Knee Osteoarthritis
Conditions
Keywords
Knee Osteoarthritis, Qi and Blood Deficiency Pattern, Knee Pain Ejiao Paste
Brief summary
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.
Detailed description
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.
Interventions
DRUGKnee Pain Ejiao Paste
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.
DRUGKnee Pain Ejiao-free Clear Paste
Using an Ejiao-free clear paste as a parallel control.
Sponsors
ShuGuang Hospital
Shanghai University of Traditional Chinese Medicine
DongE E Jiao Coporation Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Meets the diagnostic criteria for knee osteoarthritis (OA), with unilateral or bilateral knee involvement 2. Prior to randomization, the NRS pain score of the target knee joint ≥4, and the NRS score of the contralateral knee joint is not higher than that of the target knee joint; among the 5 pain items on the WOMAC, at least 1 item scores ≥40 mm 3. Body Mass Index (BMI) ≤32 kg/m² 4. Meets the diagnostic criteria for Qi and Blood Deficiency Pattern 5. Age between 40 and 75 years inclusive (40 years ≤ age ≤ 75 years), male or female 6. The Kellgren-Lawrence grading of the target knee joint is grade I-III, and the Kellgren-Lawrence grading of the contralateral knee joint is not higher than that of the target knee joint (in cases of unilateral disease, the affected side is the target knee joint; in cases of bilateral disease, the target knee joint must satisfy the above criteria) 7. Voluntarily participates in this clinical trial, provides informed consent, and signs the informed consent form
Exclusion criteria
1. Other conditions exist that may confound the assessment of function and pain in the target knee joint, such as: systemic diseases that may involve the joints (e.g., gouty arthritis, rheumatoid arthritis, etc.), chronic inflammatory or connective tissue diseases, neurological disorders, Paget's disease involving the knee, localized pain resulting from radicular lumbar compression, and any other conditions that may interfere with the efficacy assessment 2. Use of other Chinese or Western medicines or therapies for osteoarthritis within one week prior to screening (excluding celecoxib tablets): such as non-steroidal anti-inflammatory drugs (excluding aspirin at no more than 325mg daily for cardiovascular disease prevention) , analgesics (including opioids, non-steroidal anti-inflammatory drugs, cyclooxygenase-2 (COX-2) inhibitors, tramadol, ketamine, clonidine, gabapentin, pregabalin and/or cannabinoids), or traditional Chinese medicine formulations with similar therapeutic indications to Knee Pain Ejiao Paste (i.e., those possessing qi-tonifying and blood-nourishing effects) 3. Use within 4 weeks prior to screening of drugs that relieve osteoarthritis (OA) symptoms (such as glucosamine, chondroitin sulfate, diacerein, etc.), any nutritional supplements with potential activity on articular cartilage, systemic corticosteroids or immunosuppressive drugs (subjects requiring only inhaled corticosteroids for asthma treatment may be enrolled) 4. Receipt of biological products or intra-articular drug injection therapy (e.g., glucocorticoids, sodium hyaluronate, medical chitosan, growth factors, platelet-rich plasma, stem cell therapy, etc.) within 3 months prior to screening 5. Invasive procedures such as arthroscopy or lavage of the target knee joint within 6 months before screening or planned during the study period 6. Previous or planned target knee joint replacement (partial or total), autologous osteochondral mosaicplasty, microfracture, meniscectomy, osteotomy or other surgery during the study period 7. Planned change or new use of mobility aids (e.g., wheelchair, walker, cane or crutch) or need for lower limb prosthesis and/or structural knee brace during the study period 8. Investigator-judged serious comorbid cardiovascular, cerebrovascular, gastrointestinal diseases, poorly controlled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg), or other conditions that could affect the assessment of the investigational product's efficacy and safety 9. Laboratory abnormalities: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>1.5 times the upper limit of normal (ULN), or creatinine (Cr) \>ULN 10. Known or suspected allergy to the investigational product, rescue medication, or any of their components 11. Pregnant or lactating women, or women of childbearing potential planning pregnancy from enrollment through 3 months after the end of the study 12. Known or suspected history of alcohol or drug abuse 13. Intellectual disability, psychosis, or neurosis 14. Subjects who participated in any interventional drug clinical trial and received the investigational drug within 3 months prior to enrollment, or who are within 5 half-lives (whichever is longer) of any other clinical trial drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in Numerical Rating Scale (NRS) score for target knee pain at Week 12 | Screening Period/Baseline, 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Electronic Diary (ePRO) Joint Pain NRS Score | Baseline to Week 12 | During the treatment period, subjects will complete the NRS score for target knee pain and other records on ePRO daily. |
| Change from baseline in NRS score for target knee pain at Weeks 4 and 8 | Screening Period/Baseline, Week 4, and Week 8 | 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. |
| Pain relief rate of target knee pain at Weeks 4, 8, and 12 post-treatment | Screening Period/Baseline, Week 4, Week 8, and Week 12 | 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%. |
| Time to onset of target knee pain relief | Baseline to Week 12 | Time (in days) to the first ≥ 25% reduction from baseline in target knee pain NRS score (as recorded in the diary card). |
| Change from baseline in WOMAC total score for the target knee at Weeks 4, 8, and 12 post-treatment | Screening Period/Baseline, Week 4, Week 8, and Week 12 | Comparison of the change from baseline in WOMAC total score between groups at Weeks 4, 8, and 12 post-treatment. |
| Changes from baseline in WOMAC subscale scores (Pain, Stiffness, and Physical Function) for the target knee at Weeks 4, 8, and 12 post-treatment | Screening Period/Baseline, Week 4, Week 8, and Week 12 | 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. |
| Comparison of MOAKS scores for joint effusion in the target knee at Week 12 post-treatment | Screening Period/Baseline, Week 12 | Comparison of the change from baseline in MOAKS joint effusion scores between groups at Week 12 post-treatment. |
| Change from baseline in subject satisfaction scores at Week 12 post-treatment | Screening Period/Baseline, Week 4, Week 8, and Week 12 | 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. |
| Change from baseline in investigator satisfaction scores at Week 12 post-treatment | Screening Period/Baseline, Week 4, Week 8, and Week 12 | 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. |
| Consumption of rescue medication during the treatment period | Baseline to Week 12 | Comparison of the consumption of Celecoxib tablets as rescue medication between groups during the study period. |
| Effective rate of TCM syndrome at Weeks 4, 8, and 12 post-treatment | Screening Period/Baseline, Week 4, Week 8, and Week 12 | 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%. |
| Changes from baseline in TCM syndrome total scores and individual symptom scores at Weeks 4, 8, and 12 post-treatment | Screening Period/Baseline, Week 4, Week 8, and Week 12 | 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. |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORYuelong Cao, Ph.D
Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine
Outcome results
None listed