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

Sarcopenia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05525039
• Other study ID #: CREC 2022.233-T
• Status: Recruiting
• Phase: N/A
• Start date: January 12, 2023
• Est. completion date: April 2025

Study information

• Verified date: February 2023
• Source: Chinese University of Hong Kong
• Contact: Wing Hoi Cheung, PhD
• Phone: 35052715
• Email: louischeung[@]cuhk.edu.hk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: April 2025
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

• Subjects aged 65 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 <26 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

Related Conditions & MeSH terms

• Connective Tissue Diseases
• Musculoskeletal Abnormalities
• Sarcopenia

Intervention

Device:
• Low-magnitude High-frequency Vibration
0.3g, 35Hz, 20mins/day, at least 3 times/week

Dietary Supplement:
• ß-hydroxy ß-methylbutyrate (HMB) supplement
Oral nutritional HMB supplement at 3g/day
• Protein supplement
Daily protein supplement intake

Locations

Country	Name	City	State
Hong Kong	Evangelical Luthera Church Social Service - Hong Kong	Hong Kong
Hong Kong	The Chinese University of Hong Kong Jockey Club Centre for Osteoporosis Care and Control	Hong Kong
Hong Kong	The Chinese University of Hong Kong, Department of Orthopaedics and Traumatology, 1/F Li Ka Shing Outpatient Clinic (North), PWH	Hong Kong

Sponsors (2)

Lead Sponsor	Collaborator
Chinese University of Hong Kong	Abbott

Country where clinical trial is conducted

Hong Kong, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Muscle strength-handgrip	Handgrip strength will be measured by a dynamometer on each hand of the subject.	6 months
Primary	Muscle performance-gait speed	Gait speed will be assessed by a 6-meter-walk test.	6 months
Secondary	Dual energy x-ray absortiometry (DXA)	Whole body muscle mass measurement	6 months
Secondary	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
Secondary	Biodex Balance System-OSI	Posture stability (Overall Stability Index) will be recorded. High scores indicate poorer balancing abillity.	6 months
Secondary	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
Secondary	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