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

NCT03790189 | Unknown DMC

• 1 other identifier: 172797
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

Osteoarthritis, Knee; Cartilage Degeneration

Keywords

knee; unicompartmental osteoarthritis; injection; subchondroplasty; bone marrow concentrate; mesenchymal stem cells

Outcome Measures

Primary Outcomes (1)

• Change in IKDC (International Knee Documentation Committee) subjective score

  IKDC subjective score is a validated clinical questionnaire (available also in Italian) designed to assess the functional status of the knee by a series of 10 items. The IKDC subjective score assess the overall function of the knee as subjectively evaluated by the patient who needs to answer a series of questions concerning symptoms and his/her activity level. It ranges from 0 to 100 points, with higher values representing a better knee status.

  baseline vs 12 months' follow-up

Secondary Outcomes (3)

• Variation in KOOS (Knee Injury and Osteoarthritis Outcome) Score

  baseline vs 12 months' follow-up

• VAS (Visual Analogue Scale) for pain

  baseline vs 12 months' after treatment

• MRI (Magnetic Resonance Imaging) Changes in subchondral bone edema and cartilage status from basal to 12 months' follow-up

  baseline vs 12 months' follow-up

Study Arms (1)

Bone Marrow Concentrate

EXPERIMENTAL

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

Biological: Subchondral and intra-articular injection of BMC

Interventions

Subchondral and intra-articular injection of BMC BIOLOGICAL

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

Bone Marrow Concentrate

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Istituto Clinico Humanitas: lead

Study Sites (1)

Istituto Clinico Humanitas

Rozzano, Milano, 20089, Italy

RECRUITING

Related Publications (7)

• Sanchez M, Delgado D, Sanchez P, Muinos-Lopez E, Paiva B, Granero-Molto F, Prosper F, Pompei O, Perez JC, Azofra J, Padilla S, Fiz N. Combination of Intra-Articular and Intraosseous Injections of Platelet Rich Plasma for Severe Knee Osteoarthritis: A Pilot Study. Biomed Res Int. 2016;2016:4868613. doi: 10.1155/2016/4868613. Epub 2016 Jul 4.

  PMID: 27462609 BACKGROUND

• Kwan Tat S, Lajeunesse D, Pelletier JP, Martel-Pelletier J. Targeting subchondral bone for treating osteoarthritis: what is the evidence? Best Pract Res Clin Rheumatol. 2010 Feb;24(1):51-70. doi: 10.1016/j.berh.2009.08.004.

  PMID: 20129200 BACKGROUND

• Dray A, Read SJ. Arthritis and pain. Future targets to control osteoarthritis pain. Arthritis Res Ther. 2007;9(3):212. doi: 10.1186/ar2178.

  PMID: 17561993 BACKGROUND

• Pan J, Wang B, Li W, Zhou X, Scherr T, Yang Y, Price C, Wang L. Elevated cross-talk between subchondral bone and cartilage in osteoarthritic joints. Bone. 2012 Aug;51(2):212-7. doi: 10.1016/j.bone.2011.11.030. Epub 2011 Dec 16.

  PMID: 22197997 BACKGROUND

• Sanchez M, Fiz N, Guadilla J, Padilla S, Anitua E, Sanchez P, Delgado D. Intraosseous infiltration of platelet-rich plasma for severe knee osteoarthritis. Arthrosc Tech. 2014 Dec 15;3(6):e713-7. doi: 10.1016/j.eats.2014.09.006. eCollection 2014 Dec.

  PMID: 25685680 BACKGROUND

• Pretzel D, Linss S, Rochler S, Endres M, Kaps C, Alsalameh S, Kinne RW. Relative percentage and zonal distribution of mesenchymal progenitor cells in human osteoarthritic and normal cartilage. Arthritis Res Ther. 2011 Apr 15;13(2):R64. doi: 10.1186/ar3320.

  PMID: 21496249 BACKGROUND

• Hernigou P, Auregan JC, Dubory A, Flouzat-Lachaniette CH, Chevallier N, Rouard H. Subchondral stem cell therapy versus contralateral total knee arthroplasty for osteoarthritis following secondary osteonecrosis of the knee. Int Orthop. 2018 Nov;42(11):2563-2571. doi: 10.1007/s00264-018-3916-9. Epub 2018 Mar 27.

  PMID: 29589086 BACKGROUND

MeSH Terms

Conditions

Osteoarthritis, Knee

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Study Officials

• Elizaveta Kon, MD

  Istituto Clinico Humanitas, Rozzano, Italy

  PRINCIPAL INVESTIGATOR

• Berardo Di Matteo, MD

  Istituto Clinico Humanitas, Rozzano, Italy

  STUDY DIRECTOR

Central Study Contacts

Berardo Di Matteo, MD

CONTACT

+390282245425; berardo.dimatteo@gmail.com

Laura Lovato, MS

CONTACT

laura.lovato@hunimed.eu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2018
• First Posted: December 31, 2018
• Study Start: January 1, 2019
• Primary Completion: July 1, 2021
• Study Completion: November 1, 2021
• Last Updated: December 31, 2018

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)