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FHA (Functional Hypothalamic Amenorrhea)Phase 3NCT06533865

Romosozumab as an Adjunct to Physiologic Estrogen Replacement in Functional Hypothalamic Amenorrhea

A Phase 3 study testing Romosozumab and Zoledronic acid in people with FHA (Functional Hypothalamic Amenorrhea), run by Massachusetts General Hospital at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 14 to 30 years, women only
Conditions the study is for
FHA (Functional Hypothalamic Amenorrhea)
What is being tested?
Romosozumab and Zoledronic acid
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
114 participants
Where
2 sitesUnited States
Study dates
19 Mar 2025to Apr 2029
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 14 to 30 years
  • Women only
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • For FHA and controls:
  • Female, age 14-30 years, skeletally mature with bone age ≥ 12 years
  • For women of reproductive age, agree to use one of the following for the study duration:
  • an effective non-hormonal contraceptive method
  • a progestin releasing intrauterine device (no evidence of systemic skeletal effects)
  • a progestin releasing implant
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  • does not have a history of sexual activity that could lead to pregnancy (i.e., same-sex partners only or total abstinence has been and is their preferred lifestyle)
  • 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.At the discretion of the study clinician, subjects with a diagnosis of PCOS may undergo one to two serum estradiol levels, at least one week apart. The estradiol level(s) must be < 50 pg/mL

Who cannot join

  • 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 in the past year
  • 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 as classified in IHS Classification ICHD-3.
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  • 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. A participant with PCOS may be included if a study clinician determines that missed menstrual periods are more likely a consequence of FHA.
  • 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)

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Karen K Miller, MD contact

617-726-3870

kkmiller@mgh.harvard.edu

Melanie Haines, MD contact

617-726-3897

mshaines@mgh.harvard.edu

United States2 sites, 2 recruiting

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

    Karen Miller, MD, 617-726-3870, kkmiller@mgh.harvard.edu

    Melanie Haines, MD, 617-726-3897, mshaines@mgh.harvard.edu

    Recruiting

  • University of Virginia Medical Center

    Charlottesville, Virginia, 22903

    Madhusmita Misra, MD, MPH, 434-924-9141, ABP6BD@uvahealth.org

    Andrea Marrs, MS, 434-982-0871, misralab@uvahealh.org

    Recruiting

Other trials in United States

About this study

Official title: Romosozumab as an Adjunct to Physiologic Estrogen Replacement in Adolescents and Young Adults With Functional Hypothalamic Amenorrhea

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).

Being tested
Romosozumab, Placebo, Zoledronic acid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RomosozumabDrug

    Also called Evenity

    Six monthly subcutaneous injections. This group will also receive a 100-microgram transdermal estradiol patch applied twice weekly, and 200 mg of oral progesterone for the first 12 days of each month.

  • PlaceboDrug

    Identical to romosozumab but inactive. This group will also receive a 100-microgram transdermal estradiol patch applied twice weekly, and 200 mg of oral progesterone for the first 12 days of each month.

  • Zoledronic acidDrug

    Also called Zoledronate, Reclast

    One intravenous infusion

Study groups in NCT06533865
Study groupRoleWhat they receive
RomosozumabExperimentalParticipants with functional hypothalamic amenorrhea randomized to romosozumab.
Receives: Drug: Romosozumab; Drug: Zoledronic acid
PlaceboPlacebo comparatorParticipants with functional hypothalamic amenorrhea randomized to placebo.
Receives: Drug: Placebo; Drug: Zoledronic acid
Healthy ControlsNo interventionHealthy controls (girls and women with regular menstrual periods)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Lumbar spine bone density

    6-month change in lumbar spine bone density

    Measured: 0 and 6 months

  2. Tibial cortical thickness

    6-month change in tibial cortical thickness

    Measured: 0 and 6 months

  3. Tibial failure load

    6-month change in tibial failure load

    Measured: 0 and 6 months

Secondary outcomes (11)

  1. Femoral neck and total hip bone density

    6- and 12-month change in femoral neck and total hip bone density

    Measured: 0, 6, and 12 months

  2. Lumbar spine bone density

    12-month change in lumbar spine bone density

    Measured: 0 and 12 months

  3. Radial cortical thickness

    6- and 12-month change in radial cortical thickness

    Measured: 0, 6, and 12 months

  4. Tibial cortical thickness

    12-month change in tibial cortical thickness

    Measured: 0 and 12 months

  5. P1NP and CTX

    1-, 6-, and 12-month change in P1NP and CTX

    Measured: 0, 1, 6, and 12 months

  6. Radial failure load

    6- and 12-month change in radial failure load

    Measured: 0, 6, and 12 months

  7. Tibial failure load

    12-month change in change in tibial failure load

    Measured: 0 and 12 months

  8. Lumbar spine, femoral neck, and total hip bone density

    6- and 12-month in lumbar spine, femoral neck, and total hip bone density

    Measured: 0, 6, and 12 months

  9. P1NP and CTX

    1-, 6- and 12-month change in markers of bone metabolism

    Measured: 0, 1, 6 and 12 months

  10. Tibial and radial cortical thickness

    6- and 12-month change in tibial and radial cortical thickness

    Measured: 0, 6 and 12 months

  11. Tibial and radial failure load

    6- and 12-month change in tibial and radial failure load

    Measured: 0, 6 and 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Aug 2024
  2. Study start19 Mar 2025
  3. Primary completionOct 2028 (estimated)
  4. Study completionApr 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
114 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06533865
Sponsor's protocol ID
2024P000273
Status last verified
Apr 2026
First submitted
30 Jul 2024
Last updated
23 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Romosozumab and Zoledronic acid in people with FHA (Functional Hypothalamic Amenorrhea), run by Massachusetts General Hospital at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 23 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Karen K Miller, MD (617-726-3870, kkmiller@mgh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Lumbar spine bone density (time frame: 0 and 6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06533865.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2026.

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