Targeting mTOR with everolimus and/or physical training for preventing postmenopausal bone loss and accelerated skeletal aging. The RapaLoad study.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Odense University Hospital

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Hormonal diseases [C19]

Trial duration

20 Oct 2024 → ongoing

Decision date (initial)

2024-08-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

NovoNordisk Foundation

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

This study aims to determine if treatment with everolimus, exercise training, or their combination for 24 weeks enhances bone formation in healthy postmenopausal women.

Conditions and MedDRA coding

Healthy

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. - 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.
2. - No history of low energy hip or vertebral fractures during the last 6 months.
3. Ability to provide informed consent.

Exclusion criteria 18

1. - Diabetes (type 1 and 2)
2. Heart failure similar to NYHA Class IV
3. Primary hyperparathyroidism
4. Known disorders affecting bone metabolism, e.g., uncontrolled thyrotoxicosis, severe renal im-pairment (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
5. Previous use of bone antiresorptive or bone anabolic drugs within the last 5 years
6. Use of anabolic steroids in the previous year
7. Treatment with drugs known to affect cytochrome P450 3A due to its role in everolimus metab-olism
8. History of coagulopathy or medical condition requiring long-term anticoagulation
9. Anemia – Hg < 9.0 g/dl, Leukopenia – white blood cells (WBC) < 3,500/mm3, Neutropenia abso-lute neutrophil count < 2,000/mm3, or Platelet count – platelet count < 125,000/mm3
10. Patients with impaired wound healing or history of a chronic open wound
11. Scheduled for immunosuppressant therapy for transplant or scheduled to undergo chemother-apy or any other treatment for malignancy
12. Untreated dyslipidemia with LDL-c > 4.9 mmol/L and family history of dyslipidemia, Total cho-lesterol > 9.1 mmol/L, or triglycerides > 9.9 mmol/L
13. Any form of clinically relevant primary or secondary immune dysfunction or deficiency
14. Unstable ischemic heart disease
15. Bone mineral density (BMD) measured by DXA scanning with T-score <-3
16. Known allergy to rapamycin or rapalogs
17. The study will exclude participants with inability to speak and understand Danish and with ina-bility to cooperate or perform physical training
18. Inability to give informed consent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. - 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 endpoints 6

1. - Change in circulating levels of bone turnover markers: 1)Bone resorption markers (C-terminal telopeptide of type 1 collagen (CTX) and Tartrate resistant acid phosphatase (TRAcP)) at baseline, 4, 12 and 24 weeks. 2) Bone formation markers (osteocalcin, and bone alkaline phosphatase) at baseline, 4, 12 and 24 weeks and P1NP at 4 and 12weeks
2. - Lumbar spine (L1-4), and total hip and femoral neck bone mineral density (BMD) meas-ured by dual-energy X-ray absorptiometry (DXA) at baseline and 24 weeks
3. - Bone microarchitecture, mass, and geometry at the distal radius and tibia assessed us-ing high-resolution peripheral quantitative computed tomography (HR-pQCT) at base-line and 24 weeks
4. - Muscle function and postural balances tested at base-line and 24 weeks
5. - Cardiopulmonary health estimated by measuring Vo2max at baseline and week 24.
6. - Metabolic health: weight, body composition by DXA scanning, fasting blood glucose, fasting insulin, lipid parameters and metabolomic studies at baseline and week 24.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Odense University Hospital

Sponsor organisation

Odense University Hospital

Address

J B Winsloews Vej 4

City

Odense C

Postcode

5000

Country

Denmark

Scientific contact point

Organisation

Odense University Hospital

Contact name

Florence Figeac

Public contact point

Organisation

Odense University Hospital

Contact name

Florence Figeac

Third parties 2

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

3 submissions — initial application plus substantial / non-substantial modifications