EVEROLIMUS for Postmenopausal bone loss|Accelerated skeletal aging

Inclusion criteria

• {"criterion_text":"- 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.\n- No history of low energy hip or vertebral fractures during the last 6 months.\n- Ability to provide informed consent."}

Exclusion criteria

• {"criterion_text":"- Diabetes (type 1 and 2)\n- Patients with impaired wound healing or history of a chronic open wound\n- Scheduled for immunosuppressant therapy for transplant or scheduled to undergo chemother-apy or any other treatment for malignancy\n- 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\n- Any form of clinically relevant primary or secondary immune dysfunction or deficiency\n- Unstable ischemic heart disease\n- Bone mineral density (BMD) measured by DXA scanning with T-score <-3\n- Known allergy to rapamycin or rapalogs\n- The study will exclude participants with inability to speak and understand Danish and with ina-bility to cooperate or perform physical training\n- Inability to give informed consent\n- Heart failure similar to NYHA Class IV\n- Primary hyperparathyroidism\n- 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\n- Previous use of bone antiresorptive or bone anabolic drugs within the last 5 years\n- Use of anabolic steroids in the previous year\n- Treatment with drugs known to affect cytochrome P450 3A due to its role in everolimus metab-olism\n- History of coagulopathy or medical condition requiring long-term anticoagulation\n- 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"}

Primary endpoints

• {"endpoint_text":"-\tPercentage change in circulating levels of bone formation marker N-terminal fragment of procollagen type 1 (P1NP) at 24 weeks as compared with baseline.","definition_or_measurement_approach":"Percentage change in circulating levels of P1NP measured at 24 weeks compared with baseline."}

Secondary endpoints

• {"endpoint_text":"-\tChange 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)\tBone formation markers (osteocalcin, and bone alkaline phosphatase) at baseline, 4, 12 and 24 weeks and P1NP at 4 and 12weeks","definition_or_measurement_approach":"Measurement of specified bone resorption and bone formation markers at baseline, weeks 4, 12 and 24 (P1NP additionally at weeks 4 and 12)."}
• {"endpoint_text":"-\tLumbar 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","definition_or_measurement_approach":"BMD assessed by DXA at lumbar spine (L1-4), total hip, and femoral neck at baseline and week 24."}
• {"endpoint_text":"-\tBone 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","definition_or_measurement_approach":"HR-pQCT assessment of bone microarchitecture, mass, and geometry at distal radius and tibia at baseline and week 24."}
• {"endpoint_text":"-\tMuscle function and postural balances tested at base-line and 24 weeks","definition_or_measurement_approach":"Muscle function and postural balance tests performed at baseline and week 24."}
• {"endpoint_text":"-\tCardiopulmonary health estimated by measuring Vo2max at baseline and week 24.","definition_or_measurement_approach":"VO2max measurement at baseline and week 24 to estimate cardiopulmonary health."}
• {"endpoint_text":"-\tMetabolic health: weight, body composition by DXA scanning, fasting blood glucose, fasting insulin, lipid parameters and metabolomic studies at baseline and week 24.","definition_or_measurement_approach":"Assessments of weight, DXA body composition, fasting glucose, fasting insulin, lipid panel, and metabolomics at baseline and week 24."}

Denmark

Earliest CTIS Part Ii Submission Date

02-08-2024

Latest Decision Or Authorization Date

09-08-2024

Processing Time Days

7

Number Of Sites

1

Number Of Participants

136

Primary sponsor

Full Name

Odense University Hospital

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Denmark

Third parties

• {"country":"Denmark","full_name":"Odense University Hospital","duties_or_roles":"codes: 1,7,8; contact email: open@rsyd.dk","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Denmark","full_name":"Institut for idræt og biomekanik","duties_or_roles":"codes: 15 (DXA-scans, blood sampling, general health fitness test), 2; contact email: pkrustrup@health.sdu.dk","organisation_type":"Educational Institution"}