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

NCT06789900 | Recruiting Phase 2 DMC

• 1 other identifier: EU CT: 2023-508093-28-00
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 2

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. 1.control group getting general health advice,
2. 2.Football fitness session group, physical training consisting of structured hybrid exercise training via the "football fitness concept" for 1hour, 2 times/ week
3. 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.

Conditions

Postmenopausal Women

Keywords

Everolimus; Exercise; Football training session; postmenopausal women; bone loss; skeletal aging

Outcome Measures

Primary Outcomes (1)

• Procollagen type 1 N-terminal propeptide (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

  Baseline and 24 weeks

Secondary Outcomes (20)

• Bone resorption markers (CTX and TRAcP)

  Baseline, week 2, week 4, week 12 and week 24

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

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

• Bone mineral density (BMD)

  Baseline, week 24

• Bone microarchitecture, mass and geometry

  Baseline, week 24

• Muscle fitness and postural balances (test 1)

  Baseline, week 24

Other Outcomes (2)

• SF-12

  Baseline, week 24

• SASP

  Baseline, week 24

Study Arms (4)

Control group

NO INTERVENTION

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

Football fitness group

EXPERIMENTAL

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.

Other: Football Fitness Concept

Everolimus group

EXPERIMENTAL

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

Drug: Everolimus (Afinitor®)

Everolimus and Football fitness group

EXPERIMENTAL

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.

Drug: Everolimus (Afinitor®); Other: Football Fitness Concept

Interventions

Everolimus (Afinitor®) DRUG

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

Also known as: Football fitness session

Everolimus and Football fitness group; Everolimus group

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

Everolimus and Football fitness group; Football fitness group

Eligibility Criteria

• Age: 45 Years - 60 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (2)

Odense University Hospital

Odense, 5000, Denmark

NOT YET RECRUITING

Odense University Hospital

Odense, 5000, Denmark

RECRUITING

MeSH Terms

Conditions

Motor Activity; Bone Diseases, Metabolic

Interventions

Everolimus

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Moustapha Kassem, DMSc, PhD

  Odense University Hospital

  PRINCIPAL INVESTIGATOR

• Florence Figeac, PhD

  Odense University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sofie Damkjær, MD

CONTACT

+4520575198; sofie.damkjaer.hansen@rsyd.dk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2024
• First Posted: January 23, 2025
• Study Start: October 14, 2024
• Primary Completion: July 1, 2025
• Study Completion: July 1, 2025
• Last Updated: January 23, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

DK (2)