Intra Articular Injection of Peripheral Blood Mononuclear Cells for Knee Osteoarthritis

Official title

Peripheral-blood Cell Purification for PBMCs (PCP-PBMCs) Injection for Knee Osteoarthritis (PCP-PBMCs-KOA)

Overview

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

• Biological High-dose PCP-PBMCs injection
  4 mL 100-200 million PCP-PBMCs injection into synovial cavity
• Drug Solu-Medrol
  4 mL solu-medrol solution, injected into synovial cavity
• Biological Low-dose PCP-PBMCs injection
  4 mL 20-60 million PCP-PBMCs injection into synovial cavity

Primary outcome measures

• Mean Change in Numeric Rating Scale (NRS) Score [Time frame: Up to 52 weeks]
• Changes in scores on the Knee injury and Osteoarthritis Outcome Score (KOOS) [Time frame: Up to 52 weeks]

Secondary outcome measures (6)

• Mean Change in Numeric Rating Scale (NRS) Score [Time frame: Up to 104 weeks]
• Changes in scores on the Knee injury and Osteoarthritis Outcome Score (KOOS) [Time frame: Up to 104 weeks]
• Mean Change in the Visual Analog Scale (VAS) [Time frame: Up to 104 weeks]
• Changes in scores on the Intermittent and Constant Osteoarthritis Pain (ICOAP) questionnaire [Time frame: Up to 104 weeks]
• Changes in scores on the Assessment of Quality of Life 8 Dimension (AQoL-8D) [Time frame: Up to 104 weeks]
• Change in Minimum Joint Space Width (JSW) [Time frame: Up to 104 weeks]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Taiwan · 4 centers

• Chang Gung Memorial Hospital, Chiayi — Chiayi City
• Kaohsiung Chang Gung Memorial Hospital — Kaohsiung City
• National Cheng Kung University Hospital — Tainan
• National Taiwan University Hospital — Taipei

Identifiers

NCT: NCT07703280 · PBMC-KOA

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗