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NCT Number: NCT06789900

Everolimus and/or Exercise to Prevent Bone Loss in Postmenopausal Women

It is estimated that women lose around 20-25% of bone mass during the 5-10 years period of postmenopausal transition, and menopause is considered a major risk factor for osteoporotic fragility fracture. Currently, there is no preventive strategy to counteract these changes, and hormone replacement therapy is not considered an attractive option for many women, because of concerns related to side effects. Rapamycin, through inhibition of mTOR (the mechanistic target of Rapamycin) has been demonstrated in many preclinical animal models to extend lifespan and healthspan. The most well-established mTOR inhibitors include rapamycin (sirolimus) and its analog (also referred as rapalog). Everolimus are FDA approved and have been used for many years at a high dose as an immunosuppressant and anti-cancer drug. Exercise training has been demonstrated to counteract age-related degenerative changes in several clinical studies. The aim of this randomized clinical trial is to test the effects of treatment with oral Everolimus, exercise, or their combination as a preventive strategy for impaired musculoskeletal function in healthy postmenopausal women.

The trial will include 136 women aged 45-60 years with T-score >-3 and no history of hip, Colles' or symptomatic vertebral fractures within the last 6 months, randomized to 24 weeks of treatment with one of the following regimens:

1. control group getting general health advice, 2. Football fitness session group, physical training consisting of structured hybrid exercise training via the "football fitness concept" for 1hour, 2 times/ week 3. Everolimus group receiving an oral dosage of 5 mg everolimus once a week, (4) Everolimus and football fitness session group, consisting of structured hybrid exercise training via the "football fitness concept" for 1 hour, 2 times/week combined with oral everolimus 5 mg once a week.

The primary outcome of this trial is percentage change in bone formation marker P1NP (Procollagen Type 1 propeptide) between baseline and week 24. Secondary outcomes include percentage changes in bone resorption marker CTX (cross-lined C-telopeptide of type 1 collagen), bone mineral density (BMD), bone structure as determined by high resolution CT-scanning, muscle function and postural balance. As exploratory endpoints, changes in biological age as determined by "epigenetic clocks", levels of senescence-associated secretory phenotype (SASP) as an indicator of whole-body burden of senescent cells.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Postmenopausal Women Behavior Bone Diseases Bone Diseases, Metabolic Metabolic Diseases Motor Activity Musculoskeletal Diseases Nutritional and Metabolic Diseases

Age range

45 year–60 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 2

Primary location

Odense University Hospital

Odense, 5000, Denmark

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Postmenopausal women aged 45-60 years old as evidenced by measuring serum levels of LH and FSH and absence of menstruation for at least 1 year.
  • No history of low energy hip or vertebral fractures during the last 6 months.
  • Ability to provide informed consent.

Exclusion criteria

  • Diabetes (type 1 and 2)
  • Heart failure similar to NYHA Class IV
  • Primary hyperparathyroidism
  • Known disorders affecting bone metabolism, e.g., uncontrolled thyrotoxicosis, severe renal impairment (eGFR <20) or 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.
  • Use of anabolic steroids in the previous year
  • Treatment with drugs known to affect cytochrome P450 3A due to its role in everolimus metabolism
  • History of coagulopathy or medical condition requiring long-term anticoagulation
  • Anemia - Hg < 9.0 g/dl, Leukopenia - white blood cells (WBC) < 3,500/mm3, Neutropenia absolute neutrophil count < 2,000/mm3, or Platelet count - platelet count < 125,000/mm3
  • Patients with impaired wound healing or history of a chronic open wound
  • Scheduled for immunosuppressant therapy for transplant or scheduled to undergo chemotherapy or any other treatment for malignancy
  • Untreated 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
  • Any form of clinically relevant primary or secondary immune dysfunction or deficiency
  • Unstable ischemic heart disease
  • Bone mineral density (BMD) measured by DXA scanning with T-score <-3
  • Known allergy to rapamycin or rapalogs
  • The study will exclude participants with inability to speak and understand Danish and with inability to cooperate or perform physical training.
  • Inability to give informed consent

Treatment and study plan

Everolimus (Afinitor®)

Drug

Oral dose of everolimus 5 mg once a week for 24 weeks

Other names: Football fitness session

Football Fitness Concept

Other

Structured hybrid exercise training via the "football fitness concept" organized as a super-vised group training at the University of Southern Denmark, Department of Sports Science and Clinical Biomechanics. "Football Fitness concept" is designed for participants with little prior experience with football and it is multifaceted training incorporating endurance training, high-intensity interval training (HIIT) and strength training. The training session lasts 60 minutes, and participants will receive two training sessions per week for 24 weeks. Each session is composed of 4 elements: a 15 min warm-up that includes strength and balance exercises, a 15 min period with technical pair-based drills, and a 30-min period with small-sided football drills

Primary outcomes

  1. Procollagen type 1 N-terminal propeptide (P1NP)

    Time frame: Baseline and 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 outcomes

  1. Bone resorption markers (CTX and TRAcP)

    Time frame: Baseline, week 2, week 4, week 12 and week 24

    Change in circulating levels of bone resorption markers (C-terminal telopeptide of type 1 collagen (CTX) and Tartrate resistant acid phosphatase (TRAcP))

  2. Bone formation markers (Osteocalcin, bALP, P1NP (other time points))

    Time frame: Baseline, week 2, week 4, week 12 and week 24 (P1NP: week 2, week 4 and week 12)

    Change in circulating levels of bone formation markers (osteocalcin, and bone alkaline phosphatase) and additional time point for P1NP

  3. Bone mineral density (BMD)

    Time frame: Baseline, week 24

    Lumbar spine (L1-4), and total hip and femoral neck bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA)

  4. Bone microarchitecture, mass and geometry

    Time frame: Baseline, week 24

    Bone microarchitecture at the distal radius and tibia assessed using high-resolution peripheral quantitative computed tomography (HR-pQCT)

  5. Muscle fitness and postural balances (test 1)

    Time frame: Baseline, week 24

    Y-balance test

  6. Muscle Fitness and postural balances (test 2)

    Time frame: Baseline, week 24

    Stork balance test

  7. Muscle fitness and postural balances (test 3)

    Time frame: Baseline, week 24

    Handgrip strength test

  8. Muscle fitness and postural balances (test 4)

    Time frame: Baseline, week 24

    leg strength test- knee extension and knee flexion tests

  9. Muscle fitness and postural balances (test 5)

    Time frame: Baseline, 24 weeks

    Sit-to-stand chair test

  10. Muscle fitness and postural balances (test 6)

    Time frame: Baseline, week 24

    stair climb test

  11. Muscle fitness and postural balances (test 7)

    Time frame: Baseline, week24

    Counter Movement Jump test

  12. Cardiopulmonary health (test 1)

    Time frame: Baseline, week 24

    Vo2 max (seismofit)

  13. Cardiopulmonary health (test 2)

    Time frame: Baseline, week 24

    Bicycle test with submaximal exercise (warm-up, submax HR and fat oxidation)

  14. Cardiopulmonary health (test 3)

    Time frame: Baseline, 24 weeks

    5-s peak power test

  15. Cardiopulmonary health (test 4)

    Time frame: Baseline, week 24

    maximal oxygen uptake test

  16. Cardiopulmonary health (test 5)

    Time frame: Baseline, week 24

    6-min walk test

  17. Metabolic health (test 1)

    Time frame: Baseline, week 24

    weight, lean and fat body mass by DXA scanning

  18. Metabolic health (test 2)

    Time frame: Baseline, week 24

    Fasting blood glucose

  19. Metabolic health (test 3)

    Time frame: Baseline, week 24

    Fasting insulin

  20. Metabolic health (test 4)

    Time frame: Baseline, week 24

    Lipid parameters

Other outcomes

  1. SF-12

    Time frame: Baseline, week 24

    Quality of life questionnaire

  2. SASP

    Time frame: Baseline, week 24

    Serum levels of senescence associated secretory phenotype (SASP), which reflect the whole-body burden of senescent cells

Sponsors and collaborators

Lead sponsor

Odense University Hospital

Other

Collaborators

  • Institute of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark.
  • Novo Nordisk A/S
  • OPEN - Odense Patient data Explorative Network, The University of Southern Denmark, Odense, Denmark
  • University of Southern Denmark

Registry information

Official study title

Targeting mTOR With Everolimus and/or Physical Training for Preventing Postmenopausal Bone Loss and Accelerated Skeletal Aging: The RapaLoad Study

Acronym: RapaLoad

Important dates

Study start
2024
Primary completion
2026
Study completion
2026
First posted
Jan 23, 2025
Registry last updated
Apr 7, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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