Weekly everolimus and resistance training to boost bone health in postmenopausal women

Resistance Training and Rapamycin to Enhance Bone Formation in Postmenopausal Women

This project will see if a weekly everolimus pill, resistance (strength) training, or both can improve bone formation and muscle function in postmenopausal women aged 60–75.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 148 (estimated)
• Ages: 60 Years to 75 Years
• Sex: Female
• Sponsor: Odense University Hospital (other)
• Drugs / interventions: chemotherapy
• Locations: 2 sites (Bispebjerg, Region Sjælland and 1 other locations)
• Trial ID: NCT07191353 on ClinicalTrials.gov

What this trial studies

Postmenopausal women aged 60–75 with low bone mass (DXA T-score between -1.0 and -2.5) are randomized equally into four groups: weekly everolimus, weekly placebo, everolimus plus thrice-weekly one-hour resistance training, or placebo plus the same training. Participants attend 5–7 visits for blood tests, DXA and MRI scans (HR-pQCT at Odense), muscle and bone biopsies, quality-of-life questionnaires, and muscle function testing. The trial compares changes in bone formation markers, bone density/structure, and muscle function between the groups over the study period. Major exclusions include established osteoporosis, recent low-energy fractures, impaired wound healing, untreated vitamin D deficiency, and conditions limiting weight-bearing exercise.

Who should consider this trial

Good fit: Postmenopausal women aged 60–75 with osteopenia (DXA T-score between -1.0 and -2.5), able to perform resistance exercise, attend multiple clinic visits, and give informed consent are ideal candidates.

Not a fit: Women with osteoporosis (T-score ≤ -2.5), recent low-energy fractures, significant mobility limitations, impaired wound healing, or contraindications to everolimus are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, this approach could increase bone formation and muscle strength in older women, potentially lowering fracture risk and improving mobility.

How similar studies have performed: Resistance training is proven to improve bone and muscle in older adults, but using rapamycin/everolimus to enhance bone formation is novel and supported mainly by preclinical data with limited human evidence.

Eligibility criteria

Inclusion Criteria:

* Women aged 60-75 years old, any ethnicity.
* Participants with T- score between \< 1.0 and \> -2.5 measured by DXA scan within 6 months of the first day of the study.
* Adequate cognitive function to be able to give informed consent.

Exclusion Criteria:

* Osteoporosis and fracture history

  * Participants with osteoporosis (defined by DXA scan \< 6 months old: low bone mass, T-score \< -2.5 or hip fracture or clinical compression fracture of the spine).
  * History of low energy fractures within last 6 months. Health conditions limiting exercise
  * Health conditions that could limit walking and weightbearing exercise (for instance recent surgery, mobility limitation)
  * Participants with impaired wound healing or history of a chronic open wound Bone metabolism disorders
  * Primary hyperparathyroidism.
  * Known vitamin D deficiency (\<25 nM) (re-test after substitution acceptable).
  * Known disorders affecting bone metabolism, e.g., uncontrolled thyrotoxicosis, severe renal impairment (eGFR \< 30) or impaired liver function (baseline phosphatase higher than twice upper limit (105 U/L)), active rheumatic diseases, celiac disease, severe chronic obstructive lung disease (COPD), hypopituitarism, or Cushing's disease.
  * Previous use of bone antiresorptive or bone anabolic drugs within the last 5 years.

Medication use and health conditions

* Use of anabolic steroids in the previous year.
* Use of antiresorptive therapy in the previous year.
* Known medication/supplements affecting bone in the previous year.
* Diabetes type 1 and 2.
* Heart failure similar to NYHA Class IV.
* Treatment with drugs known to affect cytochrome P450 3A due to its role in everolimus metabolism, excluding strong CYP3A4 inhibitors or inducers, while allowing weak and intermediate inhibitors or inducers. Patients on the following drugs will be excluded from the trial: Ketoconazole, Itraconazole, Posaconazole, Voriconazole, Telithromycin, Clarithromycin, Nedazodone, Ritonavir, Atazanavir, Saquinavir, Darunavir, Indinavir, Nelfinavir, Rifampicin, Dexamethasone, Carbamazepine, phenobarbital, Phenytoin, Efavirenz and Nivirapine.
* History of coagulopathy or medical condition requiring long-term anticoagulation.

Blood disorders and other health concerns

* Anemia - Hg \< 5,59 mmol/L, Leukopenia - white blood cells (WBC) \< 3,5 x 10⁹/L, Neutropenia absolute neutrophil count \< 2,0 x 10⁹/L, or Platelet count - platelet count \< 125 x 10⁹/L.
* Insufficiently treated dyslipidemia with LDL-c \> 4,9 mmol/L and family history of dyslipidemia, Total cholesterol \> 9,1 mmol/L, or triglycerides \> 9,9 mmol/L.

Immunosuppressive and current cancer Treatment

* Scheduled for immunosuppressant therapy for transplant or scheduled to undergo chemotherapy or any other treatment for malignancy
* Any form of clinically relevant primary or secondary immune dysfunction or deficiency Cardiovascular and heart conditions
* Unstable ischemic heart disease.

Allergies

* Known allergy to rapamycin or rapalogs. Language limitations
* The study will exclude participants with inability to speak and understand Danish and with inability to cooperate.

Where this trial is running

Bispebjerg, Region Sjælland and 1 other locations

• Institute of Sports Medicine, Bispebjerg Hospital — Bispebjerg, Region Sjælland, Denmark (RECRUITING)
• Department of Endocrinology, Odense University Hospital — Odense, Region Syddanmark, Denmark (RECRUITING)

Study contacts

• Principal investigator: Moustapha Kassem, MD — Odense University Hospital
• Study coordinator: Sofie Elkjær, MD

Conditions: Healthy, Osteopenia, Osteoporosis Risk, Postmenopausal Women, Rapamycin, Bone formation, Muscle functions, Healthy aging