Clinical trial NCT03790189: Subchondral and Intra-articular Application of Bone Marrow Concentrate for Knee Unicompartmental OA
Official title: Subchondral and Intra-articular Application of Bone Marrow Concentrate as a Treatment Strategy for Knee Unicompartmental Osteoarthritis (OA): a Pilot Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Osteoarthritis, Knee
Cartilage Degeneration
Keywords: knee
unicompartmental osteoarthritis
injection
subchondroplasty
bone marrow concentrate
mesenchymal stem cells
Lead sponsor: Istituto Clinico Humanitas
Sponsor class: OTHER
First posted: 2018-12-31
Enrollment: 25
Sex: ALL
Minimum age (years): 35
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change in IKDC (International Knee Documentation Committee) subjective score
timeFrame: baseline vs 12 months' follow-up
Secondary outcomes:
measure: Variation in KOOS (Knee Injury and Osteoarthritis Outcome) Score
timeFrame: baseline vs 12 months' follow-up
measure: VAS (Visual Analogue Scale) for pain
timeFrame: baseline vs 12 months' after treatment
measure: MRI (Magnetic Resonance Imaging) Changes in subchondral bone edema and cartilage status from basal to 12 months' follow-up
timeFrame: baseline vs 12 months' follow-up
Other outcomes:
Locations:
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Milano
Study officials:
affiliation: Istituto Clinico Humanitas, Rozzano, Italy
name: Elizaveta Kon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Istituto Clinico Humanitas, Rozzano, Italy
name: Berardo Di Matteo, MD
role: STUDY_DIRECTOR
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