• First Submitted: July 15, 2021
• First Submitted That Met QC Criteria: July 15, 2021
• First Posted (Actual): July 23, 2021

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: naloxone; kisspeptin; Hypogonadotropic Hypogonadism
• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Hypogonadism; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Narcotic Antagonists; Naloxone; Prolactin Release-Inhibiting Factors
• Other Study ID Numbers: 313510

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No