Resistance Training and Rapamycin to Enhance Bone Formation in Postmenopausal Women
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 148
- 试验地点
- 4
- 主要终点
- P1NP
研究概览
简要总结
The aim of the present clinical trial is to examine the effects of everolimus, resistance training, or their combination on bone and muscle health formation in elderly women aged 60-75 years. The main questions it aims to answer are:
Can rapamycin's analog (Everolimus), resistance training, or their combination, enhance bone formation and muscle functions in elderly women compared to non-treatment controls.
Participants will be randomized 1:1:1:1 to one of the following treatment regimens:
- Oral everolimus 5 mg once a week.
- Oral placebo once a week.
- Oral everolimus 5 mg once a week plus resistance training RT 1 hour, 3 times weekly.
- Oral placebo once a week plus resistance training RT 1 hour, 3 times weekly.
During the study there will be a total of 5-7 visits, where the participants will undergo the following:
- Blood samles
- DXA-, HRpQCT- (only Odense Universitetshospital) and MRI-scans
- Muscle- and bone biopsies
- Quality of life questionnaires
- Testing of muscle funtion
- Metabolic studies of muscle and bone protein turnover using labelling with deuturated water
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Treatment allocation to rapamycin or placebo is double-blinded, while allocation to training or no training will be known to participants and investigators, but masked to the statistician.
入排标准
- 年龄范围
- 60 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Women aged 60-75 years old, any ethnicity.
- •Participants with T- score between < 1.0 and > -2.5 measured by DXA scan within 6 months of the first day of the study.
- •Adequate cognitive function to be able to give informed consent.
排除标准
- •Osteoporosis and fracture history
- •Participants with osteoporosis (defined by DXA scan < 6 months old: low bone mass, T-score < -2.5 or hip fracture or clinical compression fracture of the spine).
- •History of low energy fractures within last 6 months. Health conditions limiting exercise
- •Health conditions that could limit walking and weightbearing exercise (for instance recent surgery, mobility limitation)
- •Participants with impaired wound healing or history of a chronic open wound Bone metabolism disorders
- •Primary hyperparathyroidism.
- •Known vitamin D deficiency (<25 nM) (re-test after substitution acceptable).
- •Known disorders affecting bone metabolism, e.g., uncontrolled thyrotoxicosis, severe renal impairment (eGFR < 30) or impaired 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.
- •Medication use and health conditions
- •Use of anabolic steroids in the previous year.
- •Use of antiresorptive therapy in the previous year.
- •Known medication/supplements affecting bone in the previous year.
- •Diabetes type 1 and
- •Heart failure similar to NYHA Class IV.
- •Treatment with drugs known to affect cytochrome P450 3A due to its role in everolimus metabolism, excluding strong CYP3A4 inhibitors or inducers, while allowing weak and intermediate inhibitors or inducers. Patients on the following drugs will be excluded from the trial: Ketoconazole, Itraconazole, Posaconazole, Voriconazole, Telithromycin, Clarithromycin, Nedazodone, Ritonavir, Atazanavir, Saquinavir, Darunavir, Indinavir, Nelfinavir, Rifampicin, Dexamethasone, Carbamazepine, phenobarbital, Phenytoin, Efavirenz and Nivirapine.
- •History of coagulopathy or medical condition requiring long-term anticoagulation.
- •Blood disorders and other health concerns
- •Anemia - Hg < 5,59 mmol/L, Leukopenia - white blood cells (WBC) < 3,5 x 10⁹/L, Neutropenia absolute neutrophil count < 2,0 x 10⁹/L, or Platelet count - platelet count < 125 x 10⁹/L.
- •Insufficiently treated 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.
- •Immunosuppressive and current cancer Treatment
- •Scheduled for immunosuppressant therapy for transplant or scheduled to undergo chemotherapy or any other treatment for malignancy
- •Any form of clinically relevant primary or secondary immune dysfunction or deficiency Cardiovascular and heart conditions
- •Unstable ischemic heart disease.
- •Known allergy to rapamycin or rapalogs. Language limitations
- •The study will exclude participants with inability to speak and understand Danish and with inability to cooperate.
研究组 & 干预措施
Everolimus and resistance training
Oral everolimus 5 mg once a week plus resistance training RT 1 hour, 3 times weekly
干预措施: Resistance training (Other)
Placebo
Oral placebo once a week
干预措施: Placebo (Drug)
Placebo and resistance training
Oral placebo once a week plus resistance training RT 1 hour, 3 times weekly
干预措施: Placebo (Drug)
Placebo and resistance training
Oral placebo once a week plus resistance training RT 1 hour, 3 times weekly
干预措施: Resistance training (Other)
Everolimus
Oral everolimus 5 mg once a week
干预措施: Everolimus (Drug)
Everolimus and resistance training
Oral everolimus 5 mg once a week plus resistance training RT 1 hour, 3 times weekly
干预措施: Everolimus (Drug)
结局指标
主要结局
P1NP
时间窗: From baseline to end of treatment at 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
次要结局
- Bone resorption markers(From baseline to end of treatment 24 weeks)
- BMD(From screening to end of treatment 24 weeks)
- Bone mass(From baseline to end of treatment 24 weeks)
- Bone microarchitecture(From baseline to end of treatment 24 weeks)
- Bone geometry(From baseline to end of treatment (24 weeks))
- Muscle Cross-Sectional Area(From baseline to end of treatment 24 weeks)
- Muscle assessment(From baseline to end of treatment 24 weeks)
- Metabolic health (test 1)(From baseline to end of treatment 24 weeks)
- Quality of life quiestionaire(From baseline to end of treatment 24 weeks)
- Muscle function (power)(From baseline to end of treatment 24 weeks.)
- Bone formation markers(From baseline to end of study 24 weeks)
- Metabolic health (test 2)(From screening to end of treatment 24 weeks)
- Metabolic health (test 3)(From baseline to end of treatment 24 weeks)
- Metabolic Health (Test 4)(From screening to end treatment)
- Metabolic health (test 5)(From screening to end of treatment 24 weeks)