Peiyuan Guben Tongluo Ointment for Elderly Sarcopenia

Overall Design: This study adopts a randomized, double-blind clinical trial design with both internal and external controls. Trial Flow: The trial consists of a screening/baseline period, a 12-week treatment administration period, and a 12-week follow-up period. The end-of-trial visit will be conducted at Week 24 after medication administration (EOS/EOT). Randomization and Blinding: Block randomization is applied in this study, with subjects randomized into each group at a 1:1 ratio under a double-blind design. Data Collection: Electronic Data Capture (EDC) system combined with patient diaries. External Control: External controls include published literature data and real-world study data.

• nutritional intervention (Dietary supplement): Provide protein and vitamin D supplementation.
• Exercise (Behavioral): Receive standardized Baduanjin training with unified movements; the training is conducted 3 times weekly, starting 3 hours after meals, with a duration of 30 minutes per session.
• Peiyuan Guben Tongluo Ointment (Ejiao concentrated) (Drug): Peiyuan Guben Tongluo Ointment (Ejiao concentrated): 20 g once daily, administered with warm water; Composition: Rehmanniae Radix Preparata 120 g, Rehmanniae Radix 120 g, Epimedii Folium 60 g, Achyranthis Bidentatae Radix 120 g, Eucommiae Cortex 60 g, Dipsaci Radix 90 g, Astragali Radix 150 g, Codonopsis Radix 150 g, Dioscoreae Rhizoma 150 g, Paeoniae Radix Alba (stir-fried) 120 g, Polygonati Odorati Rhizoma 100 g, Scrophulariae Radix 90 g, Ligustri Lucidi Fructus 100 g, Ecliptae Herba 100 g, Citri Reticulatae Pericarpium 90 g, Atractylodis Macrocephalae Rhizoma (stir-fried) 150 g, Aucklandiae Radix 30 g, Salviae Miltiorrhizae Radix et Rhizoma 120 g, Chuanxiong Rhizoma 60 g, Sedii Aizi Herba 120 g, Anemarrhenae Rhizoma 90 g; Excipients: Agarose 450 g, Xylitol 45 g. Excipients: Tortoise Shell Glue 150 g, Deer Horn Glue 150 g, Ejiao 150 g, Xylitol 45 g.
• Peiyuan Guben Tongluo Ointment (Agarose concentrated) (Drug): Peiyuan Guben Tongluo Ointment (Agarose concentrated): 20 g once daily, administered with warm water; Composition: Rehmanniae Radix Preparata 120 g, Rehmanniae Radix 120 g, Epimedii Folium 60 g, Achyranthis Bidentatae Radix 120 g, Eucommiae Cortex 60 g, Dipsaci Radix 90 g, Astragali Radix 150 g, Codonopsis Radix 150 g, Dioscoreae Rhizoma 150 g, Paeoniae Radix Alba (stir-fried) 120 g, Polygonati Odorati Rhizoma 100 g, Scrophulariae Radix 90 g, Ligustri Lucidi Fructus 100 g, Ecliptae Herba 100 g, Citri Reticulatae Pericarpium 90 g, Atractylodis Macrocephalae Rhizoma (stir-fried) 150 g, Aucklandiae Radix 30 g, Salviae Miltiorrhizae Radix et Rhizoma 120 g, Chuanxiong Rhizoma 60 g, Sedii Aizi Herba 120 g, Anemarrhenae Rhizoma 90 g; Excipients: Agarose 450 g, Xylitol 45 g.

Primary outcomes

• DXA-measured appendicular skeletal muscle mass [Baseline, week 12, week 24]: Detected by dual-energy X-ray absorptiometry (GE Healthcare, DXA). The skeletal muscle mass index (SMI) is defined as the ratio of DXA-measured skeletal muscle mass to the square of height.

Secondary outcomes

• Upper limb handgrip strength [Up to 24 weeks]: Use a hand dynamometer to record grip strength data for comparison.
• Handgrip strength [Baseline, week 12, week 24]: Use a hand dynamometer to record grip strength data for comparison.
• Timed Up and Go test (TUG) [Baseline, week 12, week 24]: Subjects shall sit on a chair with a seat height of 46 cm, a straight backrest and armrests (armrest height approximately 65 cm). They are required to stand up with minimal assistance from the armrests. The total time is recorded from leaving the backrest to standing upright, walking 3 meters at their usual walking speed, turning around, walking back, and sitting down fully against the chair back. The average value of three trials is calculated. Elderly individuals who routinely use walking aids may use them during the test.
• Berg Balance Scale (BBS) [Baseline, week 12, week 24]: The scale consists of 14 items in total, including sitting to standing, standing to sitting, standing unsupported, standing with eyes closed, reaching forward with outstretched arms, turning 360 degrees, alternating foot placement on a step, single-leg standing, etc. All items take 10-15 minutes to complete. Each item is scored from a minimum of 0 points to a maximum of 4 points, with a total possible score of 56 points. A higher score indicates better balance function; a score below 40 points suggests an increased risk of falls.
• TCM Syndrome Score [Baseline, week 12, week 24]: In accordance with the scoring criteria specified in the 《Guiding Principles for Clinical Research of New Traditional Chinese Medicine Drugs》, the total score for **Spleen-Kidney Deficiency Syndrome** was calculated.
• Peripheral blood white blood cell count [Baseline, week 12]: Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment. Hematology (Blood Routine): White Blood Cell count (WBC) Unit: ×10⁹/L (Number of white blood cells per liter of blood × 10⁹)
• Neutrophil count [Baseline, week 12]: Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment. Hematology (Blood Routine): Neutrophil percentage (NEUT%) Unit: % (Percentage of neutrophils among total white blood cells)
• Interleukin-2 [Baseline, week 12]: Measuring Interleukin-2 (IL-2) level, which is used to evaluate the activation of immune cells and the status of inflammatory response in the body.
• Interleukin-6 [Baseline, week 12]: Measuring Interleukin-6 (IL-6) level, which serves as an important indicator reflecting the degree of inflammation and stress response in the body.
• Mini Nutritional Assessment (MNA) [Baseline, week 12, week 24]: Nutritional status was evaluated using the Mini Nutritional Assessment (MNA). This scale comprehensively evaluates an individual's nutritional status through a series of questions covering body weight, dietary intake, mobility, mental state and other aspects. The full score of the scale is 30 points. Grading criteria: a total score ≥ 24 indicates good nutritional status; a score between 17 and 24 suggests risk of malnutrition; a total score below 17 confirms definite malnutrition.
• Activities of Daily Living (ADL) Scale [Baseline. week 12, week 24]: The Activities of Daily Living (ADL) scale, developed by American scholars Lawton and Brody in 1969, is a medical assessment tool composed of the Physical Self-Maintenance Scale (PSMS) and the Instrumental Activities of Daily Living (IADL). It is mainly used to evaluate subjects' functional levels in basic living skills such as feeding, dressing and mobility, as well as the ability to use instrumental tools. Constructed from two dimensions including PSMS and IADL, the scale contains a total of 10 assessment items.

Other outcomes

• Incidence, Severity, Timing, and Relationship of Adverse Events (AEs) [Baseline, week 12, week 24]: Adverse events will be evaluated in terms of type, incidence, severity, time of onset, and relationship to the study drug. Types of adverse events are classified as: Adverse Event (AE), Serious Adverse Event (SAE), and Suspected Unexpected Serious Adverse Reaction (SUSAR). Severity is graded as: mild, moderate, or severe. Mild: The subject can tolerate the event; it does not interfere with ongoing treatment, requires no special intervention, and has no impact on the subject's recovery. Moderate: The subject finds the event difficult to tolerate; it necessitates discontinuation of the study drug or special treatment, and it directly affects the subject's recovery. Severe: The event is life-threatening, results in death or permanent disability/incapacity, and requires immediate discontinuation of the study drug or emergency intervention.
• Alanine Aminotransferase [Baseline, week 12]: Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment. Alanine Aminotransferase (ALT) Unit: U/L (units per liter) All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory.
• γ-Glutamyl Transferase (γ-GT/GGT) [Baseline, week 12]: Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment. γ-Glutamyl Transferase (GGT) Unit: U/L (units per liter) All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory.
• Alkaline Phosphatase [Baseline, week 12]: Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment. Alkaline Phosphatase (ALP) Unit: U/L (units per liter) All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory.
• Aspartate Aminotransferase [Baseline, week 12]: Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment. Aspartate Aminotransferase (AST) Unit: U/L (units per liter) All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory.
• Total Bilirubin [Baseline, week 12]: Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment. Total Bilirubin (TBIL) Unit: μmol/L (micromoles per liter) All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory.
• Serum Creatinine [Baseline, week 12]: Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment. Serum Creatinine Unit: μmol/L (micromoles per liter) All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory.
• Blood Urea Nitrogen (BUN) [Baseline, week 12]: Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment. Blood Urea Nitrogen (BUN) Unit: mmol/L (millimoles per liter) All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory.
• Serum Uric Acid [Baseline, week 12]: Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment. Serum Uric Acid Unit: μmol/L (micromoles per liter) All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory.
• Serum Cystatin [Baseline, week 12]: Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment. Serum Cystatin Unit: mg/L All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory.
• Red Blood Cell count [Baseline, week 12]: Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment. Hematology (Blood Routine): Red Blood Cell count (RBC) Unit: ×10¹²/L (Number of red blood cells per liter of blood × 10¹²) All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory. Clinically significant abnormalities or changes are evaluated and reported as adverse events per protocol criteria.
• White Blood Cell count [Baseline, week 12]: Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment. White Blood Cell count (WBC) Unit: ×10⁹/L (Number of white blood cells per liter of blood × 10⁹) All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory.
• Hemoglobin [Baseline, week 12]: Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment. Hematology (Blood Routine): Hemoglobin (Hb)-Hemoglobin Concentration Unit: g/L (grams per liter) or g/dL All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory.
• Platelet count [Baseline, week 12]: Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment. Platelet count (PLT) Unit: ×10⁹/L (Number of platelets per liter of blood × 10⁹) All tests are conducted using standardized clinical laboratory methods at a certified central or local laboratory.
• Fasting Blood Glucose [Baseline, week 12]: Measuring Fasting Blood Glucose (FBG), which is the blood glucose level measured after fasting for 8 to 12 hours.
• Glycated Hemoglobin [Baseline, week 12]: Measuring Glycated Hemoglobin (HbA1c), which reflects the average blood glucose concentration over the past 2 to 3 months.
• Blood Lipids [Baseline, week 12]: Measuring fasting Total Cholesterol (TC), Low-Density Lipoprotein Cholesterol (LDL-C), High-Density Lipoprotein Cholesterol (HDL-C), and Triglycerides (TG).
• Incidence of Shanghuo Symptoms [Baseline, week12]: Record the occurrence of symptoms such as dry mouth, mouth and tongue ulcers, swollen and painful gums, excessive hunger with increased food intake, and constipation.
• Routine Stool Test [Baseline, week 12]: Microscopic and chemical examination of fecal specimens to evaluate fecal consistency and color, screen for red blood cells, white blood cells, parasite eggs, occult blood and other indicators, and identify intestinal inflammation, bleeding, infection and abnormal digestion and absorption. Unit of Measure: Qualitative results (-/+/++/+++), quantitative results (cells/HPF).
• Body Temperature [Baseline, week 12]: Body temperature (°C) is measured under standardized conditions (rest ≥5 minutes, using calibrated equipment) by trained study personnel.
• Pulse Rate [Baseline, week 12]: Pulse rate (beats per minute, bpm) is measured under standardized conditions (rest ≥5 minutes, using calibrated equipment) by trained study personnel.
• Respiratory Rate [Baseline, week 12]: Respiratory rate (breaths per minute) is measured under standardized conditions (rest ≥5 minutes, using calibrated equipment) by trained study personnel.
• Blood Pressure [Baseline, week 12]: Blood pressure (systolic and diastolic, mmHg) is measured under standardized conditions (rest ≥5 minutes, using calibrated equipment) by trained study personnel. Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) are recorded and reported separately.
• Pharmacokinetic (PK) Parameters-Plasma Maximum Observed Concentration (Cmax) [Baseline, week 12]: Plasma concentration measured from blood samples collected opportunistically at Week 4 (or Week 8/early discontinuation). Cmax is the maximum observed concentration post-dose. Parameters estimated using non-compartmental analysis or population PK modeling due to sparse sampling. Geometric mean and variability reported. Assessed as an exploratory pharmacokinetic biomarker. Unit of Measure: ng/mL (or appropriate unit, e.g., nmol/L)
• Pharmacokinetic (PK) Parameters-Time Curve (AUC0-last) [Baseline, week 12]: Area under the concentration-time curve from time zero to the last measurable concentration (AUC0-last) , estimated from sparse opportunistic sampling at Week 4 (or Week 8) using population PK methods. Geometric mean reported. Exploratory PK biomarker of exposure. Unit of Measure: h·ng/mL (or appropriate, e.g., h·nmol/L）
• Gut Microbial Alpha-diversity [Baseline, week 12]: Evaluation of microbial richness and evenness within fecal samples using 16S rRNA sequencing. Alpha-diversity represents the biological variety within a single sample. Unit of Measure: Shannon Diversity Index (a calculated score typically ranging from 0 to 5, where higher values indicate greater diversity).
• Gut Microbial Relative Abundance [Baseline, week 12]: Assessment of the taxonomic composition of the gut microbiota at the genus and species levels via metagenomic sequencing. Unit of Measure: Percentage of total sequences (%).
• Fecal Short-Chain Fatty Acid (SCFA) [Baseline, week 12]: Quantitative analysis of major SCFAs (acetate, propionate, and butyrate) using GC-MS. The sum of these concentrations will be reported. Unit of Measure: μ mol/g of feces.
• Fecal Metabolomic Profiles [Baseline, week 12]: Untargeted metabolomics analysis using LC-MS/GC-MS to identify global metabolic shifts and differential metabolites induced by the treatment. Unit of Measure: Normalized peak intensity (arbitrary units).

Sex: All, ages: 60 Years to 80 Years

Inclusion Criteria:

* Patients aged ≥ 60 years and ≤ 80 years, regardless of gender; ② Patients meeting the diagnostic criteria for sarcopenia in the elderly according to both traditional Chinese medicine (TCM) and Western medicine;

  * Patients meeting the TCM diagnostic criteria for Spleen-Kidney Deficiency Syndrome;

    * Able to take oral medications, willing to comply with the study intervention protocol, able to attend follow-up visits on time, and have signed the informed consent form.

Exclusion Criteria:

* Patients with quadriplegia, long-term bedridden status, zero muscle strength due to severe cerebrovascular accident, muscle atrophy caused by various factors, or inability to perform activities of daily living;

  * Patients with unclear consciousness, aphasia, delirium, inability to respond, or impaired time, location and orientation due to senile or vascular dementia;

    * Patients with severe mental illness, depressive state, or receiving relevant psychotropic medication; ④ Patients complicated with tumors, severe infections, gastrointestinal bleeding, hepatic and renal insufficiency, cardiac insufficiency, or other diseases affecting nutritional status; ⑤ Patients with hypersensitivity to the study drugs; patients who have received or are receiving traditional Chinese medicine treatment within the past 1 month; patients who have received medications affecting muscle contraction/relaxation within the past 1 month.

• Feng Hua Qian, Undergraduate, Principal investigator, Shanghai Yueyang Integrated Medicine Hospital