Reproductive Disorder
Conditions
Keywords
reproductive disorders, kisspeptin, infertility, GnRH
Brief summary
The objective of this protocol is to assess response to kisspeptin and gonadotropin-releasing hormone (GnRH) stimulation testing as well as the baseline patterns of luteinizing hormone (LH) secretion in individuals who carry variants in genes related to infertility.
Detailed description
Assignment: All study subjects will undergo the same interventions. Individuals at high risk for infertility (i.e., carry variants in genes related to infertility) will be compared to controls (i.e., those who do not carry variants in genes related to infertility). Delivery of Interventions: * Prior to the inpatient study visit, the subjects will undergo a review of their medical history, physical exam, and screening laboratories. * On the day of the study, the subjects will have an intravenous (IV) line placed and * Undergo up to q10 min blood sampling x 12 hours * Receive a single kisspeptin IV bolus at hour 8 * Receive a single GnRH IV bolus at hour 11
Interventions
One IV bolus of kisspeptin 112-121
DRUGGnRH
One IV bolus of gonadotropin-releasing hormone
Sponsors
Stephanie B. Seminara, MD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* No prescription medications that could interfere with hypothalamic reproductive function * No illicit drug use * No excessive alcohol consumption (more than 10 drinks/week) * No history of an allergic medication reaction requiring emergency medical care * Normal blood pressure reading (systolic blood pressure \< 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 aminotransferase (ALT) within 3 times upper limit of normal * Enrolled in the Partners HealthCare Biobank and genotypically characterized * For women * No oral contraceptives for at least 1 month * No contraceptive implants for at least 3 months * 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Endogenous LH Pulse Amplitude | Hours 0-8 | Average amplitude of LH pulses at baseline |
| Kisspeptin-induced LH Pulse Amplitude | Hours 8-11 | Amplitude of LH pulse in response to kisspeptin |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORStephanie B Seminara, MD
Massachusetts General Hospital
Participant flow
Recruitment details
Boston area. 16 participants were consented and screened for eligibility between 10/2023 and 4/2024.
Pre-assignment details
There was no washout or run-in period. 4 individuals were found to be ineligible by criteria.
Participants by arm
| Arm | Count |
|---|---|
| Kisspeptin, GnRH IV administration of kisspeptin 112-121; one bolus. IV administration of GnRH; one bolus. | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | Kisspeptin, GnRH |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 16 |
| other Total, other adverse events | 1 / 16 |
| serious Total, serious adverse events | 0 / 16 |
Outcome results
Primary
Endogenous LH Pulse Amplitude
Average amplitude of LH pulses at baseline
Time frame: Hours 0-8
Population: No participants underwent the intervention. This trial was terminated because the study team no longer had access to the study drugs.
Primary
Kisspeptin-induced LH Pulse Amplitude
Amplitude of LH pulse in response to kisspeptin
Time frame: Hours 8-11
Population: No participants underwent the intervention. This trial was terminated because the study team no longer had access to the study drugs.