RANK-ligand Inhibition to Combat Sarcopenia with Underlying Osteoporosis: a Randomized, Double-blind, Double-dummy, Active-Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- 6-metre walk
研究概览
简要总结
The objective of this study was to conduct a randomized, double-blind, double-dummy active controlled trial to determine the efficacy of denosumab in treating sarcopenia with underlying osteoporosis.
详细描述
Aims:
- To assess whether receptor activator of nuclear factor-kB ligand (RANKL)-inhibition can treat sarcopenia in osteosarcopenic patients, in terms of appendicular skeletal muscle mass (ASM), handgrip strength, and physical performance.
- To assess whether RANKL-inhibition improves quality of life, and decreases falls, fractures, hospital admissions and mortality in osteosarcopenic patients.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Elderly males or females aged 65 years or older
- •diagnosed with osteosarcopenia (sarcopenia diagnosis based on AWGS 2019 guidelines - low appendicular skeletal muscle mass (ASM) by Dual-energy X-ray absorptiometry (DXA) (M:<7.0kg/m2, F:<5.4kg/m2) AND low handgrip strength (M:<28kg, F:<18kg) OR low physical performance (6-metre walk: <1.0m/s or 5-time chair stand test ≥ 12 s); osteoporosis diagnosed based on World Health Organization (WHO) criteria with DXA scan T-score ≤ -2.5)
- •Willing and able to comply with study protocol including follow-up evaluations.
排除标准
- •history of recent fracture i.e., within 3 months
- •history of prior anti-osteoporotic drug
- •disease or medication affecting bone or muscle metabolism
- •Chairbound or bedbound
- •Unable to agree for consent
- •contraindication to drug i.e., Denosumab or Zoledronic Acid
- •Underlying malignancy or disease known to cause cachexia
- •severe renal impairment e.g., Creatinine Clearance (CrCl) < 35ml/min
- •moderate to severe liver failure (Child-Pugh Class B or C).
研究组 & 干预措施
Denosumab group
60mg subcutaneous Denosumab (1mL solution) every 6 months and intravenous placebo (100mL normal saline) once yearly
干预措施: Denosumab (Drug)
Zolendronic acid group
5mg intravenous Zoledronic Acid (100mL solution) once yearly and subcutaneous placebo (1mL normal saline) every 6 months
干预措施: Zolendronic Acid (Drug)
结局指标
主要结局
6-metre walk
时间窗: From enrollment to the end of treatment at 52 weeks
The time taken to walk 6 metres without deceleration. Average result of 2 trials is recorded. Slow speed is defined as \&lt;1.0m/s.
5-time chair stand test
时间窗: From enrollment to the end of treatment at 8 weeks
The time to rise from a chair 5 times is recorded. The cut-off for is taken at \&gt;=12 seconds.
Appendicular skeletal muscle mass (ASM)
时间窗: From enrollment to the end of treatment at 52 weeks
Determined with Dual-energy X-ray absorptiometry (Horizon®, DXA system, Hologic, USA). Total ASM by DXA is evaluated by segmented measurement of muscle mass at four limbs by operator-defined cutlines at specific anatomical landmarks. ASM is adjusted to square of height to calculate ASMI (kg/m2). Low ASMI by DXA is \&lt; 7 kg/m2 for men and 5.4 kg/m2 for women.
Handgrip strength
时间窗: From enrollment to the end of treatment at 52 weeks
Assessed by spring-type hand dynamometer (JAMAR Hand Dynamometer 5030JO). Cut-off for men is \&lt; 28kg, and female is \&lt;18kg. Maximum reading of 3 trials using dominant hand in a maximum-effort isometric contraction
Quadriceps muscle strength
时间窗: From enrollment to the end of treatment at 52 weeks
Measured on affected limb with isometric dynamometer (Baseline, Genova, Italy). Subject will sit on a chair with both feet above ground, while raising the affected leg 45° forwards. The dynamometer is placed above the ankle and the subject will push the leg forward with maximum force. Measurements will be repeated 3 times and maximum value will be used for evaluation
Balancing ability
时间窗: From enrollment to the end of treatment at 52 weeks
The Basic Balance Master System (NeuroCom International Inc, USA) is used to measure static and dynamic ability of subjects to maintain center of balance. Subjects will stand barefoot on force plate and control location of their center-of-gravity by weight-shifting to eight different targets. Measured parameters of limits of stability test includes reaction time(s)
次要结局
- Falls(From enrollment to the end of treatment at 52 weeks)
- Fracture(From enrollment to the end of treatment at 52 weeks)
- Quality of life Short Form-36 (SF-36)(From enrollment to the end of treatment at 52 weeks)
- Physical activity scale for elderly (PASE)(From enrollment to the end of treatment at 52 weeks)
- Food frequency questionnaire(From enrollment to the end of treatment at 52 weeks)
- Hospital admissions(From enrollment to the end of treatment at 52 weeks)
- Mortality(From enrollment to the end of treatment at 52 weeks)
研究者
Ronald Man Yeung WONG
Clinical Associate Professor
Prince of Wales Hospital, Shatin, Hong Kong