Aging, Muscle Atrophy or Weakness, Osteoporosis, Pre-Frailty, Sarcopenia
Conditions
Keywords
Traditional Chinese Medicine, HMB (Hydroxy-beta-methylbutyrate), Muscle Strength, Handgrip Strength, Body Composition, Elderly Health, Randomized Controlled Trial
Brief summary
The purpose of this study is to compare the effects of a standardized Traditional Chinese Medicine (TCM) formula versus beta-hydroxy-beta-methylbutyrate (HMB) on muscle strength and bone health in pre-frail older adults . Pre-frailty is a critical stage where functional decline may still be reversed through proper intervention. The study will enroll 90 participants aged 65 years or older who meet the criteria for pre-frailty. Participants will be randomly assigned to either the TCM group (receiving a standardized herbal powder formula) or the HMB group (receiving nutritional supplement tablets) for 24 weeks . The primary objective is to evaluate the change in handgrip strength from baseline to Week 12 . Researchers will also assess changes in skeletal muscle mass, bone mineral density, and overall physical performance . The goal is to determine if the TCM formula is an effective alternative or complementary intervention for managing geriatric frailty.
Detailed description
This is a randomized, open-label, parallel-group comparative study designed to evaluate the clinical efficacy and safety of a standardized Traditional Chinese Medicine formula versus beta-hydroxy-beta-methylbutyrate supplementation in pre-frail older adults . Pre-frailty is identified as a reversible stage between robust health and frailty. This study aims to provide clinical evidence for the Traditional Chinese Medicine formula as an intervention to improve muscle strength, bone health, and physical function. Eligible participants aged 65 years or older who meet 1 to 2 of the 5 Fried frailty phenotype criteria will be randomized in a 1 to 1 ratio. The total study duration for each participant is approximately 26 weeks, including a screening period and a 24-week intervention period. Participants in the Traditional Chinese Medicine group receive a standardized herbal powder formula designed to tonify Qi, Blood, Liver, and Kidney. The total daily dosage is 18 grams, administered as 9 grams twice daily, taken 30 minutes before breakfast and lunch. Participants in the HMB group receive a total daily dose of 3 grams of beta-hydroxy-beta-methylbutyrate, administered as two 0.75-gram tablets twice daily after breakfast and lunch. The primary endpoint is the change from baseline in handgrip strength at Week 12 . Secondary endpoints assessed at Week 12 and Week 24 include changes in skeletal muscle mass, bone mineral density, body fat percentage, gait speed using a 6-meter test, Timed Up and Go test, Five Times Sit-to-Stand test, Fried frailty phenotype status, Clinical Frailty Scale scores, and SF-12 quality of life scores . Safety is monitored throughout the study by assessing adverse events and changes in laboratory parameters, including complete blood count, liver and renal function, and urinalysis . A total of 90 participants (45 per group) is required based on a non-inferiority t-test for the primary endpoint. The calculation assumed a power of 80 percent and a one-sided significance level of 0.025, accounting for an estimated 20 percent dropout rate.
Interventions
DRUGTCM Formula
A scientific TCM herbal powder formula prepared by the hospital pharmacy. The formula consists of 10 botanical ingredients focused on tonifying Qi, Blood, Liver, and Kidney. Participants will receive a total daily dose of 18 grams, administered as 9 grams twice daily (BID), 30 minutes before breakfast and lunch.
DIETARY_SUPPLEMENTHMB (beta-Hydroxy-beta-methylbutyrate)
The active ingredient is beta-hydroxy-beta-methylbutyrate (HMB), provided in 0.75g tablets. Participants will take 2 tablets twice daily (BID) after breakfast and lunch, resulting in a total daily dose of 3 grams. This is a common clinical dose used as a nutritional intervention for muscle strength and physical performance.
Sponsors
Tri-Service General Hospital
National Research Institute of Chinese Medicine, Ministry of Health and Welfare
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is an open-label study. Due to the distinct physical characteristics of the interventions (TCM vs. HMB nutritional supplement), masking of participants and investigators is not feasible.
Intervention model description
Randomized, parallel-group, active-controlled study with a 1:1 allocation ratio.
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female participants aged 65 years or older at the time of screening. * Body Mass Index less than 30 kilograms per square meter. * Identified as pre-frail according to the Fried frailty phenotype, meeting 1 to 2 of the following 5 criteria: 1) Hand grip strength below specific thresholds based on gender and Body Mass Index. For males, Body Mass Index 24 or less is 29 kilograms or less, Body Mass Index 24.1 to 28 is 30 kilograms or less, Body Mass Index greater than 28 is 32 kilograms or less. For females, Body Mass Index 23 or less is 17 kilograms or less, Body Mass Index 23.1 to 26 is 17.3 kilograms or less, Body Mass Index 26.1 to 29 is 18 kilograms or less, Body Mass Index greater than 29 is 21 kilograms or less. 2) Slow walking speed. For a 4-meter distance, walking time of 7 seconds or more for males 173 centimeters or shorter, or 6 seconds or more for males taller than 173 centimeters. For females 159 centimeters or shorter, 7 seconds or more, or 6 seconds or more for females taller than 159 centimeters. 3) Self-reported exhaustion. Answering 3 days or more per week to either feeling that everything was an effort or could not get going in the past week. 4) Unintentional weight loss. Loss of 3 kilograms or more or more than 5 percent of body weight in the past year. 5) Low physical activity. Weekly energy expenditure less than 383 kilocalories for males or less than 270 kilocalories for females. * Ability to safely complete a 6-meter walk test in a single attempt without assistance or using only simple aids such as a cane. * Clinically stable condition allowing for follow-up visits every 4 weeks and participation in all study-related assessments. * Willingness to provide existing test data from within 90 days prior to randomization, including Bone Mineral Density by DXA and serum biochemistry or urinalysis results. * Sufficient cognitive function to understand the study and sign the informed consent form, or with the assistance of a legal representative. * Willingness to maintain existing diet and exercise habits during the study and not start high-intensity exercise programs or large amounts of nutritional supplements.
Exclusion criteria
* Major acute illness such as acute myocardial infarction, pneumonia, or acute stroke within 2 weeks prior to screening. * Major organ dysfunction, including renal function with estimated glomerular filtration rate less than 45 milliliters per minute per 1.73 square meters within 1 month prior to screening, liver function with AST or ALT greater than 3 times the upper limit of normal within 1 month prior to screening, NYHA Class III or IV heart failure, or severe COPD requiring long-term oxygen therapy. * Unplanned hospitalization within 1 month prior to screening, or major surgery with incomplete functional recovery within 3 months prior to screening. * Current malignant tumor under treatment, or less than 12 months since the completion of cancer treatment. * Use of supplements containing the same ingredients as the study interventions, or products that may affect the primary endpoint including HMB, creatine, branched-chain amino acids, or high-dose protein powder within 4 weeks prior to screening. * Known significant clinical allergy or hypersensitivity to any components of the study formula or HMB nutritional supplement. * Moderate to severe dementia, severe depression, or other psychiatric disorders resulting in inability to cooperate without a legal representative. * Participation in other interventional clinical trials involving drugs, biologics, or nutritional supplements within 3 months prior to screening. * New initiation or dose adjustment of medications affecting muscle or bone metabolism within 3 months prior to screening, including systemic glucocorticoids, anabolic steroids, testosterone, or growth hormones. * Any other condition that, in the opinion of the investigator, makes the participant unsuitable for the study due to safety or compliance concerns.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Hand Grip Strength at Week 12 | Baseline and Week 12 | Hand grip strength is used as a functional biomarker to reflect overall muscle strength. Measurement will be performed using a standardized JAMAR dynamometer. Participants will follow a standardized procedure: seated position, elbow flexed at 90 degrees, with the forearm in a neutral position using the dominant hand. The "Change" is calculated as the value at Week 12 minus the baseline value . Higher values indicate improved muscle strength. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hand Grip Strength at Week 24 | Baseline and Week 24. | Change from baseline in hand grip strength at Week 24. Measurement is performed using a standardized JAMAR dynamometer with the dominant hand. Higher values indicate better muscle strength. |
| Change in Skeletal Muscle Mass | Baseline, Week 12, and Week 24. | Change from baseline in skeletal muscle mass measured by Bioelectrical Impedance Analysis (BIA). This reflects structural changes in muscle quantity. |
| Change in Calf Circumference | Baseline, Week 12, and Week 24. | Change from baseline in calf circumference measured at the widest part of the calf using a soft tape. It serves as a proxy indicator for lower limb muscle mass. |
| Change in Gait Speed | Baseline, Week 12, and Week 24. | Change from baseline in gait speed using the 6-meter gait speed test. Participants walk at a normal pace, and the time taken is recorded to reflect functional mobility. |
| Change in Timed Up and Go (TUG) Test Time | Baseline, Week 12, and Week 24. | Change from baseline in the time required to rise from a chair, walk 3 meters, turn, return, and sit down again. This test evaluates dynamic balance and agility. |
| Change in Five Times Sit-to-Stand (5xSTS) Test Time | Baseline, Week 12, and Week 24. | Change from baseline in the time taken to complete five consecutive sit-to-stand cycles as quickly as possible. This reflects lower limb muscle power and endurance. |
| Change in Fried Frailty Phenotype Status | Baseline, Week 12, and Week 24. | Change from baseline in frailty status categorized as Robust (0 criteria), Pre-frail (1-2 criteria), or Frail (3-5 criteria) based on 5 indicators: grip strength, walking speed, exhaustion, weight loss, and physical activity. |
| Change in Clinical Frailty Scale (CFS) Score | Baseline, Week 12, and Week 24. | Change from baseline in the Clinical Frailty Scale score, which ranges from 1 (Very Fit) to 9 (Terminally Ill). It provides a holistic clinical assessment of frailty level. |
| Change in Bone Mineral Density (BMD) | Baseline, Week 12, and Week 24. | Change from baseline in bone mineral density measured by Dual-energy X-ray Absorptiometry (DXA, Lunar iDXA). |
| Change in Body Fat Percentage | Baseline, Week 12, and Week 24. | Change from baseline in body fat percentage analyzed using DXA (Lunar iDXA). This reflects changes in body composition related to metabolic health. |
| Change in SF-12 Quality of Life Score | Baseline, Week 12, and Week 24. | Change from baseline in the 12-Item Short Form Health Survey (SF-12) scores. Higher scores represent better health-related quality of life. |
Countries
Taiwan
Contacts
CONTACTJui-Shan Lin, MD
CONTACTLi-Wei Wu, MD
PRINCIPAL_INVESTIGATORJui-Shan Lin, MD
Tri-Service General Hospital
Outcome results
None listed