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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Sarcopenia, Connective Tissue Diseases in Old Age, Musculoskeletal Abnormalities

Intervention / Treatment
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* Device: Low-magnitude High-frequency Vibration
* Dietary Supplement: β-hydroxy β-methylbutyrate (HMB) supplement
* Dietary Supplement: Protein supplement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects aged 65 years or above Subjects failed in AWGS algorithm skeletal muscle mass by BIA (male at <7.0 kg/m^2, female at <5.7 kg/m^2), and handgrip strength (male at <26 kg, female at <18kg), and/or 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

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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.
Masking: Single


Arms and Interventions

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

What is the study measuring?
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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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sarcopenia, Vibration, Hydroxymethylbutyrate