Neuropeptides in Human Reproduction
Primary Purpose
Hypogonadotropic Hypogonadism
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Kisspeptin 112-121
Naloxone
GnRH
Sponsored by
About this trial
This is an interventional other trial for Hypogonadotropic Hypogonadism focused on measuring Reproductive disorders, Hypogonadotropic hypogonadism, Kisspeptin, GnRH, Naloxone
Eligibility Criteria
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:
- 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
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
Sites / Locations
- Massachusetts General HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Naloxone, Kisspeptin, GnRH
Arm Description
Intravenous (IV) administration of kisspeptin 112-121, GnRH, and naloxone
Outcomes
Primary Outcome Measures
Average difference in luteinizing hormone (LH) concentration before and after kisspeptin
Compares response to kisspeptin on and off naloxone infusion
Secondary Outcome Measures
Full Information
NCT ID
NCT01952782
First Posted
September 24, 2013
Last Updated
July 17, 2023
Sponsor
Massachusetts General Hospital
1. Study Identification
Unique Protocol Identification Number
NCT01952782
Brief Title
Neuropeptides in Human Reproduction
Official Title
Neuropeptides in Human Reproduction
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 30, 2014 (Actual)
Primary Completion Date
August 2025 (Anticipated)
Study Completion Date
August 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
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 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypogonadotropic Hypogonadism
Keywords
Reproductive disorders, Hypogonadotropic hypogonadism, Kisspeptin, GnRH, Naloxone
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
128 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Naloxone, Kisspeptin, GnRH
Arm Type
Experimental
Arm Description
Intravenous (IV) administration of kisspeptin 112-121, GnRH, and naloxone
Intervention Type
Drug
Intervention Name(s)
Kisspeptin 112-121
Other Intervention Name(s)
Metastin 45-54
Intervention Description
Subjects will receive up to 10 IV doses of kisspeptin 112-121
Intervention Type
Drug
Intervention Name(s)
Naloxone
Intervention Description
Subjects will receive one IV dose of naloxone followed by an IV infusion of naloxone.
Intervention Type
Drug
Intervention Name(s)
GnRH
Other Intervention Name(s)
Gonadotropin-releasing hormone
Intervention Description
Subjects will receive up to 10 doses of IV GnRH
Primary Outcome Measure Information:
Title
Average difference in luteinizing hormone (LH) concentration before and after kisspeptin
Description
Compares response to kisspeptin on and off naloxone infusion
Time Frame
Within 30 minutes of administration
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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:
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
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Study Coordinator
Phone
617-643-2308
Email
MGHKisspeptinResearch@partners.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephanie B 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
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
617-643-2308
Email
MGHKisspeptinResearch@partners.org
First Name & Middle Initial & Last Name & Degree
Stephanie B Seminara, MD
First Name & Middle Initial & Last Name & Degree
Yee-Ming Chan, MD, PhD
First Name & Middle Initial & Last Name & Degree
Margaret Lippincott, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
31132118
Citation
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.
Results Reference
derived
PubMed Identifier
29669934
Citation
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.
Results Reference
derived
Learn more about this trial
Neuropeptides in Human Reproduction
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