Resistance Training and Rapamycin to Enhance Bone Formation in Postmenopausal Women

NCT07191353 | Not Yet Recruiting Phase 2

• 1 other identifier: 2024-520372-10-00
• Study Type: interventional
• Target: 148
• Locations: 1 country
• Sites: 2

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

Conditions

Healthy; Osteopenia; Osteoporosis Risk

Keywords

Postmenopausal Women; Rapamycin; Bone formation; Muscle functions; Healthy aging

Outcome Measures

Primary Outcomes (1)

• P1NP

  Percentage change in circulating levels of bone formation marker N-terminal fragment of procollagen type 1 (P1NP) at 24 weeks as compared with baseline

  From baseline to end of treatment at 24 weeks

Secondary Outcomes (15)

• Bone resorption markers

  From baseline to end of treatment 24 weeks

• BMD

  From screening to end of treatment 24 weeks

• Bone mass

  From baseline to end of treatment 24 weeks

• Bone microarchitecture

  From baseline to end of treatment 24 weeks

• Bone geometry

  From baseline to end of treatment (24 weeks)

Other Outcomes (6)

• Biomarkers of biological aging

  From baseline to end of treatment 24 weeks

• Epigenetic clocks

  From baseline to end of treatment 24 weeks

• Bone changes

  At the end of the study 24 weeks

Study Arms (4)

Everolimus

EXPERIMENTAL

Oral everolimus 5 mg once a week

Drug: Everolimus

Everolimus and resistance training

EXPERIMENTAL

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

Drug: Everolimus; Other: Resistance training

Placebo

PLACEBO COMPARATOR

Oral placebo once a week

Drug: Placebo

Placebo and resistance training

PLACEBO COMPARATOR

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

Drug: Placebo; Other: Resistance training

Interventions

Everolimus DRUG

Everolimus 5 mg administered once weekly for 24 weeks

Everolimus; Everolimus and resistance training

Placebo DRUG

Placebo administered once weekly for 24 weeks

Placebo; Placebo and resistance training

Resistance training OTHER

Resistance training 3 times a week for 24 weeks

Everolimus and resistance training; Placebo and resistance training

Eligibility Criteria

• Age: 60 Years - 75 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Odense University Hospital: lead
• Bispebjerg Hospital: collaborator

Study Sites (2)

Institute of Sports Medicine, Bispebjerg Hospital

Bispebjerg, Region Sjælland, 2200, Denmark

Location

Department of Endocrinology, Odense University Hospital

Odense, Region Syddanmark, 5000, Denmark

Location

MeSH Terms

Conditions

Bone Diseases, Metabolic

Interventions

Everolimus; Resistance Training

Condition Hierarchy (Ancestors)

Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Physical Therapy Modalities; Physical Conditioning, Human; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Moustapha Kassem, MD

  Odense University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sofie Elkjær, MD

CONTACT

+4521428178; anna.sofie.elkjaer3@rsyd.dk

Frederik Marquard, MD

CONTACT

frederik.marquard.nielsen@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Treatment allocation to rapamycin or placebo is double-blinded, while allocation to training or no training will be known to participants and investigators, but masked to the statistician.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase 2, two-parallel, randomized, placebo-controlled clinical trial

Study Record Dates

• First Submitted: September 9, 2025
• First Posted: September 24, 2025
• Study Start: September 30, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

DK (2)