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RecruitingNCT07597850TCM-HMB-PFUpdated May 19, 2026

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

A Phase 2 interventional study of TCM Formula and HMB (beta-Hydroxy-beta-methylbutyrate) in Pre-Frailty, Sarcopenia and Muscle Atrophy or Weakness, sponsored by Tri-Service General Hospital (TSGH). Recruiting at 1 site in Taiwan. Open to participants aged 65 Years and older. Per ClinicalTrials.gov, last updated 2026-05-19.

Sponsored by Tri-Service General Hospital (TSGH) · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
90
Allocation
Randomized
Ages
65 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Pre-Frailty
  • Sarcopenia
  • Muscle Atrophy or Weakness
  • Osteoporosis
  • Aging

Keywords

  • Traditional Chinese Medicine
  • HMB (Hydroxy-beta-methylbutyrate)
  • Muscle Strength
  • Handgrip Strength
  • Body Composition
  • Elderly Health
  • Randomized Controlled Trial
03

Who can participate

Ages eligible
65 Years and older
Sexes eligible
All
Accepts 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

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.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
90 participants (estimated)

Study arms

  • Experimental
    Experimental: TCM Group

    Participants will receive a standardized Traditional Chinese Medicine herbal powder formula. This formula is designed to tonify Qi, Blood, Liver, and Kidney to enhance physical function in elders. The daily dosage is 18 grams, administered as one 9-gram sachet twice daily. It is taken 30 minutes before breakfast and lunch for 24 consecutive weeks.

    Drug: TCM Formula

  • Active comparator
    Active Comparator: HMB Group

    Participants will receive beta-hydroxy-beta-methylbutyrate (HMB) as an active control. The intervention consists of a total daily dose of 3 grams, administered as two 0.75-gram tablets twice daily. The tablets are to be taken after breakfast and lunch for 24 consecutive weeks.

    Dietary Supplement: HMB (beta-Hydroxy-beta-methylbutyrate)

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.

    Also known as: TCM

  • 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.

    Also known as: HMB

05

What researchers measure

Primary outcomes

  1. Change from Baseline in Hand Grip Strength at 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.

    Time frame: Baseline and Week 12

Secondary outcomes

  1. Change in Hand Grip Strength at 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.

    Time frame: Baseline and Week 24.

  2. Change in Skeletal Muscle Mass

    Change from baseline in skeletal muscle mass measured by Bioelectrical Impedance Analysis (BIA). This reflects structural changes in muscle quantity.

    Time frame: Baseline, Week 12, and Week 24.

  3. Change in Calf Circumference

    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.

    Time frame: Baseline, Week 12, and Week 24.

  4. Change in Gait Speed

    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.

    Time frame: Baseline, Week 12, and Week 24.

  5. Change in Timed Up and Go (TUG) Test Time

    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.

    Time frame: Baseline, Week 12, and Week 24.

  6. Change in Five Times Sit-to-Stand (5xSTS) Test Time

    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.

    Time frame: Baseline, Week 12, and Week 24.

  7. Change in Fried Frailty Phenotype Status

    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.

    Time frame: Baseline, Week 12, and Week 24.

  8. Change in Clinical Frailty Scale (CFS) Score

    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.

    Time frame: Baseline, Week 12, and Week 24.

  9. Change in Bone Mineral Density (BMD)

    Change from baseline in bone mineral density measured by Dual-energy X-ray Absorptiometry (DXA, Lunar iDXA).

    Time frame: Baseline, Week 12, and Week 24.

  10. Change in Body Fat Percentage

    Change from baseline in body fat percentage analyzed using DXA (Lunar iDXA). This reflects changes in body composition related to metabolic health.

    Time frame: Baseline, Week 12, and Week 24.

  11. Change in SF-12 Quality of Life Score

    Change from baseline in the 12-Item Short Form Health Survey (SF-12) scores. Higher scores represent better health-related quality of life.

    Time frame: Baseline, Week 12, and Week 24.

Other outcomes

  1. Incidence of Treatment-Emergent Adverse Events (Safety)

    Number of participants with treatment-emergent adverse events (AEs) and serious adverse events (SAEs) . AEs will be assessed for severity (mild, moderate, or severe) and their causal relationship to the study interventions (TCM formula or HMB supplement).

    Time frame: Baseline up to Week 24.

  2. Number of Participants With Clinically Significant Laboratory Abnormalities

    Number of participants with laboratory values that are outside the reference range and judged by the investigator to be clinically significant. Laboratory assessments include: Complete Blood Count (CBC); Liver function (ALT, AST, Albumin); Renal function (BUN, Creatinine, eGFR, Uric acid); Electrolytes (Na, K, Ca, Mg); Fasting blood glucose; and General Urinalysis (protein, glucose, urobilinogen, bilirubin, sediment, specific gravity, pH, occult blood) .

    Time frame: Baseline up to Week 24

06

Study locations

1 of 1 sites recruiting
  • Tri-Service General Hospital
    Taipei, 114202, Taiwan
    • Jui-Shan Lin, MD · Contact · sunnylin@mail.ndmutsgh.edu.tw · 886-2-87923311
    • Jui-Shan Lin, MD · Principal investigator
    • Li-Wei Wu, MD · Sub investigator
    • Sui-Lung Su, Prof. · Sub investigator
    • Wen-Hui Fang, MD · Sub investigator
    • Yaw-Wen Chang, MD · Sub investigator
    • Tung-Wei Kao, MD · Sub investigator
    • Hung-Yi Chen, MD · Sub investigator
    • Yan-Ru Wang, MD · Sub investigator
    • Yu-Heng Wang, MD · Sub investigator
    • Po-Han Lin, MD · Sub investigator
    • Tao-Chun Peng, MD · Sub investigator
    • Ting-Ching Chen, MD · Sub investigator
    • Wan-Ting Soong, MD · Sub investigator
    • Yu-Ting Cheng, MD · Sub investigator
    • Yi-Ru Lei, MD · Sub investigator
    Recruiting
07

References and documents

Publications

  • Yoo JI, Choi H, Ha YC. Mean Hand Grip Strength and Cut-off Value for Sarcopenia in Korean Adults Using KNHANES VI. J Korean Med Sci. 2017 May;32(5):868-872. doi: 10.3346/jkms.2017.32.5.868. PubMed 28378563 ↗
  • Soares LA, Lima LP, Prates ACN, Arrieiro AN, Da Costa Teixeira LA, Duarte TC, Dos Santos JM, da Silva Lage VK, de Paula FA, Costa HS, Figueiredo PHS, de Almeida VMTL, de Sara Abreu N, Costa SP, Brant FP, Lima RR, Thomasini RL, Pereira LSM, Pereira FSM, Parentoni AN, de Avelar NCP, Leopoldino AAO, Mendonca VA, Lacerda ACR. Accuracy of handgrip and respiratory muscle strength in identifying sarcopenia in older, community-dwelling, Brazilian women. Sci Rep. 2023 Jan 27;13(1):1553. doi: 10.1038/s41598-023-28549-5. PubMed 36707661 ↗
  • Blanquet M, Ducher G, Sauvage A, Dadet S, Guiyedi V, Farigon N, Guiguet-Auclair C, Berland P, Bohatier J, Boirie Y, Gerbaud L. Handgrip strength as a valid practical tool to screen early-onset sarcopenia in acute care wards: a first evaluation. Eur J Clin Nutr. 2022 Jan;76(1):56-64. doi: 10.1038/s41430-021-00906-5. Epub 2021 Apr 13. PubMed 33850314 ↗
  • Vaishya R, Misra A, Vaish A, Ursino N, D'Ambrosi R. Hand grip strength as a proposed new vital sign of health: a narrative review of evidences. J Health Popul Nutr. 2024 Jan 9;43(1):7. doi: 10.1186/s41043-024-00500-y. PubMed 38195493 ↗
  • Dwimartutie N, Setiati S, Tamin TZ, Prijanti AR, Harahap AR, Purnamasari D, Harimurti K, Pramantara IDP, Suwarto S, Kojima T. Effect of cholecalciferol supplementation on hand grip strength, walking speed, and expression of vitamin D receptor, interleukin-6, and insulin-like growth factor-1 in monocyte in pre-frail older adults: A randomized double-blind placebo-controlled trial. Geriatr Gerontol Int. 2024 Jun;24(6):554-562. doi: 10.1111/ggi.14881. Epub 2024 Apr 21. PubMed 38644647 ↗
  • Castell MV, Sanchez M, Julian R, Queipo R, Martin S, Otero A. Frailty prevalence and slow walking speed in persons age 65 and older: implications for primary care. BMC Fam Pract. 2013 Jun 19;14:86. doi: 10.1186/1471-2296-14-86. PubMed 23782891 ↗
  • Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA; Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001 Mar;56(3):M146-56. doi: 10.1093/gerona/56.3.m146. PubMed 11253156 ↗
  • Nari F, Park EC, Nam CM, Jang SI. Impact of frailty on mortality and healthcare costs and utilization among older adults in South Korea. Sci Rep. 2023 Dec 1;13(1):21203. doi: 10.1038/s41598-023-48403-y. PubMed 38040759 ↗
  • Alvarez-Bustos A, Rodriguez-Sanchez B, Carnicero-Carreno JA, Sepulveda-Loyola W, Garcia-Garcia FJ, Rodriguez-Manas L. Healthcare cost expenditures associated to frailty and sarcopenia. BMC Geriatr. 2022 Sep 13;22(1):747. doi: 10.1186/s12877-022-03439-z. PubMed 36096728 ↗
  • Peng LN, Cheng YC, Yu PC, Lee WJ, Lin MH, Chen LK. Oral Nutritional Supplement with beta-hydroxy-beta-methylbutyrate (HMB) Improves Nutrition, Physical Performance and Ameliorates Intramuscular Adiposity in Pre-Frail Older Adults: A Randomized Controlled Trial. J Nutr Health Aging. 2021;25(6):767-773. doi: 10.1007/s12603-021-1621-7. PubMed 34179932 ↗
  • Yang C, Song Y, Li T, Chen X, Zhou J, Pan Q, Jiang W, Wang M, Jia H. Effects of Beta-Hydroxy-Beta-Methylbutyrate Supplementation on Older Adults with Sarcopenia: A Randomized, Double-Blind, Placebo-Controlled Study. J Nutr Health Aging. 2023;27(5):329-339. doi: 10.1007/s12603-023-1911-1. PubMed 37248756 ↗
  • Takayama S, Tomita N, Arita R, Ono R, Kikuchi A, Ishii T. Kampo Medicine for Various Aging-Related Symptoms: A Review of Geriatric Syndrome. Front Nutr. 2020 Jul 15;7:86. doi: 10.3389/fnut.2020.00086. eCollection 2020. PubMed 32766269 ↗
  • Buto MSS, de Oliveira MPB, Carvalho C, Vassimon-Barroso V, Takahashi ACM. Effect of complementary therapies on functional capacity and quality of life among prefrail and frail older adults: A systematic review of randomized controlled trials. Arch Gerontol Geriatr. 2020 Nov/Dec;91:104236. doi: 10.1016/j.archger.2020.104236. Epub 2020 Aug 21. PubMed 32860990 ↗
  • Yakabe M, Hosoi T, Sasakawa H, Akishita M, Ogawa S. Kampo formula hochu-ekki-to (Bu-Zhong-Yi-Qi-Tang, TJ-41) ameliorates muscle atrophy by modulating atrogenes and AMPK in vivo and in vitro. BMC Complement Med Ther. 2022 Dec 28;22(1):341. doi: 10.1186/s12906-022-03812-w. PubMed 36578084 ↗
  • Schonenberg A, Heimrich KG, Sternkopf A, Lochbihler P, Prell T. Patient-reported geriatric syndromes and their association with quality of life: findings from a cross-sectional study in German older adults. Eur Geriatr Med. 2026 Apr;17(2):721-733. doi: 10.1007/s41999-025-01332-7. Epub 2025 Oct 16. PubMed 41099789 ↗

Individual participant data

Plan to share: No — Individual participant data collected during the trial will not be shared with the general public. According to the study protocol, all research data and intellectual property are jointly owned by the National Research Institute of Chinese Medicine and Tri-Service General Hospital. To protect participant privacy and maintain strict confidentiality, access to de-identified participant data is limited to the principal investigator and authorized research team members. Direct access to original records is permitted only for the trial sponsor, the Institutional Review Board, and regulatory authorities for the purposes of monitoring and auditing to ensure compliance with Good Clinical Practice and relevant data protection laws. There is currently no plan to make the individual participant data available to external researchers or the public to maintain the highest standards of participant confidentiality and protect the research interests of the participating institutions.

08

Registry details

Key details

Study ID
NCT07597850
Lead sponsor
Tri-Service General Hospital (TSGH)
Collaborators
National Research Institute of Chinese Medicine, Ministry of Health and Welfare
Responsible party
Jui-Shan Lin, MD (Attending Physician, Tri-Service General Hospital (TSGH)) — Principal investigator
First posted
May 19, 2026
Start date
Apr 2, 2026
Primary completion
Oct 31, 2026 (estimated)
Completion
Dec 31, 2026 (estimated)
Last update
May 19, 2026

Study contacts

Jui-Shan Lin, MD
Contact
sunnylin@mail.ndmutsgh.edu.tw
886-2-87923311 ext. 24260
Li-Wei Wu, MD
Contact
liweiwu@mail.ndmutsgh.edu.tw
886-2-87923311 ext. 12618
Jui-Shan Lin, MD
principal investigator · Tri-Service General Hospital (TSGH)

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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