Neuropeptides in Human Reproduction

The investigators are seeking healthy volunteers and volunteers with reproductive disorders for the study of the role of dynorphin in the reproductive system. Dynorphin is a naturally occurring opioid hormone that is blocked by naloxone.

We hypothesize that naloxone, by blocking dynorphin, will stimulate production of gonadotropin-releasing hormone (GnRH) and kisspeptin, two other naturally occurring reproductive hormones.

Study Overview

• Status: Recruiting
• Conditions: Hypogonadotropic Hypogonadism
• Intervention / Treatment: Drug: Kisspeptin 112-121; Drug: Naloxone; Drug: GnRH

• Study Type: Interventional
• Enrollment (Estimated): 128
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Study Coordinator; Phone Number: 617-643-2308; Email: MGHKisspeptinResearch@partners.org

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Principal Investigator: Stephanie B Seminara, MD
      • Sub-Investigator: Yee-Ming Chan, MD, PhD
      • Sub-Investigator: Margaret Lippincott, MD
      • Contact: Study Coordinator; Phone Number: 617-643-2308; Email: MGHKisspeptinResearch@partners.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Ages 21-40 (healthy men and regularly cycling women) OR ages 18-75 (men and women with hypogonadotropic hypogonadism (HH))
• Normal blood pressure (systolic BP <140 mm Hg, diastolic BP <90 mm Hg)
• White blood cell, platelets, prolactin, and thyroid stimulating hormone (TSH)within 90%-110% of laboratory reference range
• Negative urine drug screen panel

• Hemoglobin:

  1. For healthy men and healthy regularly cycling women: normal
  2. For men and women with HH: No less than 0.5 gm/dL below the lower limit of the reference range for normal women
• Blood urea nitrogen (BUN), creatinine, liver function tests not elevated
• For healthy subjects: Normal reproductive function and history
• For healthy subjects: Body Mass Index (BMI) 18.5-30kg/m2
• For subjects with HH: All medical conditions stable and well controlled

Exclusion Criteria:

• History of medication reaction requiring emergency medical attention
• Illicit drug use
• Consumption of more than 10 alcoholic drinks per week
• Difficulty with blood draws
• Currently seeking fertility, breastfeeding, or pregnant
• For healthy subjects: history of chronic disease and prescription medication use (with the exception of seasonal allergy medication)
• For subjects with HH: prescription medications known to affect reproductive endocrine function except for those used to treat the subject's reproductive condition

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• 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: Naloxone, Kisspeptin, GnRH; Intravenous (IV) administration of kisspeptin 112-121, GnRH, and naloxone	Drug: Kisspeptin 112-121; Subjects will receive up to 10 IV doses of kisspeptin 112-121; Other Names: Metastin 45-54; Drug: Naloxone; Subjects will receive one IV dose of naloxone followed by an IV infusion of naloxone.; Drug: GnRH; Subjects will receive up to 10 doses of IV GnRH; Other Names: Gonadotropin-releasing hormone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average difference in luteinizing hormone (LH) concentration before and after kisspeptin	Compares response to kisspeptin on and off naloxone infusion	Within 30 minutes of administration

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Lippincott MF, Leon S, Chan YM, Fergani C, Talbi R, Farooqi IS, Jones CM, Arlt W, Stewart SE, Cole TR, Terasawa E, Hall JE, Shaw ND, Navarro VM, Seminara SB. Hypothalamic Reproductive Endocrine Pulse Generator Activity Independent of Neurokinin B and Dynorphin Signaling. J Clin Endocrinol Metab. 2019 Oct 1;104(10):4304-4318. doi: 10.1210/jc.2019-00146.
• Chan YM, Lippincott MF, Kusa TO, Seminara SB. Divergent responses to kisspeptin in children with delayed puberty. JCI Insight. 2018 Apr 19;3(8):e99109. doi: 10.1172/jci.insight.99109. eCollection 2018 Apr 19.

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2014
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: September 24, 2013
• First Submitted That Met QC Criteria: September 24, 2013
• First Posted (Estimated): September 30, 2013

Study Record Updates

• Last Update Posted (Actual): July 19, 2023
• Last Update Submitted That Met QC Criteria: July 17, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Naloxone; Kisspeptin; GnRH; Hypogonadotropic hypogonadism; Reproductive disorders
• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Hypogonadism; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Naloxone
• Other Study ID Numbers: 2013P001543

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