Sarcopenia in Elderly
Conditions
Brief summary
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.
Detailed description
Aims: 1. 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. 2. To assess whether RANKL-inhibition improves quality of life, and decreases falls, fractures, hospital admissions and mortality in osteosarcopenic patients.
Interventions
DRUGZolendronic Acid
5mg intravenous Zoledronic Acid (100mL solution) once yearly and subcutaneous placebo (1mL normal saline) every 6 months
DRUGDenosumab
60mg subcutaneous Denosumab (1mL solution) every 6 months and intravenous placebo (100mL normal saline) once yearly
Sponsors
Chinese University of Hong Kong
Prince of Wales Hospital, Shatin, Hong Kong
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 6-metre walk | 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 <1.0m/s. |
| 5-time chair stand test | 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 >=12 seconds. |
| Appendicular skeletal muscle mass (ASM) | 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 < 7 kg/m2 for men and 5.4 kg/m2 for women. |
| Handgrip strength | 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 < 28kg, and female is <18kg. Maximum reading of 3 trials using dominant hand in a maximum-effort isometric contraction |
| Quadriceps muscle strength | 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 | 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 directional control (%). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Falls | From enrollment to the end of treatment at 52 weeks | To assess the occurrence of falls, patients are required to self-report via a fall calendar, which will be returned at 1-year |
| Mortality | From enrollment to the end of treatment at 52 weeks | Mortality within 1-year of study period is documented. |
| Fracture | From enrollment to the end of treatment at 52 weeks | Assess occurrence of a fracture within a year of study period. |
| Quality of life Short Form-36 (SF-36) | From enrollment to the end of treatment at 52 weeks | The highest score is 900, and the lowest score is 0. Highest score indicates a better quality of life. |
| Physical activity scale for elderly (PASE) | From enrollment to the end of treatment at 52 weeks | It assesses the types of activities typically chosen by older adults, ranging from 0 to 793, with higher scores indicating greater physical activity |
| Food frequency questionnaire | From enrollment to the end of treatment at 52 weeks | Daily and weekly intake of 280 food items will be performed using a validated food frequency questionnaire developed in a local population survey. Mean nutrient quantitation and energy intake per day will be calculated referring to food composition tables derived from the Chinese Medical Sciences Institute and Centre for Food Safety in Hong Kong. |
| Hospital admissions | From enrollment to the end of treatment at 52 weeks | Number and cause of emergency hospital admission within 1 year of study period are documented. |
Countries
China
Contacts
Primary ContactRonald Man Yeung Wong
Outcome results
None listed