Romosozumab as an Adjunct to Physiologic Estrogen Replacement in Functional Hypothalamic Amenorrhea
- Conditions
- FHA (Functional Hypothalamic Amenorrhea)
- Interventions
- Registration Number
- NCT06533865
- Lead Sponsor
- Massachusetts General Hospital
- 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 exercise, stress, or an eating disorder) who have low bone density. Participants will be randomly assigned to receive romosozumab or placebo for 6 months. All participants will receive one IV infusion of zoledronate at the 6 month visit. All participants will also receive transdermal estradiol and cyclic progesterone. We will investigate whether participants who receive active romosozumab will demonstrate greater improvements in bone density at one year than those who receive placebo. We will also compare bone density over a year with healthy controls (girls and women of similar age who have regular menstrual periods).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 114
For FHA and controls:
- Female, age 14-25 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) for the study duration
- Biochemical criteria:
- Negative βHCG (pregnancy test)
- TSH, 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
- Dental check-up within the past year
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).
- 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; current smoker
- 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, and current use of corticosteroids
- Planned invasive dental procedure or other planned major surgery over the next 12 months (the duration of the study)
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Romosozumab Romosozumab Participants with functional hypothalamic amenorrhea randomized to romosozumab. Romosozumab Zoledronic acid Participants with functional hypothalamic amenorrhea randomized to romosozumab. Placebo Placebo Participants with functional hypothalamic amenorrhea randomized to placebo. Placebo Zoledronic acid Participants with functional hypothalamic amenorrhea randomized to placebo.
- Primary Outcome Measures
Name Time Method Tibial cortical thickness 0 and 6 months 6-month change in tibial cortical thickness
Lumbar spine bone density 0 and 6 months 6-month change in lumbar spine bone density
Tibial failure load 0 and 6 months 6-month change in tibial failure load
- Secondary Outcome Measures
Name Time Method Femoral neck and total hip bone density 0, 6, and 12 months 6- and 12-month change in femoral neck and total hip bone density
Tibial failure load 0 and 12 months 12-month change in change in tibial failure load
Tibial cortical thickness 0 and 12 months 12-month change in tibial cortical thickness
Lumbar spine, femoral neck, and total hip bone density 0, 6, and 12 months 6- and 12-month in lumbar spine, femoral neck, and total hip bone density
Lumbar spine bone density 0 and 12 months 12-month change in lumbar spine bone density
P1NP and CTX 0, 1, 6 and 12 months 1-, 6- and 12-month change in markers of bone metabolism
Radial failure load 0, 6, and 12 months 6- and 12-month change in radial failure load
Tibial and radial cortical thickness 0, 6 and 12 months 6- and 12-month change in tibial and radial cortical thickness
Tibial and radial failure load 0, 6 and 12 months 6- and 12-month change in tibial and radial failure load
Radial cortical thickness 0, 6, and 12 months 6- and 12-month change in radial cortical thickness
Trial Locations
- Locations (2)
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of Virginia Medical Center
🇺🇸Charlottesville, Virginia, United States