Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Shanghai University of Traditional Chinese Medicine | OTHER |
| DongE E Jiao Coporation Limited | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
To explore the analgesic efficacy of Knee Pain Ejiao Paste in the treatment of knee osteoarthritis (Qi and Blood Deficiency Pattern) after 12 weeks, using an Ejiao-free clear paste as a parallel control and incorporating a synthetic external control.
Overall Design: This study employs a randomized, double-blind, internal and external dual-control clinical trial design. Trial Procedures: The trial consists of a screening/baseline period and a 12-week treatment period, with an End-of-Study (EOS) or End-of-Treatment (EOT) visit conducted after 12 weeks of administration. Randomization and Blinding: A stratified block randomization method will be used to assign participants to each group in a 1:1 ratio, with competitive enrollment across all centers and a double-blind design. External Control: Literature-based data. Data Collection: Electronic Data Capture (EDC) system and Electronic Patient-Reported Outcome (ePRO) system.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Knee Pain Ejiao Paste | Experimental | Knee Pain Ejiao Paste: Oral administration, 1 bag per dose, twice daily (20g per dose); Composition: Xi Yang Shen (Panacis Quinquefolii Radix, 260g), Long Yan Rou (Arillus Longan, 1300g), Shan Yao (Dioscoreae Rhizoma, 1300g), and E Jiao (Colla Corii Asini, 350g); Instruction: It is recommended to take the medication at a fixed time each day. |
|
| Knee Pain Ejiao-free Clear Paste | Placebo Comparator | Knee Pain Ejiao-free Clear Paste: Oral administration, 1 bag per dose, twice daily (20g per dose); Composition: Xi Yang Shen (Panacis Quinquefolii Radix, 260g), Long Yan Rou (Arillus Longan, 1300g), Shan Yao (Dioscoreae Rhizoma, 1300g), and Mu Tang Chun (Xylitol, 350g) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Knee Pain Ejiao Paste | Drug | By comparing Knee Pain Ejiao Paste with the base formula, Knee Pain Ejiao-free Clear Paste, this study minimizes confounding factors such as dosage form, administration method, and matrix components. This approach allows for a precise evaluation of the incremental therapeutic benefits contributed by the addition of Ejiao, thereby providing direct evidence for the medicinal value of Colla Corii Asini. |
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline in Numerical Rating Scale (NRS) score for target knee pain at Week 12 | Selection of the target knee joint: For participants with unilateral involvement, the affected knee is designated as the target knee. In cases of bilateral involvement, the knee with the higher Numerical Rating Scale (NRS) pain score will be selected as the target knee. If the pain NRS scores are identical for both knees, the right knee joint will be chosen as the target knee. | Screening Period/Baseline, Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Patient Electronic Diary (ePRO) Joint Pain NRS Score | During the treatment period, subjects will complete the NRS score for target knee pain and other records on ePRO daily. | Baseline to Week 12 |
| Change from baseline in NRS score for target knee pain at Weeks 4 and 8 |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse Event (AE) | Adverse events will be evaluated and recorded based on their type, incidence, severity, timing, and causality (relationship to the study drug). | Week 4, Week 8, and Week 12 |
| Vital Signs (Body Temperature) |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Yuelong Cao, Ph.D | Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine | Shanghai | Shanghai Municipality | 201203 | China | ||
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D020370 | Osteoarthritis, Knee |
| ID | Term |
|---|---|
| D010003 | Osteoarthritis |
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Knee Pain Ejiao-free Clear Paste | Drug | Using an Ejiao-free clear paste as a parallel control. |
|
Selection of the target knee joint: For participants with unilateral involvement, the affected knee is designated as the target knee. In cases of bilateral involvement, the knee with the higher Numerical Rating Scale (NRS) pain score will be selected as the target knee. If the pain NRS scores are identical for both knees, the right knee joint will be chosen as the target knee. |
| Screening Period/Baseline, Week 4, and Week 8 |
| Pain relief rate of target knee pain at Weeks 4, 8, and 12 post-treatment | Effectiveness is defined as a ≥ 50% decrease in the target knee pain NRS score relative to baseline, where the reduction rate = [(Pre-trearment score - Post-treatment score) ÷ Pre-trearment score] × 100%. | Screening Period/Baseline, Week 4, Week 8, and Week 12 |
| Time to onset of target knee pain relief | Time (in days) to the first ≥ 25% reduction from baseline in target knee pain NRS score (as recorded in the diary card). | Baseline to Week 12 |
| Change from baseline in WOMAC total score for the target knee at Weeks 4, 8, and 12 post-treatment | Comparison of the change from baseline in WOMAC total score between groups at Weeks 4, 8, and 12 post-treatment. | Screening Period/Baseline, Week 4, Week 8, and Week 12 |
| Changes from baseline in WOMAC subscale scores (Pain, Stiffness, and Physical Function) for the target knee at Weeks 4, 8, and 12 post-treatment | Comparison of the change from baseline in WOMAC subscale scores (Pain, Stiffness, and Physical Function) between groups at Weeks 4, 8, and 12 post-treatment. | Screening Period/Baseline, Week 4, Week 8, and Week 12 |
| Comparison of MOAKS scores for joint effusion in the target knee at Week 12 post-treatment | Comparison of the change from baseline in MOAKS joint effusion scores between groups at Week 12 post-treatment. | Screening Period/Baseline, Week 12 |
| Change from baseline in subject satisfaction scores at Week 12 post-treatment | Comparison of the change from baseline in subject satisfaction scores between groups at Weeks 4, 8, and 12, as well as the proportion of satisfied subjects between groups. | Screening Period/Baseline, Week 4, Week 8, and Week 12 |
| Change from baseline in investigator satisfaction scores at Week 12 post-treatment | Comparison of the change from baseline in investigator satisfaction scores between groups at Weeks 4, 8, and 12 post-treatment, as well as the proportion of investigator-rated satisfaction between groups. | Screening Period/Baseline, Week 4, Week 8, and Week 12 |
| Consumption of rescue medication during the treatment period | Comparison of the consumption of Celecoxib tablets as rescue medication between groups during the study period. | Baseline to Week 12 |
| Effective rate of TCM syndrome at Weeks 4, 8, and 12 post-treatment | Comparison of the between-group differences in the effective rate at Weeks 4, 8, and 12 post-treatment. Based on the results of the TCM Syndrome Quantitative Rating Scale, TCM syndrome scores are calculated before and after treatment, and the efficacy is evaluated according to the following criteria: Effective: A reduction in TCM syndrome score of ≥ 50% Ineffective: A reduction in TCM syndrome score of less than 50% The reduction rate of TCM syndrome score is caculated as: Reduction Rate = [(Pre-trearment score - Post-treatment score) ÷ Pre-trearment score] × 100%. | Screening Period/Baseline, Week 4, Week 8, and Week 12 |
| Changes from baseline in TCM syndrome total scores and individual symptom scores at Weeks 4, 8, and 12 post-treatment | Comparison of the change from baseline in TCM syndrome total scores and individual symptom scores between groups at Weeks 4, 8, and 12 post-treatment. | Screening Period/Baseline, Week 4, Week 8, and Week 12 |
Body temperature (°C) is measured under standardized conditions (rest ≥5 minutes, using calibrated equipment) by trained study personnel.
| Screening Period/Baseline, Week 4, Week 8, and Week 12 |
| Vital Signs (Pulse Rate) | Pulse rate (beats per minute, bpm) is measured under standardized conditions (rest ≥5 minutes, using calibrated equipment) by trained study personnel. | Screening Period/Baseline, Week 4, Week 8, and Week 12 |
| Vital Signs (Respiratory Rate) | Respiratory rate (breaths per minute) is measured under standardized conditions (rest ≥5 minutes, using calibrated equipment) by trained study personnel. | Screening Period/Baseline, Week 4, Week 8, and Week 12 |
| Vital Signs (Blood Pressure) | 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. | Screening Period/Baseline, Week 4, Week 8, and Week 12 |
| Laboratory Parameters (Hematology-Red Blood Cell count) | 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) | Screening Period/Baseline, Week 12 |
| Laboratory Parameters (Hematology-White Blood Cell count) | 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) | Screening Period/Baseline, Week 12 |
| Laboratory Parameters (Hematology- Platelet count) | 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): Platelet count (PLT) Unit: ×10⁹/L (Number of platelets per liter of blood × 10⁹) | Screening Period/Baseline, Week 12 |
| Laboratory Parameters (Hematology-Hemoglobin ) | 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 (HGB)-Hemoglobin Concentration Unit: g/L (grams per liter) or g/dL | Screening Period/Baseline, Week 12 |
| Laboratory Parameters (Hematology-Neutrophil percentage ) | 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) | Screening Period/Baseline, Week 12 |
| Laboratory Parameters (Liver Function-Alanine Aminotransferase) | Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment. Liver Function: Alanine Aminotransferase (ALT) Unit: U/L (units per liter) | Screening Period/Baseline, Week 12 |
| Laboratory Parameters (Liver Function- Aspartate Aminotransferase) | Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment. Liver Function: Aspartate Aminotransferase (AST) Unit: U/L (units per liter) | Screening Period/Baseline, Week 12 |
| Laboratory Parameters (Liver Function-Total Bilirubin) | Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment. Liver Function: Total Bilirubin (TBIL) Unit: μmol/L (micromoles per liter) | Screening Period/Baseline, Week 12 |
| Laboratory Parameters (Liver Function-Alkaline Phosphatase) | Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment. Liver Function:Alkaline Phosphatase (ALP) Unit: U/L (units per liter) | Screening Period/Baseline, Week 12 |
| Laboratory Parameters (Liver Function-γ-Glutamyl Transferase) | Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment. Liver Function: γ-Glutamyl Transferase (GGT) Unit: U/L (units per liter) | Screening Period/Baseline, Week 12 |
| Laboratory Parameters (Renal Function- Serum Creatinine ) | Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment. Renal Function: Serum Creatinine (Scr) Unit: μmol/L (micromoles per liter) or mg/dL | Screening Period/Baseline, Week 12 |
| Laboratory Parameters (Renal Function- Blood Urea Nitrogen) | Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment. Renal Function: Blood Urea Nitrogen (BUN) / Urea Unit: mmol/L (millimoles per liter) or mg/dL | Screening Period/Baseline, Week 12 |
| Laboratory Parameters (Renal Function- Estimated Glomerular Filtration Rate) | Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment. Renal Function: Estimated Glomerular Filtration Rate (eGFR) Unit: mL/min/1.73m² (milliliters per minute per 1.73 square meters) | Screening Period/Baseline, Week 12 |
| Laboratory Parameters (Renal Function- Urine Albumin-Creatinine Ratio) | Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment. Renal Function: Urine Albumin-Creatinine Ratio (UACR) Unit: mg/g (milligrams per gram) or mg/mmol | Screening Period/Baseline, Week 12 |
| Laboratory Parameters (Urinalysis-Protein ) | Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment. Urinalysis (Urine Routine): Protein (PRO) Unit: Qualitative/Semi-quantitative, typically reported as: Negative (-), Trace (±), +, ++, +++, ++++ (or mg/dL, g/L) | Screening Period/Baseline, Week 12 |
| Laboratory Parameters (Urinalysis-Glucose ) | Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment. Urinalysis (Urine Routine): Glucose (GLU) Unit: Qualitative/Semi-quantitative, typically reported as: Negative (-), Trace (±), +, ++, +++, ++++ (or mmol/L, mg/dL) | Screening Period/Baseline, Week 12 |
| Laboratory Parameters (Urinalysis-Red Blood Cells) | Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment. Urinalysis (Urine Sediment Microscopy): Red Blood Cells (RBC) Unit: per high-power field (/HPF) or per microliter (μL) (microscope count) | Screening Period/Baseline, Week 12 |
| Laboratory Parameters (Urinalysis-Leukocytes) | Laboratory tests are performed as part of routine safety monitoring to evaluate potential hematological, hepatic, renal, or urinary effects of the investigational treatment. Urinalysis (Urine Routine): Leukocytes (LEU) Unit: per high-power field (/HPF) or per microliter (μL) (microscope count) | Screening Period/Baseline, Week 12 |
| Blood Glucose | Measuring Fasting Blood Glucose (FBG), which is the blood glucose level measured after fasting for 8 to 12 hours. | Screening Period/Baseline, Week 12 |
| Blood Lipids | Measuring fasting Total Cholesterol (TC), Low-Density Lipoprotein Cholesterol (LDL-C), High-Density Lipoprotein Cholesterol (HDL-C), and Triglycerides (TG). | Screening Period/Baseline, Week 12 |
| Heart Rate on 12-lead electrocardiogram | Heart rate (beats per minute) is measured from a standard 12-lead electrocardiogram recorded after at least 5 minutes of rest in a supine position, using calibrated equipment. Measurements are performed by trained personnel and interpreted by qualified investigators or cardiologists. Unit of Measure: beats per minute (bpm) | Screening Period/Baseline, Week 12 |
| PR Interval on 12-lead electrocardiogram | PR interval (milliseconds) is measured from a standard 12-lead electrocardiogram recorded after at least 5 minutes of rest in a supine position, using calibrated equipment. Measurements are performed by trained personnel and interpreted by qualified investigators or cardiologists. Unit of Measure: milliseconds (ms) | Screening Period/Baseline, Week 12 |
| QRS Duration on 12-lead electrocardiogram | QRS duration (milliseconds) is measured from a standard 12-lead electrocardiogram recorded after at least 5 minutes of rest in a supine position, using calibrated equipment. Measurements are performed by trained personnel and interpreted by qualified investigators or cardiologists. Monitored for potential ventricular conduction abnormalities. Unit of Measure: milliseconds (ms) | Screening Period/Baseline, Week 12 |
| QT Interval on 12-lead electrocardiogram | QT interval (milliseconds) is measured from a standard 12-lead electrocardiogram recorded after at least 5 minutes of rest in a supine position, using calibrated equipment. Measurements are performed by trained personnel and interpreted by qualified investigators or cardiologists. Unit of Measure: milliseconds (ms) | Screening Period/Baseline, Week 12 |
| Corrected QT Interval (QTc) on 12-lead electrocardiogram | Corrected QT interval (QTc, milliseconds) is calculated from the QT interval on a standard 12-lead electrocardiogram (recorded after ≥5 minutes rest, supine position, calibrated equipment) using Bazett or Fridericia formula as specified in the protocol. Interpreted by qualified cardiologists or trained investigators. Unit of Measure: milliseconds (ms) | Screening Period/Baseline, Week 12 |
| Pharmacokinetic (PK) Parameters-Plasma Maximum Observed Concentration (Cmax) | Plasma concentration measured from blood samples collected at Baseline, Weeks 4, 8, and 12( or early out of study).The exact time of blood collection and the time of the dose most recent to the collection must be recorded for each visit. 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) | Screening Period/Baseline, Week 4, Week 8, and Week 12 |
| Pharmacokinetic (PK) Parameters-Plasma Trough Concentration (Ctrough) | Plasma concentration measured from blood samples collected at Baseline, Weeks 4, 8, and 12( or early out of study).The exact time of blood collection and the time of the dose most recent to the collection must be recorded for each visit. Ctrough is the observed minimum concentration at the end of the dosing interval. Reported as geometric mean and variability. Exploratory pharmacokinetic endpoint focusing on steady-state trough exposure. Unit of Measure: ng/mL (or nmol/L, adjust based on drug) | Screening Period/Baseline, Week 4, Week 8, and Week 12 |
| Pharmacokinetic (PK) Parameters-Time Curve (AUC0-last) | Area under the concentration-time curve from time zero to the last measurable concentration (AUC0-last), estimated 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) | Screening Period/Baseline, Week 4, Week 8, and Week 12 |
| Gut Microbial Alpha-diversity | 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). | Screening Period/Baseline, Week 12 |
| Gut Microbial Relative Abundance | 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 (%). | Screening Period/Baseline, Week 12 |
| Fecal Metabolomic Profiles | 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). | Screening Period/Baseline, Week 12 |
| Fecal Short-Chain Fatty Acid (SCFA) | 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. | Screening Period/Baseline, Week 12 |
| Plasma Concentration of Cartilage Oligomeric Matrix Protein (COMP) | Evaluation of cartilage turnover and degradation levels. COMP is a key structural protein of the cartilage matrix, and its plasma concentration reflects the rate of cartilage breakdown in patients with knee osteoarthritis. Measured using Enzyme-Linked Immunosorbent Assay (ELISA). Unit of Measure: ng/mL | Screening Period/Baseline, Week 4, Week 8, and Week 12 |
| Plasma Level of C-Terminal Cross-Linked Telopeptide of Type II Collagen (CTX-II) | Assessment of cartilage collagen degradation. CTX-II is a specific biomarker for the degradation of type II collagen, the primary collagen found in articular cartilage. Higher levels are associated with increased radiographic progression of knee osteoarthritis. Measured using high-sensitivity immunoassay. Unit of Measure: pg/mL | Screening Period/Baseline, Week 4, Week 8, and Week 12 |
| Plasma Concentration of Tryptophan | Assessment of systemic amino acid metabolism and inflammatory signaling. Tryptophan is an essential amino acid whose metabolic pathways (such as the kynurenine pathway) are often altered by chronic inflammation in knee osteoarthritis. Changes in tryptophan levels can reflect the metabolic impact of treatment on systemic inflammation and pain-related pathways. Measured using Liquid Chromatography-Mass Spectrometry (LC-MS). Unit of Measure: nmol/L | Screening Period/Baseline, Week 4, Week 8, and Week 12 |
| Shanghai Municipal Hospital of Traditional Chinese Medicine |
| Shanghai |
| Shanghai Municipality |
| 201801 |
| China |
| D012216 |
| Rheumatic Diseases |