RANKL Inhibition to Combat Sarcopenia in Hip Fracture Patients

Prince of Wales Hospital

Status and phase: Begins enrollment in 4 months; Phase 3

Conditions: Sarcopenia in Elderly

Treatments: Drug: Zoledronic acide (Aclasta); Drug: Denosumab (Prolia)

Study type: Interventional

Funder types: Other

Identifiers

NCT07056478

2023.401

Details and patient eligibility

About

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.

Full 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.

Enrollment: 130 estimated patients

Sex: All

Ages: 65+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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130 participants in 2 patient groups, including a placebo group

Denosumab group

Active Comparator group

Description:

60mg subcutaneous Denosumab (1mL solution) every 6 months and intravenous placebo (100mL normal saline) once yearly

Treatment:

Drug: Denosumab (Prolia)

Zolendronic acid group

Placebo Comparator group

Description:

5mg intravenous Zoledronic Acid (100mL solution) once yearly and subcutaneous placebo (1mL normal saline) every 6 months

Treatment:

Drug: Zoledronic acide (Aclasta)