Sarcopenia in Elderly
Conditions
Brief summary
The objective of this study is to conduct a pragmatic, randomized, double-blind, active-controlled trial to assess the efficacy of receptor activator of nuclear factor-kB ligand (RANKL) inhibition in the treatment of sarcopenia in hip fractures.
Detailed description
Objectives 1. To investigate the effect of RANKL inhibition in treating sarcopenia in hip fracture patients in terms of physical performance and quality of life. 2. To investigate the effect of RANKL inhibition in treating sarcopenia in hip fracture patients in terms of appendicular skeletal muscle mass and muscle strength. 3. To investigate the efficacy of RANKL inhibition in treating sarcopenia in hip fracture patients in terms of falls, hospital re-admissions, re-fractures, and mortality.
Interventions
60mg subcutaneous Denosumab (1mL solution) every 6 months and intravenous placebo (100mL normal saline) once yearly
DRUGZoledronic acide (Aclasta)
5mg intravenous Zoledronic Acid (100mL solution) once yearly and subcutaneous placebo (1mL normal saline) every 6 months
Sponsors
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 aged 65 years or older * Diagnosed with sarcopenia following AWGS guidelines - low appendicular skeletal muscle mass measured by dual-energy x-ray absorptiometry (Cutoff: Male \<7.0kg/m2, and female \<5.4kg/m2) AND low handgrip strength (Cutoff: Male \< 28kg, Female \<18 kg) OR low physical performance (6-metre walk, cutoff: \<1.0m/s or 5-time chair stand test \>=12s) * Diagnosed with a hip fracture from low-energy mechanism (e.g., falling from standing height) requiring an operation * Willing and able to comply with study protocol including follow-up evaluations.
Exclusion criteria
* open fracture * multiple fractures * pathological fractures e.g., tumour, infection, etc. * history of medication or disease affecting bone metabolism e.g., hypo/hyperthyroidism * malignancy * chairbound or bedbound (unable to perform assessments) * serious cognitive problems e.g., severe dementia (unable to agree for consent) - renal impairment with glomerular filtration rate \<30 mL/min * prior anti-osteoporotic medication e.g. bisphosphonates, denosumab, etc. * active infection, * severe malnutrition i.e. Mini Nutritional Assessment \< 17 points * serious neurological or neuromuscular conditions e.g. Parkinson's disease * uncontrolled chronic conditions e.g. poorly controlled diabetes mellitis * not anaesthetically fit for operation or conservative management
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sarcopenia and Quality of Life (SarQoL®) | From enrolment to 24 months after the start of treatment | Health-related questionnaire for sarcopenia which is composed of 55 items translated into 22 questions and organized into seven domains of quality of life including physical and mental health, locomotion, body composition, functionality, activities of daily living, leisure activities, and fears. The SarQoL involves an overall score, which is the sum of seven individual domain scores, with higher scores indicating better quality of life. During the scoring process, the overall and domain scores are rescaled such that their maximum possible values become 100. |
| Quadriceps muscle strength | From enrolment to 24 months after the start of treatment | 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 subject will push the leg forward with maximum force. Measurements are repeated three times and maximum value used for evaluation |
| Handgrip strength | From enrolment to 24 months after the start of treatment | Assessed by handgrip strength with spring-type hand dynamometer (JAMAR Hand Dynamometer 5030JO; Sammons Preston, Bolingbrook, IL). The maximum reading of 2 trials using the dominant hand in a maximum-effort isometric contraction is taken. Male \< 28kg, and female \<18kg are cut-off for low handgrip strength |
| Appendicular skeletal muscle mass (ASM) | From enrolment to 24 months after the start of treatment | Determined with Dual-energy X-ray absorptiometry (Horizon®, Hologic, USA). Total appendicular skeletal mass (ASM) 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 appendicular skeletal mass index (ASMI) (kg/m2). Cutoff of low ASMI is defined as Male \<7.0kg/m2, and female \<5.4kg/m2. |
| 5-time chair stand test | From enrolment to 24 months after the start of treatment | The time to rise from a chair 5 times is recorded. Low physical performance is ≥ 12 seconds. |
| 6-metre walk | From enrolment to 24 months after the start of treatment | The time taken to walk 6 metres without deceleration is taken. The average result of 2 trials is taken and recorded. Low physical performance is \<1.0m/s |
| Short Physical Performance Battery | From enrolment to 24 months after the start of treatment | Performed by balance test (side-by-side stand, semi-tandem stand, and tandem stand), gait speed test (time for 4-meter walk), and chair stand test (5 repeats). Low physical performance is ≤ 9. |
| Balancing ability | From enrolment to 24 months after the start of treatment | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Falls | From enrolment to 24 months after the start of treatment | Patients self-report via fall calendar, which will be returned at each follow-up. Calendar reporting has been well proven to be reliable for fall studies |
| Hospital re-admissions | From enrolment to 24 months after start of treatment | Documented from Clinical Management System (CMS) from Hospital Authority (public computerized system for all patients) |
| Secondary fracture | From enrolment to 24 months after start of treatment | Confirmed via X-ray/radiology report and Clinical Management System (CMS). Lateral X-ray of spine also taken during follow-up to detect the often clinically silent vertebral fracture. Vertebra is assessed by Genant classification as per our previously established protocol |
| Mortality | From enrolment to 24 months after start of treatment | Documented from the Clinical Management System (CMS) from Hospital Authority (public computerized system for all patients) |
| Bone mineral density (BMD) | From enrolment to 24 months after the start of treatment | Measured by Dual-energy X-ray absorptiometry (Horizon®, Hologic, US) at lumbar spine and contralateral hip |
Countries
China
Contacts
CONTACTRonald Man Yeung Wong
Outcome results
None listed