Bone Marrow Versus Adipose Tissue as a Cell Source for Infiltrative Treatment of Knee Osteoarthritis

Official title

Bone Marrow vs Adipose Tissue as a Cell Source for Infiltrative Treatment of Knee Osteoarthritis: Randomized Clinical Trial

Overview

The MAST-GR study is a randomized controlled interventional trial with parallel treatment arms and 1:1 allocation The primary objective of the study is to compare the safety and efficacy of a single intra-articular infiltration of Bone marrow aspirate concentrate (BMAC) with one of minimally manipulated adipose tissue (MM-AT) so as to determine the most effective cellular product in treating patients with knee osteoarthritis (OA). The secondary objective is to demonstrate whether intra-articular infiltration of BMAC or MM-AT can induce disease-modifying effects in knee OA by imaging and biological assessments on peripheral blood. The tertiary objective of the study is to identify factors that influence the clinical response to treatment (baseline characteristics of patients, biological characteristics of the treated knee, characteristics of cellular products, BMAC and MM-AT).

Detailed description

Patients with symptomatic unilateral knee OA will be included in a randomized controlled Trial (RCT), in which one group of patients will be treated with 1 intra-articular infiltration of BMAC, and one group will be treated with 1 intra-articular infiltration of MM-AT. A total of 204 patients will be included and will undergo infiltrative treatment after collecting informed consent for study participation and master data. Patients will be clinically evaluated at 0-2-6-12 months follow-up. Possible disease-modifying effects of the two cell products will be investigated by analysis on peripheral blood at 0-2-6-12 months follow-up and by evaluation of radiographic and magnetic resonance imaging (MRI) at 0 and 12 months follow-up. In addition, characterization of the portion of BMAC and MM-AT remaining from treatment will be carried out, as well as baseline assessment of peripheral blood on all patients, and synovial fluid and synovial membrane, where possible, to analyze their influence on clinical outcome.

Interventions

• Biological Bone marrow aspirate concentrate injection
  single intra-articular injection of Bone Marrow aspirate concentrate derived from the patient's iliac crest
• Biological intra-articular injection of Minimally manipulated adipose tissue
  single intra-articular injection of Minimally manipulated adipose tissue derived from the patient's abdominal adipose tissue

Primary outcome measures

• Western Ontario and McMaster University Osteoarthritis index (WOMAC) - Pain subscale [Time frame: 6 months follow-up]

Secondary outcome measures (12)

• Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) [Time frame: baseline, 2 months, 6 months, 12 months follow-up]
• Knee Injury and Osteoarthritis Outcome Score (KOOS) [Time frame: baseline, 2 months, 6 months, 12 months follow-up]
• Visual Analogue Scale (VAS) [Time frame: baseline, 2 months, 6 months, 12 months follow-up]
• EuroQol Visual Analogue Scale (EQ-VAS) [Time frame: baseline, 2 months, 6 months, 12 months follow-up]
• Tegner Activity Level Scale [Time frame: baseline, 2 months, 6 months, 12 months follow-up]
• Objective parameters- Range of Motion [Time frame: baseline, 2 months, 6 months, 12 months follow-up]
• Objective parameters - Circumferences [Time frame: baseline, 2 months, 6 months, 12 months follow-up]
• Patient Acceptable Symptom State (PASS) [Time frame: baseline, 2 months, 6 months, 12 months follow-up]
• Minimally Clinical Important Difference (MCID) [Time frame: baseline, 2 months, 6 months, 12 months follow-up]
• Expectations about the effectiveness of the treatment [Time frame: baseline]
• Kellgren-Lawrence score [Time frame: baseline, 12 months follow-up]
• 3 Tesla Nuclear Magnetic Resonance Imaging (3T MRI) [Time frame: baseline, 12 months follow-up]

Eligibility criteria

Inclusion criteria

Patients with symptomatic unilateral knee OA with:

• Men or women aged 40 to 75 years;
• Signs and symptoms of OA with a clinical history of gonalgia or swelling for at least 6 months;
• Radiographic signs of OA (Kellgren-Lawrence grade 1-4);
• No benefit after at least 4 months of conservative treatment;
• Ability and consent of patients to actively participate in clinical and radiological (rx and MRI) follow-up;
• Signing of informed consent.

Exclusion criteria

• Patients unable to express consent;
• Patients aged < to 40 and > to 75 years;
• Patients with axial deviations > 5°;
• Patients who have suffered trauma or undergone intra-articular infiltration of other substance in the previous 6 months;
• Patients who have undergone knee surgery in the previous 12 months;
• Patients with concomitant knee injuries causing joint pain or swelling (-focal full-thickness osteochondral defects, acute meniscal injuries);
• Patients with malignant neoplasms;
• Patients with uncompensated systemic diseases (rheumatic diseases, metabolic disorders such as diabetes and thyroid diseases);
• Patients with infectious diseases;
• Patients with histories of alcohol or drug abuse;
• Patients who are pregnant;
• Patients with allergies to anesthetics used in the procedure.

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

Single blind

Primary purpose

Treatment

Study locations

Italy · 1 center

• Istituto Ortopedico Rizzoli — Bologna

Publications

• Anz AW, Hubbard R, Rendos NK, Everts PA, Andrews JR, Hackel JG. Bone Marrow Aspirate Concentrate Is Equivalent to Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis at 1 Year: A Prospective, Randomized Trial. Orthop J Sports Med. 2020 Feb 18;8(2):2325967119900958. doi: 10.1177/2325967119900958. eCollection 2020 Feb. PMID 32118081
• Basile M, Rumi F, Palmeri M, Mattozzi I, Manzoli L, Mammucari M, Gigliotti S, Bernabei R, Cicchetti A. Il burden economico dell'inappropriatezza prescrittiva nella gestione dell'osteoartrite in Italia. Glob Reg Health Technol Assess. 2020 Dec 10;7:101-108. doi: 10.33393/grhta.2020.2130. eCollection 2020 Jan-Dec. Italian. PMID 36627953
• Boffa A, Merli G, Andriolo L, Lattermann C, Salzmann GM, Filardo G. Synovial Fluid Biomarkers in Knee Osteoarthritis: A Systematic Review and Quantitative Evaluation Using BIPEDs Criteria. Cartilage. 2021 Dec;13(1_suppl):82S-103S. doi: 10.1177/1947603520942941. Epub 2020 Jul 25. PMID 32713185
• Boffa A, Di Martino A, Andriolo L, De Filippis R, Poggi A, Kon E, Zaffagnini S, Filardo G. Bone marrow aspirate concentrate injections provide similar results versus viscosupplementation up to 24 months of follow-up in patients with symptomatic knee osteoarthritis. A randomized controlled trial. Knee Surg Sports Traumatol Arthrosc. 2022 Dec;30(12):3958-3967. doi: 10.1007/s00167-021-06793-4. Epub 2 PMID 34767030
• Cai X, Yuan S, Zeng Y, Wang C, Yu N, Ding C. New Trends in Pharmacological Treatments for Osteoarthritis. Front Pharmacol. 2021 Apr 15;12:645842. doi: 10.3389/fphar.2021.645842. eCollection 2021. PMID 33935742
• Caplan AI, Correa D. The MSC: an injury drugstore. Cell Stem Cell. 2011 Jul 8;9(1):11-5. doi: 10.1016/j.stem.2011.06.008. PMID 21726829
• Carelli S, Messaggio F, Canazza A, Hebda DM, Caremoli F, Latorre E, Grimoldi MG, Colli M, Bulfamante G, Tremolada C, Di Giulio AM, Gorio A. Characteristics and Properties of Mesenchymal Stem Cells Derived From Microfragmented Adipose Tissue. Cell Transplant. 2015;24(7):1233-52. doi: 10.3727/096368914X681603. Epub 2014 May 6. PMID 24806078
• Cavallo C, Boffa A, Andriolo L, Silva S, Grigolo B, Zaffagnini S, Filardo G. Bone marrow concentrate injections for the treatment of osteoarthritis: evidence from preclinical findings to the clinical application. Int Orthop. 2021 Feb;45(2):525-538. doi: 10.1007/s00264-020-04703-w. Epub 2020 Jul 13. PMID 32661635

Identifiers

NCT: NCT06040957 · MAST-GR

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗