RANK-ligand Inhibition to Combat Sarcopenia with Underlying Osteoporosis

Prince of Wales Hospital

Status and phase: Enrolling; Phase 4

Conditions: Sarcopenia in Elderly

Treatments: Drug: Zolendronic Acid; Drug: Denosumab

Study type: Interventional

Funder types: Other

Identifiers

NCT06643780

2022.555

Details and patient eligibility

About

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.

Full 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.

Enrollment: 120 estimated patients

Sex: All

Ages: 65+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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120 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

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: Zolendronic Acid