In recent years, the incidence rate and disability rate of osteoarthritis have continued to grow, and it has become a common chronic disease of elderly patients, second only to the "three highs", and poses a continuous threat to China's medical and health system and public health system. Knee osteoarthritis is the main type of osteoarthritis, ranking 11th in global disability diseases and 38th in disability adjusted life year loss, causing significant economic burden to patients, families, and society. At present, most of the treatment methods for KOA have limited efficacy, only relieving pain symptoms and cannot prevent cartilage damage and other tissue damage in the joints. Due to the limitations of adverse events, there is still no optimal treatment plan for KOA. Most studies believe that autologous mesenchymal stem cell transplantation is a new treatment method with good efficacy and good repair effect for mild to moderate cartilage defects. Given that there is currently no optimal treatment plan for KOA, human umbilical cord mesenchymal stem cell injection has potential development value and is of great significance for the treatment of KOA patients.
Osteoarthritis (OA) is a chronic inflammatory disease of the bone and joints, characterized by degenerative destruction of articular cartilage, subchondral bone sclerosis and osteophyte formation, and peripheral soft tissue inflammation and proliferation. Knee Osteoarthritis (KOA), which is negative and highly active, is the most common. Currently, there are approximately 1 billion KOA patients worldwide, with approximately 150 million patients in China, and the incidence rate increases with age. The clinical manifestation of KOA is repeated and prolonged bone and joint pain, which seriously affects the patient's quality of life, ultimately leading to joint structural damage and loss of function, causing a significant burden on individuals, families, and society. At present, there is a lack of effective treatment methods for KOA both domestically and internationally, and there is an urgent need to research new treatment strategies to meet clinical needs. Numerous studies have shown that local inflammation of the joint cavity and apoptosis of articular chondrocytes are the main pathological mechanisms of knee osteoarthritis. Therefore, the key to treating KOA is to inhibit the local inflammatory response of bone joints, promote chondrocyte regeneration, repair damaged joint surfaces, and restore their normal structure and function. Mesenchymal Stem Cells (MSCs) are the most widely studied pluripotent stem cells. It exists in various tissues, has multidirectional differentiation potential, homing effect and powerful paracrine function, can regulate tissue microenvironment, promote damaged tissue repair through cell replacement, promote in-situ cell regeneration, anti-inflammatory and immune regulation and other mechanisms. Therefore, mesenchymal stem cell therapy has become the focus of KOA new therapy research. A large number of studies have shown that MSCs can be induced to differentiate into stable mature chondrocytes that can express proteoglycan and type II collagen. Fluorescently labeled MSCs could still be detected 10 weeks after injection into the joint cavity of osteoarthritis model animals, suggesting that MSCs homed in the injured articular cartilage tissue and participated in the regeneration and repair of the injured tissue. The effectiveness of MSCs therapy for KOA has been demonstrated in osteoarthritis models in different animals including rats, rabbits, sheep, pigs, and monkeys. MSCs from different sources can effectively inhibit the inflammatory response and chondrocyte injury in model animals, and stimulate the regeneration and repair of injured chondrocytes. Based on the Phase I clinical trial that has entered the follow-up phase, the applicant is applying for a "Multi-center, randomized, double-blinded, placebo-controlled Phase II Clinical Trial of UC-MSCs for the Treatment of Knee Osteoarthritis". A total of 100 subjects are planned to be enrolled and randomly assigned in a 2:2:1 ratio to Treatment Group 1 (5.0 × 10⁶ cells/2.5 mL, 40 subjects), Treatment Group 2 (2.0 × 10⁷ cells/2.5 mL, 40 subjects) and Placebo group (20 subjects). The objective is to obtain a more comprehensive and direct assessment of the safety, efficacy, and optimal effective dose of UC-MSCs for knee osteoarthritis.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
100
1 time of UC-MSCs (5×10\^6 UC-MSCs/2.5mL, single injection into the knee cavity
1 time of UC-MSCs (2×10\^7 UC-MSCs/2.5mL, single injection into the knee cavity).
1 time of placebo (2.5mL normal saline containing 1 % human serum albumin, single injection into the knee cavity)
Guangzhou First People's Hospital
Wuhan, China
RECRUITINGWuhan Fourth Hospital
Wuhan, China
RECRUITINGWuhan Third Hospital
Wuhan, China
RECRUITINGChanges in WOMAC score from baseline
Time frame: From Baseline (0 Week) to post-dose, 4 weeks, 12 weeks, 24 weeks, and 48 weeks after treatment
Changes in VAS score from baseline
Time frame: From Baseline (0 Week) to post-dose, 4 weeks, 12 weeks, 24 weeks, and 48 weeks after treatment]
Changes in knee joint range of motion from baseline
knee joint range of motion
Time frame: From Baseline (0 Week) to 4 weeks, 12 weeks, 24 weeks, 48 weeks after treatment
Changes in X-Kellgren-Lawrence grading
Time frame: From Baseline (0 Week) to 24 weeks, 48 weeks after treatment
Changes of MRI-Roberts cartilage repair score compared with baseline
Time frame: From Baseline (0 Week) to 24 weeks, 48 weeks after treatment
minimum joint space width (mJSW) from baseline
Time frame: From Baseline (0 Week) to 24 weeks, 48 weeks after treatment
Changes of cartilage thickness compared with baseline
Time frame: From Baseline (0 Week) to 24 weeks, 48 weeks after treatment
Changes of synovial inflammation score (reference MOAKS) compared with baseline
Time frame: From Baseline (0 Week) to 24 weeks, 48 weeks after treatment
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