RANK-ligand Inhibition to Combat Sarcopenia with Underlying Osteoporosis

Phase 4
Recruiting
Conditions
Interventions
Registration Number
NCT06643780
Lead Sponsor
Prince of Wales Hospital, Shatin, Hong Kong
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.

Detailed 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.
...

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
120
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.
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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).
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Denosumab groupDenosumab60mg subcutaneous Denosumab (1mL solution) every 6 months and intravenous placebo (100mL normal saline) once yearly
Zolendronic acid groupZolendronic Acid5mg intravenous Zoledronic Acid (100mL solution) once yearly and subcutaneous placebo (1mL normal saline) every 6 months
Primary Outcome Measures
NameTimeMethod
6-metre walkFrom enrollment to the end of treatment at 52 weeks

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

5-time chair stand testFrom enrollment to the end of treatment at 8 weeks

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

Appendicular skeletal muscle mass (ASM)From enrollment to the end of treatment at 52 weeks

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 ...

Handgrip strengthFrom enrollment to the end of treatment at 52 weeks

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

Quadriceps muscle strengthFrom enrollment to the end of treatment at 52 weeks

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 e...

Balancing abilityFrom enrollment to the end of treatment at 52 weeks

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 ...

Secondary Outcome Measures
NameTimeMethod
FallsFrom enrollment to the end of treatment at 52 weeks

To assess the occurrence of falls, patients are required to self-report via a fall calendar, which will be returned at 1-year

FractureFrom enrollment to the end of treatment at 52 weeks

Assess occurrence of a fracture within a year of study period.

Quality of life Short Form-36 (SF-36)From enrollment to the end of treatment at 52 weeks

The highest score is 900, and the lowest score is 0. Highest score indicates a better quality of life.

Physical activity scale for elderly (PASE)From enrollment to the end of treatment at 52 weeks

It assesses the types of activities typically chosen by older adults, ranging from 0 to 793, with higher scores indicating greater physical activity

Food frequency questionnaireFrom enrollment to the end of treatment at 52 weeks

Daily and weekly intake of 280 food items will be performed using a validated food frequency questionnaire developed in a local population survey. Mean nutrient quantitation and energy intake per day will be calculated referring to food composition tables derived from the Chinese Medical Sciences Institute and Centre for Food Safety in Hong Kong.

Hospital admissionsFrom enrollment to the end of treatment at 52 weeks

Number and cause of emergency hospital admission within 1 year of study period are documented.

MortalityFrom enrollment to the end of treatment at 52 weeks

Mortality within 1-year of study period is documented.

Trial Locations

Locations (1)

The Chinese University of Hong Kong

🇨🇳

Hong Kong, China

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