Physician, PhD-student
Moustapha Kassem
Department of Endocrinology, Odense University Hospital
| Project management | ||
| Project status | Open | |
| Data collection dates | ||
| Start | 15.10.2024 | |
| End | 01.11.2026 | |
Targeting mTOR with everolimus and/or physical training for preventing postmenopausal bone loss and accelerated skeletal aging. The RapaLoad study.
Short summary
This randomized clinical trial aims to determine if treatment with everolimus, exercise training, or their combination for 24 weeks enhances bone formation in healthy postmenopausal women. A total of 136 healthy postmenopausal women will be randomly assigned to one of four groups: one receiving everolimus once a week, one participating in football fitness training twice a week, one combining both treatments and a control group receiving no treatment for 24 weeks.
Rationale
Menopause is a significant event in women's life as it initiates a series of pathophysiological changes that increase the risk for age related diseases including loss of bone mass and thus are at a higher risk for osteoporotic bone fracture. Therapy with sex hormone replacement has been used to reduce the negative effects of menopause, but it is not widely used in clinical practice due to potential side effects. Hence, there is a need for developing alternative strategies for decreasing the rate of aging in postmenopausal women. Preclinical studies have demonstrated that treatment with rapamycin, an inhibitor of the mechanistic target of rapamycin (mTOR), extends healthspan and lifespan. However, the effects on the musculoskeletal system in humans are not known. Additionally, studies have demonstrated that exercise training improves bone mass and prevents bone loss in postmenopausal women. Football training has a documented positive effect on bone mass and earlier clinical studies suggest that effects of pharmacological interventions on musculoskeletal health can be enhanced if a person is physically active while taking the drug. Hence, combining rapamycin treatment with exercise is attractive for clinical translation since it is expected that this combination leads to synergistic effects on musculoskeletal health. The aim of this study is to conduct a randomized trial of the effect of everolimus, physical training and the combination of both on bone and muscle health in healthy postmenopausal women.
Description of the cohort
This trial will include 136 postmenopausal women (evidenced by measuring serum levels of LH and FSH and absence of menstruation for at least 1 year) aged 45-60 years and no history of low energy hip or vertebral fractures during the last 6 months.
Data and biological material
We use biomarkers for bone formation and bone resorption measured in fasting blood samples. Bone mass assessed using DXA-scan and HRpQCT. Fitness test to evaluate muscle function and cardiopulmonary function.
Collaborating researchers and departments
Department of Sports Science and Clinical Biomechanics, University of Southern Denmark