Knee Osteoarthritis
Conditions
Keywords
Knee, Osteoarthritis, Peripheral blood mononuclear cells
Brief summary
The goal of this Phase II/III, double-blinded, multicenter clinical trial is to assess the clinical efficacy of autologous peripheral blood mononuclear cells (PBMCs) in the management of knee osteoarthritis (KOA). The main questions it aims to answer are: 1. To determine the safety of the PCP-PBMCs injection 2. To compare the long-term efficacy between PCP-PBMCs and methylprednisolone on pain relief and motor function restoration 3. To analyze improving quality of life after the PCP-PBMCs treatment.
Detailed description
240 patients from both genders diagnosed with knee osteoarthritis, will be enrolled according to inclusion and exclusion criteria. These patients will be randomly injected with 100-200 million PBMCs, 20-60 million PBMCs or methylpredinisolone. They are then followed by clinical assessment, laboratory investigations as well as X-ray imaging of the injected knee.
Interventions
BIOLOGICALHigh-dose PCP-PBMCs injection
4 mL 100-200 million PCP-PBMCs injection into synovial cavity
DRUGSolu-Medrol
4 mL solu-medrol solution, injected into synovial cavity
BIOLOGICALLow-dose PCP-PBMCs injection
4 mL 20-60 million PCP-PBMCs injection into synovial cavity
Sponsors
DuoGenic StemCells Corporation (DGSC)
National Taiwan University Hospital
National Cheng-Kung University Hospital
Chang Gung Memorial Hospital, Chiayi
Kaoshiung Chang Gung Memorial Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Tibiofemoral osteophytes on x-ray (Kellgren-Lawrence grade of 2-4) * Age ≥ 40 and ≤ 80 years. * Moderate to severe knee pain * Reduced joint space width at the medial part of the knee compared to the lateral part under x-ray examination. If standing is not feasible, the same supine position must be used consistently for follow-up. * A minimal pain score of 5 measured by both NRS and VAS when walking last week. * Knee pain on most days (no less than 15 days) in the 4 weeks before screening * Patients have experienced that NSAID or opioid pain medication failed to control knee pain in the last year. * Patients have experienced that a single intra-articular injection of medicines, such as steroids, hyaluronic acid, or platelet-rich plasma, failed to control the knee pain over 6 months. * Non-invasive treatments did not control the knee pain. Conservative and non-invasive treatment regimens may include any or all of the following: initial rest, muscle relaxants, massage, and oral medications, e.g., anti-inflammatory drugs, analgesics, narcotics/opioids. * The patients have taken supervised physical and rehabilitation therapy, such as daily walking routines, therapeutic exercises, sonication, heat/cold therapy, and electric stimulation for knee pain control within the last year.
Exclusion criteria
* Patients who have taken knee, distal femur, or proximal tibia surgery. * Patients who took an intra-articular injection of medicine, such as steroids, hyaluronic acid, or platelet-rich plasma, in the last 3 months. * Reduced joint space width at the lateral part of the knee compared to the medial part under x-ray examination. * Patients who have severe varus deformity and tibiofemoral alignments are larger than 20 degrees. * Patients who cannot cooperate with the two-year follow-up. * Patients who have had tumor, infection, or trauma at the time of recruitment. * Patients with abnormal blood routine test, such as severe anemia, leukemia, sepsis, platelet dysfunction, or other blood-related diseases. * Patients who cannot agree to the withdrawal of non-steroid anti-inflammatory drugs (NSAIDs) or opioids during the trial period. * Patients who cannot cooperate with blood drawing. * The body mass index (BMI) value of the patient is higher than 30. * Female subjects who are pregnant, breastfeeding, planning to become pregnant, or unable to cooperate in contraception during the trial. * Subjects with a history of neurocognitive disorders, or those who have sought neurological consultation due to suspected dementia or memory decline * History of post-traumatic osteoarthritis. * History of rheumatoid arthritis, gouty arthritis, spontaneous osteonecrosis of the knee (SONK), or hemophilia. * Employees or family members of the PI and co-PI.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Reduction in Numeric Rating Scale (NRS) Score | Up to 52 weeks | Mean reduction in NRS for OA pain from baseline to post-treatment. NRS is a 11-point scale ranging from 0 (no pain) to 10 (worst pain imaginable) with a minimal clinically important difference (MCID) of 2.0. Participants are required to indicate a score on the scale that corresponds to their perceived level of pain in their knees. |
| Changes in scores on the Knee injury and Osteoarthritis Outcome Score (KOOS) | Up to 52 weeks | The KOOS evaluates symptoms and function in subjects with knee OA, holding five separately scored subscales: Pain, other Symptoms, Function in daily living (ADL), Function in Sport and Recreation (Sport/Rec), and knee-related Quality of Life (QOL). The KOOS ranges from 0 to 100, with lower scores indicating worse pain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Reduction in Numeric Rating Scale (NRS) Score | Up to 104 weeks | Mean reduction in NRS for OA pain from baseline to post-treatment. NRS is a 11-point scale ranging from 0 (no pain) to 10 (worst pain imaginable) with a minimal clinically important difference (MCID) of 2.0. Participants are required to indicate a score on the scale that corresponds to their perceived level of pain in their knees. |
| Changes in scores on the Knee injury and Osteoarthritis Outcome Score (KOOS) | Up to 104 weeks | The KOOS evaluates symptoms and function in subjects with knee OA, holding five separately scored subscales: Pain, other Symptoms, Function in daily living (ADL), Function in Sport and Recreation (Sport/Rec), and knee-related Quality of Life (QOL). The KOOS ranges from 0 to 100, with lower scores indicating worse pain. |
| Mean Reduction in the Visual Analog Scale (VAS) | Up to 104 weeks | Mean reduction in VAS for osteoarthritis (OA) knee pain from baseline to post-treatment. VAS is a 10-centimeter continuous scale ranging from 0 (no pain) to 10 (worst imaginable pain). Participants are instructed to mark a point along the line that best represents the intensity of their perceived knee pain. The distance in centimeters from the "no pain" anchor point is measured to quantify pain severity. Changes in VAS scores are used to assess treatment efficacy over time. |
| Changes in scores on the Intermittent and Constant Osteoarthritis Pain (ICOAP) questionnaire | Up to 104 weeks | The ICOAP is an 11-item measure that assesses pain in individuals with knee OA, taking into account both constant and intermittent pain experiences. The ICOAP is a 5-point Likert scale, ranging from 0 to 100, with higher scores indicating worse pain. |
| Changes in scores on the Assessment of Quality of Life 8 Dimension (AQoL-8D) | Up to 104 weeks | AQoL-8D consists of eight domains (independent living, happiness, mental health, coping, relationships, self-worth, pain, and senses) assessed by 35 items. AQoL-8D ranges from -0.04 to 1.00, with higher scores indicating better quality of life. |
| Change in Minimum Joint Space Width (JSW) | Up to 104 weeks | JSW is commonly used to assess knee OA progression and measured by X-ray imaging. Measurement of medial JSW was facilitated by the use of automated software that delineated the femoral and tibial margins of the joint. JSW(x) was measured at 4 fixed locations. These measures of medial JSW(x) were defined as the distance from the tibial margin to the femur margin at each fixed location on the x-coordinate system. Measurement of minimum JSW was made by the software at the location of the smallest distance between the femur and tibia margins in the medial compartment. |
Countries
Taiwan
Contacts
CONTACTChia-Ying Hsieh
PRINCIPAL_INVESTIGATORJih-Yang Ko
Chang Gung Memorial Hospital
STUDY_DIRECTORPo-Ting Wu
National Cheng-Kung University Hospital
STUDY_DIRECTORChih-Hao Chang
National Taiwan University Hospital
STUDY_DIRECTORKuo-Chin Huang
Chang Gung Memorial Hospital, Chiayi
Outcome results
None listed