RANKL Inhibition to Combat Sarcopenia in Hip Fracture Patients

NCT07056478 | Not Yet Recruiting Phase 3

• 1 other identifier: 2023.401
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

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.

Conditions

Sarcopenia in Elderly

Outcome Measures

Primary Outcomes (12)

• Sarcopenia and Quality of Life (SarQoL®)

  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.

  From enrolment to 24 months after the start of treatment

• Quadriceps muscle strength

  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

  From enrolment to 24 months after the start of treatment

• Handgrip strength

  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

  From enrolment to 24 months after the start of treatment

• Appendicular skeletal muscle mass (ASM)

  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.

  From enrolment to 24 months after the start of treatment

• 5-time chair stand test

  The time to rise from a chair 5 times is recorded. Low physical performance is ≥ 12 seconds.

  From enrolment to 24 months after the start of treatment

• 6-metre walk

  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

  From enrolment to 24 months after the start of treatment

• Short Physical Performance Battery

  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.

  From enrolment to 24 months after the start of treatment

• Balancing ability

  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).

  From enrolment to 24 months after the start of treatment

• Balancing ability

  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 (%).

  From enrolment to 24 months after the start of treatment

• Balancing ability

  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 movement velocity (degrees/s).

  From enrolment to 24 months after the start of treatment

• Balancing ability

  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 endpoint excursion (%).

  From enrolment to 24 months after the start of treatment

• Balancing ability

  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 maximum excursion (%).

  From enrolment to 24 months after the start of treatment

Secondary Outcomes (5)

• Falls

  From enrolment to 24 months after the start of treatment

• Hospital re-admissions

  From enrolment to 24 months after start of treatment

• Secondary fracture

  From enrolment to 24 months after start of treatment

• Mortality

  From enrolment to 24 months after start of treatment

• Bone mineral density (BMD)

  From enrolment to 24 months after the start of treatment

Study Arms (2)

Denosumab group

ACTIVE COMPARATOR

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

Drug: Denosumab (Prolia)

Zolendronic acid group

PLACEBO COMPARATOR

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

Drug: Zoledronic acide (Aclasta)

Interventions

Denosumab (Prolia) DRUG

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

Denosumab group

Zoledronic acide (Aclasta) DRUG

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

Zolendronic acid group

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Prince of Wales Hospital, Shatin, Hong Kong: lead

Study Sites (1)

The Chinese University of Hong Kong

Hong Kong, China

Location

MeSH Terms

Interventions

Denosumab; Zoledronic Acid

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Ronald Man Yeung Wong

CONTACT

852 3505 1654; ronald.wong@cuhk.edu.hk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Associate Professor

Study Record Dates

• First Submitted: June 19, 2025
• First Posted: July 9, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2030
• Last Updated: July 9, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)