RCT of Combination Effect of Vibration Treatment and HMB Supplementation on Myosteatosis and NMJ Degeneration

Dissecting the Therapeutic Mechanism of an Effective Combination Treatment Targeting Neuromuscular Junction Dengeneration and Myosteatosis to Combat Sarcopenia

The investigators' pre-clinical study confirms the positive effects of combined treatment (VT + HMB) on reducing fat-to-lean tissue ratio, intramuscular fat infiltration and increasing muscle strength in sarcopenia animal model. The results showed that fat mass could be decreased by ~32%, while histology Oil Red O staining indicated a decrease of fat by almost 60%; in contrast, lean muscle mass increased by ~14%. On muscle strength, combined treatment increased twitch force, tetanic force and grip strength by ~30-66%. These in vivo results are very encouraging and the investigators should explore its potential in clinical translation. As VT and HMB supplement have been commercially available and their compliance rates are satisfactory, they can be translated to clinical application easily. The investigators' next step is to confirm its clinical efficacy, so that sarcopenia becomes a new indication of VT and HMB. The hypothesis is that combined treatment of VT and HMB can retard the progression of sarcopenia in human, in terms of muscle mass, muscle strength and performance.

Study Overview

• Status: Recruiting
• Conditions: Sarcopenia; Musculoskeletal Abnormalities; Connective Tissue Diseases in Old Age
• Intervention / Treatment: Dietary supplement: Protein supplement; Dietary supplement: β-hydroxy β-methylbutyrate (HMB) supplement; Device: Low-magnitude High-frequency Vibration

Detailed Description

In this study, a single-blinded RCT is to investigate the effect of combination treatment of VT and HMB on hand grip, gait speed, muscle mass (DXA) in sarcopenic subjects.

Subjects over age of 65 will be screened by performing SARC-F, handgrip, gait speed and bioelectric impedance assessment (BIA) based on AWGS definition. The participants failed in AWGS algorithm will be invited to join the research. Exclusion criteria are those with (1)pathological bone diseases, (2) chronic inflammatory conditions (e.g. rheumatoid arthritis), (3) neurological problems affecting gait, (4) taking regular supervised exercise training for more than 3 times/week, (5) chair-bound or bed-bound, and (6) malignancy.

Recruited subjects will be randomized to either (1) Control, (2) HMB only, (3) VT only or (4) HMB +VT group. All subjects will be given protein supplement to ensure minimal daily protein intake. Subject assigned to VT group will receive VT (35Hz, 0.3g, 20min/day, at least 3 times/week) for 6 months. Subjects assigned to HMB group will take HMB capsules 3g/day for 6 months. Subjects assigned to HMB+VT group will recieve both VT and HMB supplements for 6 months. The primary outcome is muscle strength showing subjects' functional ability. All primary and secondary outcome assessments for all groups will be performed in the investigators' institute at baseline, 3 months and 6 months post-treatment.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Wing Hoi Cheung, PhD; Phone Number: 35052715; Email: louischeung@cuhk.edu.hk
• Study Contact Backup: Name: Meng Chen Michelle Li, PhD; Phone Number: 35053312; Email: michellemcli@cuhk.edu.hk

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • The Chinese University of Hong Kong Jockey Club Centre for Osteoporosis Care and Control
    • Contact: Zhihui Lu, PhD; Email: anjolu@cuhk.edu.hk
    • Principal Investigator: Timothy Chi Yui Kwok, PhD
  • Hong Kong, Hong Kong
    • Active, not recruiting
    • Evangelical Luthera Church Social Service - Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • The Chinese University of Hong Kong, Department of Orthopaedics and Traumatology, 1/F Li Ka Shing Outpatient Clinic (North), PWH
    • Contact: Meng Chen Michelle Li, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects aged 60 years or above

• Subjects failed in AWGS algorithm

  1. skeletal muscle mass by BIA (male at <7.0 kg/m^2, female at <5.7 kg/m^2), and
  2. handgrip strength (male at <28 kg, female at <18kg), and/or
  3. gait speed test (>1m/s)

Exclusion Criteria:

• Subjects with pathological bone diseases
• Subjects with chronic inflammatory condition (e.g. rheumatoid arthritis)
• Subjects with neurological problems
• Subjects receiving regular exercise
• Subjecs who are chair-/bed- bound
• Subjects with malignancy
• Subjects with cardiovascular concern such as with pace-maker in-situ
• Subjects with acute fractures or severe osteoarthritis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control Group; Subjects assigned to Contro Group will not receive VT or HMB. They will receive daily protein supplement for 6 months.	Dietary supplement: Protein supplement; Daily protein supplement intake
Active Comparator: HMB only Group; Subjects assigned to HMB only Group will receive HMB supplement at 3g/day and daily protein supplement for 6 months.	Dietary supplement: Protein supplement; Daily protein supplement intake; Dietary supplement: β-hydroxy β-methylbutyrate (HMB) supplement; Oral nutritional HMB supplement at 3g/day
Active Comparator: VT only Group; Subjects assigned to VT only Group will receive VT (0.3g, 35Hz, at least 3 times/week) and daily protein supplement for 6 months	Dietary supplement: Protein supplement; Daily protein supplement intake; Device: Low-magnitude High-frequency Vibration; 0.3g, 35Hz, 20mins/day, at least 3 times/week; Other Names: Vibration Treatment
Experimental: HMB + VT Group; Subjects assigned to HMB + VT Group will receive HMB supplement at 3g/day, VT at least 3 times/week and daily protein supplement for 6 months.	Dietary supplement: Protein supplement; Daily protein supplement intake; Dietary supplement: β-hydroxy β-methylbutyrate (HMB) supplement; Oral nutritional HMB supplement at 3g/day; Device: Low-magnitude High-frequency Vibration; 0.3g, 35Hz, 20mins/day, at least 3 times/week; Other Names: Vibration Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle strength-handgrip	Handgrip strength will be measured by a dynamometer on each hand of the subject.	6 months
Muscle performance-gait speed	Gait speed will be assessed by a 6-meter-walk test.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dual energy x-ray absortiometry (DXA)	Whole body muscle mass measurement	6 months
Time-up-and-go test (TUG)	Time will be recorded for participants to rise from a chair, walk 3 meters, turn around, and walk back to the chair then sitting down	6 months
Biodex Balance System-LOS	Limits of stability will be recorded to evaluate the dynamic posture stability. Maximum scores will be 100 where the higher scores indicate better performance.	6 months
Biodex Balance System-OSI	Posture stability (Overall Stability Index) will be recorded. High scores indicate poorer balancing abillity.	6 months
36-item Short-Form Health Survey (SF-36)	Health-related quality of life will be assessed by the validated Chinese version of SF-36. Scores range from 0 to 100 where higher scores indicate better health status	6 months

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Collaborators: Abbott
• Investigators: Principal Investigator: Wing Hoi Cheung, PhD, Chinese University of Hong Kong

Publications and helpful links

General Publications

• Leung KS, Li CY, Tse YK, Choy TK, Leung PC, Hung VW, Chan SY, Leung AH, Cheung WH. Effects of 18-month low-magnitude high-frequency vibration on fall rate and fracture risks in 710 community elderly--a cluster-randomized controlled trial. Osteoporos Int. 2014 Jun;25(6):1785-95. doi: 10.1007/s00198-014-2693-6. Epub 2014 Mar 28.
• Deutz NE, Pereira SL, Hays NP, Oliver JS, Edens NK, Evans CM, Wolfe RR. Effect of beta-hydroxy-beta-methylbutyrate (HMB) on lean body mass during 10 days of bed rest in older adults. Clin Nutr. 2013 Oct;32(5):704-12. doi: 10.1016/j.clnu.2013.02.011. Epub 2013 Mar 4.
• Cheung WH, Mok HW, Qin L, Sze PC, Lee KM, Leung KS. High-frequency whole-body vibration improves balancing ability in elderly women. Arch Phys Med Rehabil. 2007 Jul;88(7):852-7. doi: 10.1016/j.apmr.2007.03.028.
• Zhu LY, Chan R, Kwok T, Cheng KC, Ha A, Woo J. Effects of exercise and nutrition supplementation in community-dwelling older Chinese people with sarcopenia: a randomized controlled trial. Age Ageing. 2019 Mar 1;48(2):220-228. doi: 10.1093/ageing/afy179.
• Chen LK, Liu LK, Woo J, Assantachai P, Auyeung TW, Bahyah KS, Chou MY, Chen LY, Hsu PS, Krairit O, Lee JS, Lee WJ, Lee Y, Liang CK, Limpawattana P, Lin CS, Peng LN, Satake S, Suzuki T, Won CW, Wu CH, Wu SN, Zhang T, Zeng P, Akishita M, Arai H. Sarcopenia in Asia: consensus report of the Asian Working Group for Sarcopenia. J Am Med Dir Assoc. 2014 Feb;15(2):95-101. doi: 10.1016/j.jamda.2013.11.025.
• Wang J, Cui C, Chim YN, Yao H, Shi L, Xu J, Wang J, Wong RMY, Leung KS, Chow SK, Cheung WH. Vibration and beta-hydroxy-beta-methylbutyrate treatment suppresses intramuscular fat infiltration and adipogenic differentiation in sarcopenic mice. J Cachexia Sarcopenia Muscle. 2020 Apr;11(2):564-577. doi: 10.1002/jcsm.12535. Epub 2020 Jan 28.

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2023
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: August 30, 2022
• First Submitted That Met QC Criteria: August 30, 2022
• First Posted (Actual): September 1, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 12, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Sarcopenia; Vibration; Hydroxymethylbutyrate
• Additional Relevant MeSH Terms: Neurologic Manifestations; Musculoskeletal Diseases; Nervous System Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Congenital Abnormalities; Muscular Atrophy; Atrophy; Sarcopenia; Connective Tissue Diseases; Musculoskeletal Abnormalities
• Other Study ID Numbers: CREC 2022.233-T

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No