Sarcopenia
Conditions
Keywords
Traditional Chinese Medicine, Shanyu Pill, Gut Microbiota, Gut-Muscle-Brain Axis, Functional Near-Infrared Spectroscopy, Untargeted Metabolomics, Dual-Task Gait, Cognitive Function
Brief summary
Sarcopenia is an age-related condition characterized by progressive loss of muscle mass, muscle strength, and physical function. It may also be associated with impaired cognitive function. Effective treatment options for sarcopenia remain limited. This multicenter, randomized, double-blind, placebo-controlled clinical trial is designed to evaluate the effects of Shanyu Pill in older adults with sarcopenia. A total of 192 participants are randomly assigned in a 1:1 ratio to receive either Shanyu Pill or placebo for 24 weeks. A long-term follow-up assessment is scheduled 2 years after completion of the 24-week intervention. The primary outcome is the change in appendicular skeletal muscle mass index (ASMI) from baseline to week 24. Other assessments include muscle strength, physical performance, cognitive function, and traditional Chinese medicine syndrome severity assessed using the Spleen Qi Deficiency Syndrome Score. Musculoskeletal ultrasound, functional near-infrared spectroscopy, gut microbiota analysis, and untargeted metabolomics are also used in subsets of participants to explore potential mechanisms associated with the effects of Shanyu Pill, including possible interactions within the gut-muscle-brain axis.
Detailed description
This is a multicenter, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy of Shanyu Pill and explore its potential mechanisms in older adults with sarcopenia and spleen qi deficiency syndrome. The trial includes a total of 192 participants, who are randomly assigned in a 1:1 ratio to receive either Shanyu Pill or placebo. The trial is conducted at three study centers in China: the Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, the Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine, and the Health Examination Center of the Sixth Affiliated Hospital of Sun Yat-sen University. Eligible participants are screened according to predefined inclusion and exclusion criteria, and written informed consent is obtained before enrollment. The randomization sequence is generated by independent statistical personnel who are not involved in participant recruitment, intervention delivery, or outcome assessment. Participants, investigators, and outcome assessors are blinded to treatment allocation. Shanyu Pill is a traditional Chinese medicine formula consisting mainly of Chinese yam, Atractylodes macrocephala, and ginseng. The placebo is primarily composed of corn starch and dextrin and is designed to resemble Shanyu Pill in appearance, shape, size, color, specification, packaging, and labeling to maintain blinding. Participants in both groups receive the assigned study medication orally three times daily, 5 days per week, for 24 weeks. Standardized health education is provided to both groups once per month during the intervention period. Clinical assessments are scheduled at baseline, week 12, week 24, and 2 years after completion of the 24-week intervention. The assessment conducted 2 years after completion of the intervention is designed to evaluate long-term outcomes. The primary outcome is the change in appendicular skeletal muscle mass index (ASMI) from baseline to week 24. Secondary outcomes include handgrip strength, five-times sit-to-stand test performance, gait speed, 6-minute walk distance, Short Physical Performance Battery (SPPB) score, Timed Up and Go test completion time, Montreal Cognitive Assessment (MoCA) score, Stroop Color-Word Test completion time and accuracy, and traditional Chinese medicine syndrome severity assessed using the Spleen Qi Deficiency Syndrome Score. Mechanistic assessments are performed in subsets of participants. Musculoskeletal ultrasound is used to assess skeletal muscle morphology and related characteristics. Functional near-infrared spectroscopy (fNIRS), combined with motor-cognitive dual-task gait assessments, is used to investigate cortical hemodynamic responses and their associations with clinical outcomes. Gut microbiota profiling using 16S rRNA gene sequencing and untargeted metabolomic analyses of serum and fecal samples are also performed in subsets of participants to characterize changes in gut microbial composition and metabolic profiles. The fNIRS, gut microbiota, and metabolomic assessments are scheduled at baseline, week 24, and 2 years after completion of the 24-week intervention. These assessments are used to explore potential biological mechanisms associated with the effects of Shanyu Pill, including possible interactions among the gut, skeletal muscle, and brain. The study protocol is approved by the Medical Ethics Committee of the Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine (Approval No. SPHFJP-T2023007-02), the Ethics Committee of the Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine (Approval No. 2023KY-051-001), and the Ethics Committee of the Sixth Affiliated Hospital of Sun Yat-sen University (Approval No. 2023ZSLYEC-669).
Interventions
DIETARY_SUPPLEMENTShanyu pill
It consists of Chinese yam, Atractylodes macrocephala, and ginseng.
DIETARY_SUPPLEMENTPlacebo
It consists of corn starch and dextrin
Sponsors
Fujian University of Traditional Chinese Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Age 60-85 years; meeting the Asian Working Group for Sarcopenia (AWGS) diagnostic criteria for sarcopenia and the traditional Chinese medicine diagnostic criteria for spleen qi deficiency syndrome. 2. Able to understand and cooperate with study procedures and voluntarily provide written informed consent.
Exclusion criteria
1. Severe neurological or musculoskeletal disorders that may affect motor function, including severe osteoporosis or severe osteoarthritis. 2. Severe cardiovascular, pulmonary, or psychiatric disorders; uncontrolled endocrine or metabolic diseases; or severe hepatic or renal dysfunction, including cirrhosis, renal failure, or dialysis. 3. Inability to communicate effectively with the investigators because of speech impairment or uncorrected hearing impairment. 4. Severe cognitive impairment, defined as a Montreal Cognitive Assessment (MoCA) score \<24, resulting in an inability to understand or complete the study questionnaires and assessments. 5. Use of growth hormone, estrogen, progesterone, testosterone, or related hormonal supplements within the previous 3 months, or presence of severe nutritional deficiency. 6. Participation in another clinical trial or a clinical trial involving traditional Chinese medicine supplements within the previous 3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Appendicular Skeletal Muscle Mass Index (ASMI) | Baseline, Week 12, Week 24, and 2 years after completion of the 24-week intervention | Appendicular skeletal muscle mass (ASM) is assessed using dual-energy X-ray absorptiometry (DXA). ASM is calculated as the sum of lean soft tissue mass of the arms and legs. Appendicular skeletal muscle mass index (ASMI) is calculated as ASM divided by height squared (kg/m²). Changes in ASMI from baseline are assessed at week 12, week 24, and 2 years after completion of the 24-week intervention.The primary efficacy endpoint is the change in ASMI from baseline to week 24. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Handgrip Strength | Baseline, Week 12, Week 24, and 2 years after completion of the 24-week intervention | Handgrip strength is measured using a handgrip dynamometer and reported in kilograms (kg), with higher values indicating greater muscle strength. |
| Change From Baseline in Five-Times Sit-to-Stand Test Performance | Baseline, Week 12, Week 24, and 2 years after completion of the 24-week intervention | Lower-extremity functional strength is assessed using the five-times sit-to-stand test. Completion time is recorded in seconds, with a shorter completion time indicating better performance. |
| Change From Baseline in Traditional Chinese Medicine Syndrome Score for Spleen Qi Deficiency | Baseline, Week 12, Week 24, and 2 years after completion of the 24-week intervention | Traditional Chinese medicine syndrome severity is assessed using the Spleen Qi Deficiency Syndrome Score. The scale evaluates predefined signs and symptoms associated with spleen qi deficiency syndrome, and a total syndrome score is calculated according to the prespecified scoring criteria. Higher scores indicate greater severity of spleen qi deficiency syndrome. |
| Change From Baseline in Gut Microbiota Composition | Baseline, Week 24, and 2 years after completion of the 24-week intervention | Gut microbiota composition is assessed using 16S rRNA gene sequencing of fecal samples. Changes in microbial community structure are evaluated using measures of microbial diversity and the relative abundance of bacterial taxa to characterize intervention-related alterations in the gut microbiota. |
| Change From Baseline in Cortical Hemodynamic Responses Assessed by Functional Near-Infrared Spectroscopy | Baseline, Week 24, and 2 years after completion of the 24-week intervention | Cortical hemodynamic responses are assessed using functional near-infrared spectroscopy (fNIRS) during motor-cognitive dual-task performance. Changes in cerebral oxygenation, including oxygenated hemoglobin responses in prefrontal and motor-related cortical regions, are evaluated to characterize intervention-related changes in cortical activation and brain functional responses. |
| Change From Baseline in Gait Speed | Baseline, Week 12, Week 24, and 2 years after completion of the 24-week intervention. | Gait speed is measured in meters per second (m/s), with higher values indicating better walking performance. |
| Change From Baseline in 6-Minute Walk Distance | Baseline, Week 12, Week 24, and 2 years after completion of the 24-week intervention. | Functional exercise capacity is assessed using the 6-minute walk test. The total distance walked is recorded in meters, with a longer distance indicating better exercise capacity. |
| Change From Baseline in Short Physical Performance Battery Score | Baseline, Week 12, Week 24, and 2 years after completion of the 24-week intervention. | Physical performance is assessed using the Short Physical Performance Battery (SPPB). The total score ranges from 0 to 12, with higher scores indicating better lower-extremity physical performance. |
| Change From Baseline in Timed Up and Go Test Completion Time | Baseline, Week 12, Week 24, and 2 years after completion of the 24-week intervention. | Mobility is assessed using the Timed Up and Go (TUG) test. Completion time is recorded in seconds, with a shorter completion time indicating better mobility. |
| Change From Baseline in Montreal Cognitive Assessment Score | Baseline, Week 12, Week 24, and 2 years after completion of the 24-week intervention. | Global cognitive function is assessed using the Montreal Cognitive Assessment (MoCA). The total score ranges from 0 to 30, with higher scores indicating better global cognitive function. |
| Change From Baseline in Stroop Color-Word Test Completion Time | Baseline, Week 12, Week 24, and 2 years after completion of the 24-week intervention. | Executive function and inhibitory control are assessed using the Stroop Color-Word Test. Completion time is recorded in seconds, with shorter completion time indicating better performance. |
| Change From Baseline in Stroop Color-Word Test Accuracy | Baseline, Week 12, Week 24, and 2 years after completion of the 24-week intervention. | Executive function and inhibitory control are assessed using the Stroop Color-Word Test. Accuracy is calculated as the percentage of correct responses, with higher percentages indicating better performance. |
| Change From Baseline in Relative Abundance of Metabolites Detected by Untargeted Metabolomics | Baseline, Week 24, and 2 years after completion of the 24-week intervention. | Untargeted metabolomics is performed on serum and fecal samples using liquid chromatography-mass spectrometry. Metabolite abundance is assessed semi-quantitatively based on LC-MS peak signals after XCMS preprocessing, internal-standard correction, and quality-control filtering. Changes from baseline are used to characterize intervention-related metabolic alterations. |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORZhizhen Liu
Fujian University of Traditional Chinese Medicine
Outcome results
None listed