Resistance Training and Rapamycin to Enhance Bone Formation in Postmenopausal Women

Not Applicable

Not yet recruiting

• Conditions: Healthy; Osteopenia; Osteoporosis Risk
• Interventions: Drug: Everolimus; Drug: Placebo; Other: Resistance training

• Registration Number: NCT07191353
• Lead Sponsor: Odense University Hospital

Brief Summary

The aim of the present clinical trial is to examine the effects of everolimus, resistance training, or their combination on bone and muscle health formation in elderly women aged 60-75 years. The main questions it aims to answer are:

Can rapamycin's analog (Everolimus), resistance training, or their combination, enhance bone formation and muscle functions in elderly women compared to non-treatment controls.

Participants will be randomized 1:1:1:1 to one of the following treatment regimens:

* Oral everolimus 5 mg once a week.

* Oral placebo once a week.

* Oral everolimus 5 mg once a week plus resistance training RT 1 hour, 3 times weekly.

* Oral placebo once a week plus resistance training RT 1 hour, 3 times weekly.

During the study there will be a total of 5-7 visits, where the participants will undergo the following:

* Blood samles

* DXA-, HRpQCT- (only Odense Universitetshospital) and MRI-scans

* Muscle- and bone biopsies

* Quality of life questionnaires

* Testing of muscle funtion

* Metabolic studies of muscle and bone protein turnover using labelling with deuturated water

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-09
• Study First Submitted: 2025-09-09
• Study First Submitted QC: 2025-09-17
• Study First Posted: 2025-09-24
• Study Start: 2025-09-30
• Last Update Submitted: 2025-09-30
• Last Update Posted: 2025-10-01
• Primary Completion: 2027-03-01
• Study Completion: 2027-03-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 148

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Everolimus	Everolimus	Oral everolimus 5 mg once a week
Everolimus and resistance training	Everolimus	Oral everolimus 5 mg once a week plus resistance training RT 1 hour, 3 times weekly
Everolimus and resistance training	Resistance training	Oral everolimus 5 mg once a week plus resistance training RT 1 hour, 3 times weekly
Placebo	Placebo	Oral placebo once a week
Placebo and resistance training	Placebo	Oral placebo once a week plus resistance training RT 1 hour, 3 times weekly
Placebo and resistance training	Resistance training	Oral placebo once a week plus resistance training RT 1 hour, 3 times weekly

Primary Outcome Measures

Name	Time	Method
P1NP	From baseline to end of treatment at 24 weeks	Percentage change in circulating levels of bone formation marker N-terminal fragment of procollagen type 1 (P1NP) at 24 weeks as compared with baseline

Secondary Outcome Measures

Name	Time	Method
Bone resorption markers	From baseline to end of treatment 24 weeks	Change in bone resorption markers (C-terminal telopeptide of type 1 collagen (CTX) at baseline, 4, 12 and 24 weeks.
BMD	From screening to end of treatment 24 weeks	Lumbar spine (L1-4), and total hip and femoral neck bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) at screening visit/baseline, and 24 weeks.
Bone mass	From baseline to end of treatment 24 weeks	Bone mass at the distal radius and tibia measured using high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline, and 24 weeks.
Bone microarchitecture	From baseline to end of treatment 24 weeks	Bone microarchitecture at the distal radius and tibia measured using high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline, and 24 weeks.
Bone geometry	From baseline to end of treatment (24 weeks)	Bone geometry at the distal radius and tibia measured using high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline and 24 weeks.
Muscle Cross-Sectional Area	From baseline to end of treatment 24 weeks	Muscle Cross-Sectional Area (CSA) measured by Magnetic Resonance Imaging (MRI) at baseline, 12, and 24 weeks.
Muscle assessment	From baseline to end of treatment 24 weeks	Change in muscle strength for the lower extremities, measured using a isokinetic dynamometry at baseline, midway and week 24.
Metabolic health (test 1)	From baseline to end of treatment 24 weeks	Body weight measured by a digital scale at baseline, 4, 12, and 24 weeks.
Quality of life quiestionaire	From baseline to end of treatment 24 weeks	Quality of life (QoL)questionnaire SF-12 questionnaire (including mental QoL and physical QoL, and various health and possible side effects) at baseline and 24 weeks
Muscle function (power)	From baseline to end of treatment 24 weeks.	Muscle function (power) using the 30-second sit-to-stand test (RSS) at baseline, midway and week 24.
Bone formation markers	From baseline to end of study 24 weeks	P1NP at baseline, 4 and 12 and 24 weeks.
Metabolic health (test 2)	From screening to end of treatment 24 weeks	Total body fat percentage assessed by dual-energy X-ray absorptiometry (DXA), at screening and 24 weeks.
Metabolic health (test 3)	From baseline to end of treatment 24 weeks	Lipid parameters (LDL, HDL, Triglycerides, Cholesterol) at baseline, 4, 12, and 24 weeks
Metabolic Health (Test 4)	From screening to end treatment	Total lean mass assessed by dual-energy X-ray absorptiometry (DXA) screening and baseline, and 24 weeks.
Metabolic health (test 5)	From screening to end of treatment 24 weeks	Bone mineral density assessed by dual-energy X-ray absorptiometry (DXA) at screening and 24 weeks.

Trial Locations

Locations (2)

Department of Endocrinology, Odense University Hospital; 🇩🇰 Odense, Region Syddanmark, Denmark

Institute of Sports Medicine, Bispebjerg Hospital; 🇩🇰 Bispebjerg, Region Sjælland, Denmark