TCM Formula vs. HMB in Pre-Frail Elders: Muscle Strength and Bone Status

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.

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.