RANKL Inhibition to Combat Sarcopenia in Hip Fracture Patients

Condition(s) studied

Investigational drug(s) / intervention(s)

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

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

Study 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.

Eligibility

Primary outcome measure(s)

• Sarcopenia and Quality of Life (SarQoL®) — From enrolment to 24 months after the start of treatment
  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.
• Quadriceps muscle strength — From enrolment to 24 months after the start of treatment
  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
• Handgrip strength — From enrolment to 24 months after the start of treatment
  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
• Appendicular skeletal muscle mass (ASM) — From enrolment to 24 months after the start of treatment
  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.
• 5-time chair stand test — From enrolment to 24 months after the start of treatment
  The time to rise from a chair 5 times is recorded. Low physical performance is ≥ 12 seconds.
• 6-metre walk — From enrolment to 24 months after the start of treatment
  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
• Short Physical Performance Battery — From enrolment to 24 months after the start of treatment
  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.
• Balancing ability — From enrolment to 24 months after the start of treatment
  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).
• Balancing ability — From enrolment to 24 months after the start of treatment
  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 (%).
• Balancing ability — From enrolment to 24 months after the start of treatment
  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).
• Balancing ability — From enrolment to 24 months after the start of treatment
  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 (%).
• Balancing ability — From enrolment to 24 months after the start of treatment
  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 (%).

Trial sites (1)

More Prince of Wales Hospital, Shatin, Hong Kong trials in China

Other trials for the same condition