Resistance Training and Rapamycin to Enhance Bone Formation in Postmenopausal Women

NCT ID: NCT07191353

Last Updated: 2025-10-01

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 148 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-30
• Study Completion Date: 2027-03-01

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Everolimus

Oral everolimus 5 mg once a week

Group Type: EXPERIMENTAL

Everolimus

Intervention Type: DRUG

Everolimus 5 mg administered once weekly for 24 weeks

Everolimus and resistance training

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

Group Type: EXPERIMENTAL

Everolimus

Intervention Type: DRUG

Everolimus 5 mg administered once weekly for 24 weeks

Resistance training

Intervention Type: OTHER

Resistance training 3 times a week for 24 weeks

Placebo

Oral placebo once a week

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo administered once weekly for 24 weeks

Placebo and resistance training

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo administered once weekly for 24 weeks

Resistance training

Intervention Type: OTHER

Resistance training 3 times a week for 24 weeks

Interventions

Everolimus

Everolimus 5 mg administered once weekly for 24 weeks

Intervention Type: DRUG

Placebo

Placebo administered once weekly for 24 weeks

Intervention Type: DRUG

Resistance training

Resistance training 3 times a week for 24 weeks

Intervention Type: OTHER

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.

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Bispebjerg Hospital

OTHER

Sponsor Role: collaborator

Odense University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Moustapha Kassem, MD

Role: PRINCIPAL_INVESTIGATOR

Odense University Hospital

Locations

Institute of Sports Medicine, Bispebjerg Hospital

Bispebjerg, Region Sjælland, Denmark

Department of Endocrinology, Odense University Hospital

Odense, Region Syddanmark, Denmark

Countries

Denmark

Central Contacts

Sofie Elkjær, MD

Role: CONTACT

anna.sofie.elkjaer3@rsyd.dk

+4521428178

Frederik Marquard, MD

Role: CONTACT

frederik.marquard.nielsen@regionh.dk

Facility Contacts

Frederik M Nielsen, Doctor

Role: primary

frederik.marquard.nielsen@regionh.dk

42802315

Abigail Mackey, Professor

Role: backup

abigailmac@sund.ku.dk

Sofie Elkjær, MD

Role: primary

anna.sofie.elkjaer3@rsyd.dk

+4521428178

Moustapha Kassem, MD, professor

Role: backup

mkassem@health.sdu.dk

+45 24467199

Other Identifiers

2024-520372-10-00

Identifier Type: -

Identifier Source: org_study_id