Subchondral and Intra-articular Application of Bone Marrow Concentrate for Knee Unicompartmental OA (MarrowMule)

Istituto Clinico Humanitas

Status: Unknown

Conditions: Cartilage Degeneration; Osteoarthritis, Knee

Treatments: Biological: Subchondral and intra-articular injection of BMC

Study type: Interventional

Funder types: Other

Identifiers

NCT03790189

172797

Details and patient eligibility

About

Unicompartmental knee osteoarthritis (OA) is a common finding especially in patients with lower limb malalignment and previous meniscectomy. Among the various treatment options, in recent years there has been an increasing attention towards the use of biologic agents, such as platelet rich plasma and mesenchymal stem cells, as intra-articular injective approaches to relieve pain and restore joint function. Anyway, the sole intra-articular administration of these agents may not lead to satisfactory outcome in a relevant percentage of patients. In fact, unicompartmental osteoarthritis is not only characterized by degeneration of the articular cartilage, but also by pathologic changes in the subchondral bone, both at the tibial plateaux and in the femoral condyle. Magnetic resonance imaging reveals, in many cases, alterations of the subchondral tissue known as "bone marrow edema", which is a sign of bone overload and play a significant role in the progression of unicompartmental OA and is responsible of OA-related symptoms. Therefore, concurrent treatment of both the subchondral bone damage and intra-articular degeneration could led to better outcome for patients affected by unicompartmental OA: the aim of the present pilot trial is to assess the safety and describe the clinical outcome following concurrent intra-articular and subchondral bone application of Bone Marrow Concentrate (BMC). BMC is an autologous product rich in mesenchymal stem cells, which have immuno-modulatory and throfic properties and are able to restore the joint homeostasis by reducing the inflammatory distress traditionally associated to OA.

BMC will be collected directly in the operating room from the anterior iliac crest or the tibia by using the MARROW CELLUTION kit (Geistlich, Switzerland), which allows to obtain BMC without the need of centrifugation processes. Approximately 9-10 ml of BMC will be harvested: 6 ml will be injected, under fluoroscopic guidance, in the tibial emiplateaux (approx 3 ml) and in the femoral condyle (approx 3 ml) presenting MRI evidence of bone marrow edema. The remaining amount of BMC will be administered intra-articularly to address articular tissues (cartilage, menisci and synovium). Twenty-five patients affected by unicompartmental knee OA will be included in the present pilot trial and treated in a "Day-Surgery" regimen. They will be followed up at 3, 6, and 12 months' after treatment by clinical questionnaires and radiographic evaluations (x-rays at 6 and 12 months, MRI at 12 months' f-up). Any intra-op and post-op adverse events will be documented.

Enrollment: 25 estimated patients

Sex: All

Ages: 35 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• chronic symptomatic (at least 6 months) medial or lateral unicompartmental OA of the knee, with Kellgren-Lawrence Score evaluated at x-rays= 2 or 3;
• MRI evidence of "bone marrow edema" affecting the subchondral bone of the tibial emiplateaux and femoral condyle;
• failure of previous conservative treatments in the same knee (e.g: pharmacological therapy, physiotherapy, previous intra-articular injections, etc..);
• willingness to participate in the trial, including all follow-up visits and radiographic examinations.

Exclusion criteria

• medial or lateral unicompartmental OA with Kellgren-Lawrence score= 1 or 4 (i.e. early osteoarthritis or end-stage osteoarthritis);
• no MRI evidence of bone marrow edema in the affected knee compartment;
• concurrent rheumatic or other immunological diseases;
• concurrent malignancies;
• bilateral symptomatic knee OA;
• concurrent patello-femoral OA;
• BMI>35
• any surgical treatment in the index knee within 12 months from the screening visit.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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25 participants in 1 patient group

Bone Marrow Concentrate

Experimental group

Description:

Bone Marrow concentrate will be injected intra-articularly and at the bone-cartilage interface both in the tibia and femur of patients affected by unicompartmental knee osteoarthritis

Treatment:

Biological: Subchondral and intra-articular injection of BMC