Clinical trial NCT03825133: The Comparison of Knee Osteoarthritis Treatment With Bone Marrow Aspirate Concentrate , Leukocyte Rich Platelet Rich Plasma and Hyaluronic Acid
Official title: The Comparison of Knee Osteoarthritis Treatment With Single-dose of Bone Marrow Aspirate Concentrate, Single-dose of Leukocyte Rich Platelet Rich Plasma and 3 Injection of High Molecular Weight Hyaluronic Acid-A Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Knee Osteoarthritis
Lead sponsor: Clinical Center of Vojvodina
Sponsor class: OTHER
First posted: 2019-01-31
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be randomly assigned to 3 groups: LR-PRP group, the BMAC group or HA group. Functional scores and outcomes will be compared to determine clinical efficacy of all groups and which treatment is more effective in treating knee OA
Primary purpose: TREATMENT

Brief summary: The aim of this study is to compare therapeutic and clinical effects of intra-articular injection of Bone Marrow Aspirate Concentrate (BMAC), inta-articular injection of Leukocyte Rich Platelet Rich plasma (LR-PRP) and 3 weekly doses of high molecular weight of Hyaluronic acid for the treatment of osteoarthritis (OA) of the knee ( KL scale II-IV).

Detailed description: Osteoarthritis (OA) is the most common joint disease worldwide, affecting an estimated 10% of men and 18% of women over 60 years of age with the knee and hip joints predominantly involved. The pain and loss of function can be debilitating; in developed countries the resultant socioeconomic burden is large costing between 1, 0% and 2, 5% of gross domestic product. Several therapeutic options for the treatment of OA are widely used, consists of pain management, physical therapy with life-modifying recommendations, joint injections with joint replacement for end-stage disease. Intra-articular drug delivery has several advantages over systemic delivery, including increased local bioavailability, reduced systemic exposure, fewer adverse events and reduced cost. Three injectable materials have been widely used for intra-articular treatment of the knee OA: corticosteroids (with or without local anesthetics), hyaluronic acid based preparations and in the last decade biologic preparations, such as human serum albumin, TNF and Il-1 inhibitors, platelet-rich plasma (PRP) injections, bone marrow-derived stem cells (BMSCs), adipose-derived stem cells (ADSCs) and amnion-derived mesenchymal stem cells (AMSCs) etc PRP is promising therapeutic option for the OA treatment, there are still many concerns with PRP's efficiency. Among all questions, ( Number of platelets, percentage in accordance with baseline, frequency of doses etc.) presence or absence of different cells in PRP formulations ( as leukocytes), could significantly change an overall clinical result. In general, PRP could be Leukocyte-rich (LR- with increase number of Leukocytes in comparison with baseline number) and Leukocyte-poor.

Another option that has become more popular for physicians treating this debilitation condition is BMAC, which use undifferentiated cells found in the bone marrow to promote healing and tissue regeneration. These cells have the ability to replicate into a multiple different tissue types. With BMAC, the marrow is concentrated provide better healing of the damaged tissue and aid in growth and repair. The full benefits of BMAC are still unknown, but studies have shown the treatment can reduce swelling, relieve pain, and improve healing in articular cartilage and bone grafts.

Autologous BMAC has shown promising clinical potential as a therapeutic agent in regenerative medicine, including the treatment of osteoarthritis and cartilage defects, and the clinical efficacy platelet rich plasma has been documented to alleviate symptoms related to knee osteoarthritis. However, randomized, prospective comparison of the two techniques has not been reported in the literature and long term follow-up for both treatments is limited, and especially limited in the use of BMAC for the knee OA treatment.

From the other hand, HA preparations are widely used in everyday practice for almost 30 years with variable results. No one of these therapeutic options are not yet recommended by supreme professional organizations ( e.g.AAOS) because of paulacity of scientific data and unbiased confirmation of their clinical efficiency with a broad advice for necessity of more rigorous clinical trials.

Eligibility criteria: Inclusion Criteria:

* history of complaints of knee pain because of the Knee Osteoarthritis with no relief using anti-inflammatory agents even after 3 months,
* Kellgren-Lawrence (KL) grade 2-4
* normal blood results and coagulation profile (platelets 150,000-450,000/l),
* patients who had not undergone any surgery on the affected knee within 2 years prior to the first injection and
* Mentally fit for clinical study

Exclusion Criteria:

* severe knee instability,
* severe misalignment,
* unicompartmental OA
* BMI more than 35
* inflammatory arthritis such as rheumatoid arthritis and ankylosing spondylitis
* presenting muscle pain underlying diseases such as hematologic disorders, septicemia, coagulopathy, neoplasm, active infection, and immune deficiency

Primary outcomes:
measure: change of WOMAC
timeFrame: after 1, 3, 6, 9 and 12 months
measure: Change of KOOS
timeFrame: after 1, 3, 6, 9 and 12 months
Secondary outcomes:
measure: change of SF-36
timeFrame: after 1, 3, 6, 9 and 12 months
measure: Change of IKDC
timeFrame: after 1, 3, 6, 9 and 12 months
measure: change of VAS pain
timeFrame: after 3, 7 14 and 21 days
measure: VAS pain injection
timeFrame: up to 10 minutes after after intervention
measure: VAS score after injection of fluid
timeFrame: up to 10 minutes after after intervention
Other outcomes:
measure: Knee injection portals influence on final clinical results.
timeFrame: after one year
Locations:
city: Novi Sad
country: Serbia
facility: Clinical Center of Vojvodina
state: Vojvodina
Study officials:
References:
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