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

NCT ID: NCT06789900

Last Updated: 2025-01-23

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 136 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-10-14
• Study Completion Date: 2025-07-31

Brief Summary

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.

Conditions

Postmenopausal Women

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Control group

Participants will be asked to continue their life as usual with no specific recommendation

Group Type: NO_INTERVENTION

No interventions assigned to this group

Football fitness group

Participants will join structured hybrid exercise training via the "football fitness concept" 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: 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.

Group Type: EXPERIMENTAL

Football Fitness Concept

Intervention Type: 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

Everolimus group

Participants will take an oral dose of everolimus 5 mg once a week for 24 weeks.

Group Type: EXPERIMENTAL

Everolimus (Afinitor®)

Intervention Type: DRUG

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

Everolimus and Football fitness group

Participants will join structured hybrid exercise training via the "football fitness concept" 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: 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 and take an oral dose of everolimus 5 mg once a week for 24 weeks.

Group Type: EXPERIMENTAL

Everolimus (Afinitor®)

Intervention Type: DRUG

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

Football Fitness Concept

Intervention Type: 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

Interventions

Everolimus (Afinitor®)

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

Intervention Type: DRUG

Football Fitness Concept

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

Intervention Type: OTHER

Other Intervention Names

Football fitness session

Eligibility Criteria

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

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Institute of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark.

UNKNOWN

Sponsor Role: collaborator

OPEN - Odense Patient data Explorative Network, The University of Southern Denmark, Odense, Denmark

UNKNOWN

Sponsor Role: collaborator

Novo Nordisk A/S

INDUSTRY

Sponsor Role: collaborator

Odense University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Moustapha Kassem, DMSc, PhD

Role: PRINCIPAL_INVESTIGATOR

Odense University Hospital

Florence Figeac, PhD

Role: PRINCIPAL_INVESTIGATOR

Odense University Hospital

Locations

Odense University Hospital

Odense, , Denmark

Site Status: NOT_YET_RECRUITING

Odense University Hospital

Odense, , Denmark

Site Status: RECRUITING

Countries

Denmark

Central Contacts

Sofie Damkjær, MD

Role: CONTACT

sofie.damkjaer.hansen@rsyd.dk

+4520575198

Facility Contacts

Sofie Damkjær, MD

Role: primary

sofie.damkjaer.hansen@rsyd.dk

+4520575198

Other Identifiers

EU CT: 2023-508093-28-00

Identifier Type: -

Identifier Source: org_study_id