Back to resultsOpioid Antagonism in Hypogonadotropic Hypogonadism
Primary Purpose
Hypogonadotropic Hypogonadism
Status
Enrolling by invitation
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
kisspeptin, GnRH, naloxone
GnRH
Naloxone
Sponsored by
About this trial
This is an interventional treatment trial for Hypogonadotropic Hypogonadism focused on measuring Hypogonadotropic Hypogonadism, kisspeptin, naloxone
Eligibility 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
Sites / Locations
- Massachusetts General Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
kisspeptin, GnRH, naloxone
Arm Description
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.
Outcomes
Primary Outcome Measures
Average change in Luteinizing Hormone (LH) pulse frequency
Change in LH pulse frequency before and during naloxone infusion
Secondary Outcome Measures
Average change in LH pulse amplitude
change in LH pulse amplitude before and during naloxone infusion
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04975334
Brief Title
Opioid Antagonism in Hypogonadotropic Hypogonadism
Official Title
Opioid Antagonism in Hypogonadotropic Hypogonadism
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Enrolling by invitation
Study Start Date
December 31, 2023 (Anticipated)
Primary Completion Date
May 31, 2025 (Anticipated)
Study Completion Date
May 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Stephanie B. Seminara, MD
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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).
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypogonadotropic Hypogonadism
Keywords
Hypogonadotropic Hypogonadism, kisspeptin, naloxone
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
kisspeptin, GnRH, naloxone
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
kisspeptin, GnRH, naloxone
Other Intervention Name(s)
metastin 45-54
Intervention Description
Six IV doses of kisspeptin 112-121
Intervention Type
Drug
Intervention Name(s)
GnRH
Other Intervention Name(s)
gonadotropin-releasing hormone
Intervention Description
Two IV doses of GnRH
Intervention Type
Drug
Intervention Name(s)
Naloxone
Intervention Description
One bolus and one infusion of naloxone
Primary Outcome Measure Information:
Title
Average change in Luteinizing Hormone (LH) pulse frequency
Description
Change in LH pulse frequency before and during naloxone infusion
Time Frame
Before and during treatment
Secondary Outcome Measure Information:
Title
Average change in LH pulse amplitude
Description
change in LH pulse amplitude before and during naloxone infusion
Time Frame
Before and during treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephanie Seminara, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Opioid Antagonism in Hypogonadotropic Hypogonadism
We'll reach out to this number within 24 hrs