Status:
RECRUITING
Romosozumab as an Adjunct to Physiologic Estrogen Replacement in Functional Hypothalamic Amenorrhea
Lead Sponsor:
Massachusetts General Hospital
Conditions:
FHA (Functional Hypothalamic Amenorrhea)
Eligibility:
FEMALE
14-30 years
Phase:
PHASE3
Brief Summary
The goal of this study is to determine whether romosozumab will improve bone density in girls and women with functional hypothalamic amenorrhea (cessation of the menstrual period due to intense exerci...
Eligibility Criteria
Inclusion
- For FHA and controls:
- Female, age 14-30 years, skeletally mature with bone age ≥ 14 years (only 2% of growth left)
- For women of reproductive age, agree to use an effective non-hormonal contraceptive method or a progestin releasing intrauterine device (no evidence of systemic skeletal effects) or implant for the study duration
- Biochemical criteria:
- Negative βHCG (pregnancy test)
- TSH within twice the upper limit of normal; potassium, magnesium within the normal range; prolactin \<10 ng/mL above the upper limit of normal; FSH not elevated.
- Serum ALT ≤ 3 times upper limit of normal, LDL ≤ 190 mg/dl
- eGFR ≥ 30ml/minute
- If the diagnosis of FHA is unclear, we may check additional labs (e.g., testosterone and sex hormone binding globulin if there is a suspicion of PCOS based on clinical hyperandrogenism).
- Additional inclusion criteria for FHA:
- Less than 3 menses in the preceding 6 months
- BMD Z-score ≤ -1.0 at ≥ 1 skeletal site (for subjects \<18 years old, we will use the height Z-score-adjusted BMD Z-score using the pediatric bone density calculator developed by the National Institutes of Health and currently maintained by the Children's Hospital of Philadelphia)
- Dental check-up within the past year
- If the menstrual status of the subject is unclear due to the presence of a progestin-releasing IUD, serum estradiol levels will be checked twice, at least one week apart. Both estradiol levels must be \< 50 pg/mL.
Exclusion
- For FHA and controls
- Disease other than FHA known to affect bone, including untreated thyroid dysfunction, Cushing's disease, renal failure, diabetes mellitus
- Use of bisphosphonates
- Use of other medications known to affect bone metabolism within 3 months of the study (other than calcium and vitamin D supplementation).
- Current use of systemic corticosteroids
- Migraine with aura.
- Personal history of or first-degree relative with unprovoked thromboembolism (unless the subject has been tested and ruled out for a hypercoagulable state).
- Active substance use disorder; currently smokes or vapes
- History of malignancy or Paget disease of bone
- Pregnant, planning to become pregnant within 12 months after the end of treatment and/or breastfeeding
- Additional exclusion criteria for FHA
- Cardiovascular: History of myocardial infarction or stroke; history of hypertension or use of anti-hypertensive medications
- Immunodeficiency or taking immunosuppressive therapy
- Other conditions that can cause oligo-amenorrhea such as PCOS, primary ovarian insufficiency
- Dental: Osteonecrosis of the jaw (ONJ) or risk factor for ONJ, such as invasive dental procedures (tooth extraction, dental implants, oral surgery in the past 3 months), poor oral hygiene, periodontal and/or pre-existing dental disease
- Planned invasive dental procedure or other planned major surgery for 18 months after the baseline visit
- Known sensitivity or absolute contraindication to any of the products or components of the medications to be administered (romosozumab, zoledronic acid, transdermal estradiol, micronized progesterone, calcium or vitamin D supplements)
- Concerning EKG findings for ischemia
- Additional exclusion criteria for normal-weight healthy controls
- • BMD Z-score \<-2.5 (who we will refer for evaluation)
Key Trial Info
Start Date :
March 19 2025
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
April 1 2029
Estimated Enrollment :
114 Patients enrolled
Trial Details
Trial ID
NCT06533865
Start Date
March 19 2025
End Date
April 1 2029
Last Update
October 20 2025
Active Locations (2)
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1
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
2
University of Virginia Medical Center
Charlottesville, Virginia, United States, 22903