Neuropeptides in Human Reproduction

NCT01952782 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 2013P001543
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hypogonadotropic Hypogonadism

Keywords

Reproductive disorders; Hypogonadotropic hypogonadism; Kisspeptin; GnRH; Naloxone

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

Naloxone, Kisspeptin, GnRH

EXPERIMENTAL

Intravenous (IV) administration of kisspeptin 112-121, GnRH, and naloxone

Drug: Kisspeptin 112-121; Drug: Naloxone; Drug: GnRH

Interventions

Kisspeptin 112-121 DRUG

Subjects will receive up to 10 IV doses of kisspeptin 112-121

Also known as: Metastin 45-54

Naloxone, Kisspeptin, GnRH

Naloxone DRUG

Subjects will receive one IV dose of naloxone followed by an IV infusion of naloxone.

Naloxone, Kisspeptin, GnRH

GnRH DRUG

Subjects will receive up to 10 doses of IV GnRH

Also known as: Gonadotropin-releasing hormone

Naloxone, Kisspeptin, GnRH

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• For healthy men and healthy regularly cycling women: normal
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (2)

• 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.

  PMID: 31132118 DERIVED

• 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.

  PMID: 29669934 DERIVED

MeSH Terms

Conditions

Hypogonadism

Interventions

Naloxone; Gonadotropin-Releasing Hormone

Condition Hierarchy (Ancestors)

Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Stephanie B Seminara, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Reproductive Endocrine Unit; Professor of Medicine, Harvard Medical School; Director, MGH Harvard Center for Reproductive Medicine

Study Record Dates

• First Submitted: September 24, 2013
• First Posted: September 30, 2013
• Study Start: April 30, 2014
• Primary Completion: May 31, 2016
• Study Completion: May 31, 2016
• Last Updated: July 31, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)