Opioid Antagonism in Individuals Ascertained Through the Partners HealthCare Biobank

Study Overview
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Brief Summary
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The goal of this study is to evaluate the effects of opioid antagonists on the hypothalamic-pituitary-gonadal axis in healthy subjects.

Detailed Description
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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 study, the subjects will complete period 1 or periods 1 and 2 Period 1: Undergo frequent blood sampling for up to 13 hours; the total amount of blood drawn during the visit does not exceed maximum blood draw volumes per institutional guidelines Receive up to 3 kisspeptin intravenous (IV) boluses Receive up to 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 up to 3 kisspeptin IV boluses Receive up to 1 GnRH IV bolus

Official Title
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Opioid Antagonism in Individuals Ascertained Through the Partners HealthCare Biobank

Conditions
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Reproductive Disorders

Intervention / Treatment
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* Drug: kisspeptin 112-121
* Drug: GnRH
* Drug: Naloxone


Participation Criteria
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Eligibility Criteria
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Normal puberty with respect to onset and pace No history of chronic disease No prescription medications for at least 2 months except for seasonal allergy medications No illicit drug use No excessive alcohol consumption (< 10 drinks/week) No history of a medication reaction requiring emergency medical care No difficulty with blood draws Not currently seeking fertility Body Mass Index (BMI) > 18.5 and < 30 kg/m2 Normal blood pressure (BP) (systolic BP < 140 mm Hg, diastolic < 90 mm Hg) White blood cell, platelet counts, prolactin, and Thyroid Stimulating Hormone (TSH) between 90% of the lower limit and 110% of the upper limit of the reference range Normal hemoglobin Blood urea nitrogen (BUN), creatinine not elevated Aspartate aminotransferase (AST), alanine transaminase (ALT) <2x upper limit of reference range Normal levels of LH, Follicle Stimulating Hormone (FSH), and sex steroids (estradiol or testosterone) Negative urine drug screening panel For men: Normal erectile and ejaculatory function by report, no history of reproductive disorders (i.e. no history of cryptorchidism) Testicular volume >15 ml by Prader orchidometer For women: Menstrual cycles between 25 and 35 days in duration, at least 11 periods/year, with no more than 5 days variability in cycle duration No oral contraceptives for at least 1 month No evidence for androgen excess (hirsutism or acne) Not breastfeeding and not pregnant Negative serum human chorionic gonadotropin (hCG) pregnancy test at the time of screening, (additional urine pregnancy test will be conducted prior to drug administration)

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: kisspeptin, GnRH, naloxone<br>Arm Description: IV administration of kisspeptin 112-121; six boluses in two up to 13-hour periods. IV administration of GnRH; two boluses in two up to 13-hour periods. IV administration of naloxone; one bolus and an infusion over an up to 13-hour period. | Drug: kisspeptin 112-121<br>* Six IV doses of kisspeptin 112-121<br>* Other names: metastin 45-54;Drug: GnRH<br>* Two IV doses of GnRH<br>* Other names: gonadotropin-releasing hormone;Drug: Naloxone<br>* One bolus and one infusion of naloxone<br>|

What is the study measuring?
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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 | Two 13-hour periods | 

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 | Two 13-hour periods | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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kisspeptin, naloxone