RANK-ligand Inhibition to Combat Sarcopenia with Underlying Osteoporosis

NCT06643780 | Recruiting Phase 4

• 1 other identifier: 2022.555
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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.

Conditions

Sarcopenia in Elderly

Outcome Measures

Primary Outcomes (10)

• 6-metre walk

  The time taken to walk 6 metres without deceleration. Average result of 2 trials is recorded. Slow speed is defined as \<1.0m/s.

  From enrollment to the end of treatment at 52 weeks

• 5-time chair stand test

  The time to rise from a chair 5 times is recorded. The cut-off for is taken at \>=12 seconds.

  From enrollment to the end of treatment at 8 weeks

• Appendicular skeletal muscle mass (ASM)

  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.

  From enrollment to the end of treatment at 52 weeks

• Handgrip strength

  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

  From enrollment to the end of treatment at 52 weeks

• 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 the subject will push the leg forward with maximum force. Measurements will be repeated 3 times and maximum value will be used for evaluation

  From enrollment to the end of treatment at 52 weeks

• 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 enrollment to the end of treatment at 52 weeks

• 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 enrollment to the end of treatment at 52 weeks

• 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 enrollment to the end of treatment at 52 weeks

• 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 enrollment to the end of treatment at 52 weeks

• 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 enrollment to the end of treatment at 52 weeks

Secondary Outcomes (7)

• Falls

  From enrollment to the end of treatment at 52 weeks

• Fracture

  From enrollment to the end of treatment at 52 weeks

• Quality of life Short Form-36 (SF-36)

  From enrollment to the end of treatment at 52 weeks

• Physical activity scale for elderly (PASE)

  From enrollment to the end of treatment at 52 weeks

• Food frequency questionnaire

  From enrollment to the end of treatment at 52 weeks

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

Zolendronic acid group

PLACEBO COMPARATOR

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

Drug: Zolendronic Acid

Interventions

Denosumab DRUG

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

Denosumab group

Zolendronic Acid 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 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Prince of Wales Hospital, Shatin, Hong Kong: lead
• Chinese University of Hong Kong: collaborator

Study Sites (1)

The Chinese University of Hong Kong

Hong Kong, China

RECRUITING

Related Publications (1)

• Wong RMY, Wong PY, Liu C, Tang N, Wan RCW, Liu WH, Cui C, Zhang N, Kwok TCY, Law SW, Cheung WH. RANK-ligand inhibition to combat sarcopenia with underlying osteoporosis: a study protocol for a randomized, double-blind, double-dummy, active-controlled trial. Trials. 2025 Aug 4;26(1):269. doi: 10.1186/s13063-025-08976-7.

  PMID: 40760465 DERIVED

MeSH Terms

Interventions

Denosumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Ronald Man Yeung Wong

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 4
• 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: September 15, 2024
• First Posted: October 16, 2024
• Study Start: April 9, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: October 16, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)