Hypogonadotropic Hypogonadism
Conditions
Keywords
hypogonadotropic hypogonadism, kisspeptin
Brief summary
The goal of this study is to develop novel treatments for patients with a condition called hypogonadotropic hypogonadism (HH) through the use of exogenous kisspeptin.
Detailed description
* Assignment: Each study subject will serve as their own control. The order of kisspeptin doses will be randomized within each set/exposure. * Delivery of Interventions: * Prior to the study visit, subjects will undergo a review of their medical history and screening laboratories. Subjects will also wear a gonadotropin releasing hormone (GnRH) pump prior to the inpatient study visit. * On the day of the inpatient study, the subjects will * Undergo q10 min blood sampling for 6 hours, * Receive kisspeptin intravenous (IV) boluses from hour 6 to hour 44 (20 boluses total), * Undergo q10 min blood samplings for another 6 hours, * Receive a single GnRH IV bolus at hour 51.
Interventions
20 intravenous doses of kisspeptin 112-121 (4 different doses of kisspeptin (randomized) in 5 sets)
DRUGGnRH
1 intravenous dose of GnRH
Sponsors
Stephanie B. Seminara, MD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion/
Exclusion criteria
* Age 18 years and older, * Confirmed diagnosis of HH with * Low testosterone or estradiol, * Low or low-normal gonadotropin levels, * Thyroid stimulating hormone (TSH) and prolactin within the reference range, * Absence of abnormal pituitary or hypothalamic findings on Magnetic resonance imaging (MRI), * All other medical conditions stable and well controlled, * No prescription medications known to affect reproductive endocrine function for at least 2 months or for 5 half-lives of the drug (whichever is shorter) except for medications used to treat the subject's reproductive condition, * No history of a medication reaction requiring emergency medical care, * No illicit drug use, * No excessive alcohol consumption (\<10 drinks/week), * Normal blood pressure (BP), (systolic BP \< 140 mm Hg, diastolic \< 90 mm Hg), * White blood cell, platelet counts, and TSH between 90% of the lower limit and 110% of the upper limit of the reference range, * Prolactin below 110% of the upper limit of the reference range, * Hemoglobin * Women: no less than 0.5 gm/dL below the lower limit of the reference range for normal women, * Men: on adequate testosterone replacement therapy: normal male reference range, * Blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (AST), alanine transaminase (ALT) not elevated, * For women, * Negative serum human chorionic gonadotropin (hCG) pregnancy test at the time of screening (additional urine pregnancy test will be conducted prior to drug administration), * Not breastfeeding and not pregnant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Change in Luteinizing Hormone (LH) Pulse Amplitude in Response to Kisspeptin | 52 hours | Change in LH amplitude before, during and after kisspeptin administration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Change in LH Pulse Frequency in Response to Kisspeptin | 52 hours | Change in LH frequency before and after kisspeptin administration |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORStephanie Seminara
Massachusetts General Hospital
Participant flow
Recruitment details
Boston area. 18 participants were consented and screened for eligibility between 5/2019 and 11/2022.
Pre-assignment details
There was no washout or run-in period. All participants were assigned to the same arm.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 2 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 18 |
| other Total, other adverse events | 6 / 18 |
| serious Total, serious adverse events | 1 / 18 |
Outcome results
None listed