Clinical trial NCT01952782: Neuropeptides in Human Reproduction
Official title: Neuropeptides in Human Reproduction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypogonadotropic Hypogonadism
Keywords: Reproductive disorders
Hypogonadotropic hypogonadism
Kisspeptin
GnRH
Naloxone
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2013-09-30
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.


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:

  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

Primary outcomes:
measure: Average difference in luteinizing hormone (LH) concentration before and after kisspeptin
timeFrame: Within 30 minutes of administration
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Stephanie B Seminara, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.