Comparison Between Intra-articular Infiltrations of PRP, MFAT, and PRP-MFAT in the Treatment of Symptomatic Knee Osteoarthritis. (MICROPREP3)

Randomized Control Trial Comparison Between Intra-articular Infiltrations of PRP, MFAT, and PRP-MFAT in the Treatment of Symptomatic Knee Osteoarthritis.

This research protocol evaluate the efficacity of intra-articular injections of autologous microfat associated with a preparation of autologous PRP, in symptomatic, resistant to first-line medical treatment, degenerative or post-traumatic cartilage lesions of the knee.

The primary objective of this study is to show the superiority of intra-articular injection of autologous microfat combined with autologous PRP preparation compared to injection of microfat or PRP used alone, on the KOOS score at 6 months.

Study Overview

• Status: Not yet recruiting
• Conditions: Osteo Arthritis Knee
• Intervention / Treatment: Biological: Intra-articular injection of autologous microfat; Biological: Intra-articular injection of autologous platelet-rich plasma; Biological: Intra-articular injection of autologous microfat and platelet-rich plasma

Detailed Description

Osteoarthritis is the most widespread joint disease in the world, and one of the most frequent causes of pain and functional disability in Western countries. The incidence of cartilage lesions is constantly on the rise, due to the ageing of the population and the traumas associated with the development of sporting activities.

Recently, the emergence of biotherapies in orthopaedics has led to the development of intra-articular injections of autologous platelet-rich plasma (PRP). Their use has been widespread since 2010, based on the demonstration that platelet-enriched plasma, a concentrate of growth factors, can stimulate cartilage regeneration in vitro and in vivo in preclinical models (Saito, Schmidt, Qi, Tchetina). In addition, PRP administration methods can be optimized: since it is a liquid preparation (platelet suspension), administering it within an interface tissue limits its diffusion and potentiates its trophic effect on the injured cartilage site. Adipose tissue represents the most relevant tissue of interest, as it is a stem cell-rich support tissue with full therapeutic potential, and is easily accessible. Thus, a sample of autologous "microfat" (adipose tissue containing small fat lobules and stem cells, harvested under local anaesthetic by manual liposuction using specific fine sampling cannulas) co-administered at the level of the synovial capsule, could play the role of fluid trophic matrix to the PRP.

The hypothesis of this project is that the standardized injection of an innovative treatment (microgrease and autologous PRP dose) can defer the need for knee arthroplasty in patients with gonarthrosis resistant to first-line medical treatment. The investigators propose to carry out a clinical study in patients with chondral knee lesions resistant to first-line medical treatment, evaluating the benefit during follow-up of treatment with intra-articular injections of microfat and a standardized preparation of autologous PRP or the combination of the 2.

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Alexandra GIULIANI; Phone Number: 0491382870; Email: alexandra.giuliani@ap-hm.fr
• Study Contact Backup: Name: Alexandre ROCHWERGER, Pr; Phone Number: 04 91 96 63 00; Email: richardalexandre.rochwerger@ap-hm.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients of both gender, between 20 and 75 year-old.
• Symptomatics degenerativ or post traumatic chondropathy, on at least one of the 3 knee compartments ICRS grade 2, 3 or 4 with VAS>4 and failure of well-conducted medical treatment for at least 1 year (palliative analgesics adapted to the pain, AINS, rehabilitation by a physiotherapist, injections intra-articulaires de corticoïdes et/ou d'acide hyaluronique)
• Varus or valgus less than or equal to 5°.
• BMI greater than 20 (in order to have sufficient fatty tissue)
• Informed consent signed by the patient
• HB > 10g/dl
• Negative beta-HCG at inclusion and effective contraception for patients of childbearing age, for 1 month.
• Beneficiaries of or affiliated to a social security system

Exclusion Criteria:

• Contraindications to MRI : ocular foreign bodies, pacemaker, neurostimulator, cochlear implant, vascular clips, metallic heart valve
• Body mass index (BMI) of less than 20 kg/m2 not allowig to obtain a sufficient quantity of adipose tissue.
• Thrombocytopenia < 150 G/L
• Thrombocytosis > 450 G/L
• Known thrombopathy
• TP=> PR < 70%.
• TCA=> APR > 1.20s
• Anemia HB < 10g/dl
• Positive markers for the following active infectious diseases: HIV 1 and HIV 2 human immunodeficiency virus infection; HTLV I and II virus infection; Hepatitis B virus infection; Hepatitis C virus infection; Syphilis causative agent infection.
• Use of antiplatelet agents, aspirin, anti-vitamin K drugs for less than 15 days.
• Chronic treatment with oral corticosteroids or the use of such treatment less than 2 weeks prior to inclusion
• Intra-articular corticosteroid injection less than 2 months prior to inclusion
• Intra-articular injection of hyaluronic acid less than 2 months prior to inclusion
• Non-steroidal anti-inflammatory drugs less than 15 days prior to inclusion
• Recent fever or infection (bacterial or viral) less than one month old
• Autoimmune diseases
• Inflammatory arthritis
• Immune deficiency
• Ongoing or chronic infectious diseases (viral or bacterial)
• T Malignant tumours or history of malignant tumours less than 5 years prior to inclusion
• Pregnant or lactating women
• Adults protected by law (guardianship or curatorship)
• Patient participating simultaneously in another research project involving the human person
• Minors
• Persons residing in a health or social institution
• Persons in emergency situations
• Persons deprived of liberty
• Persons not covered by the French social security scheme
• Contraindication to local anesthesia and/or surgery
• Allergy to local anesthetics
• Inmates

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: autologous microfat (MG); Patient will be hospitalized in outpatient surgery. A blood sample will be collected and a lipoaspiration will be performed under local anesthesia during the same operation by the nurses and the surgeon. Then, biological products will be immediately prepared, and a preparation of autologous MG will be injected intra-articularly by th same surgeon.	Biological: Intra-articular injection of autologous microfat; A preparation of autologous microfat (5mL) will be injected intra-articularly.
Experimental: Platelet-rich plasma (PRP); Patient will be hospitalized in outpatient surgery. A blood sample will be collected and a lipoaspiration will be performed under local anesthesia during the same operation by the nurses and the surgeon. Then, biological products will be immediately prepared, and a preparation of autologous PRP will be injected intra-articularly by th same surgeon.	Biological: Intra-articular injection of autologous platelet-rich plasma; A preparation of autologous platelet-rich plasma (5mL) will be injected intra-articularly.
Experimental: Microfat autologous-Platelet-rich plasma (MG-PRP); Patient will be hospitalized in outpatient surgery. A blood sample will be collected and a lipoaspiration will be performed for the preparation during the same operation by the nurses and the surgeon. Then, biological products will be immediately prepared, and autologous microfat associated with a preparation of autologous PRP will be injected intra-articularly by th same surgeon.	Biological: Intra-articular injection of autologous microfat and platelet-rich plasma; A preparation of autologous platelet-rich plasma (5mL) and autologous microfat (5mL) will be injected intra-articularly.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
KOOS score at 6 months	KOOS assesses the short- and long-term consequences of knee injuries, as well as the consequences of primary osteoarthritis. It is percentage from 0 to 100. 0 represents extreme problems and 100 represents no problem.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain at 1 month	Pain will assassed by a visual anatomy scale from 0 (no pain) to 10 (pain as bad as it could possibly be)	1 month
Pain at 3 months	Pain will assassed by a visual anatomy scale from 0 (no pain) to 10 (pain as bad as it could possibly be)	3 months
Pain at 12 months	Pain will assassed by a visual anatomy scale from 0 (no pain) to 10 (pain as bad as it could possibly be)	12 months
KOOS score at 1 month	KOOS assesses the short- and long-term consequences of knee injuries, as well as the consequences of primary osteoarthritis. It is percentage from 0 to 100. 0 represents extreme problems and 100 represents no problem.	1 month
KOOS score at 3 months	KOOS assesses the short- and long-term consequences of knee injuries, as well as the consequences of primary osteoarthritis. It is percentage from 0 to 100. 0 represents extreme problems and 100 represents no problem.	3 months
KOOS score at 12 months	KOOS assesses the short- and long-term consequences of knee injuries, as well as the consequences of primary osteoarthritis. It is percentage from 0 to 100. 0 represents extreme problems and 100 represents no problem.	12 months
Proportion of treatment failures	Patients are defined as treatment failures if, during the follow-up period, they undergo one of the following procedures on the treated knee, in the absence of intercurrent events: new injection (whatever the product injected), arthroscopy, arthroplasty, etc.	12 months
Proportion of arthroplasties not performed in arthroplasty candidates		12 months

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille

Study record dates

Study Major Dates

• Study Start (Estimated): February 2, 2024
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: October 10, 2023
• First Submitted That Met QC Criteria: October 10, 2023
• First Posted (Actual): October 16, 2023

Study Record Updates

• Last Update Posted (Actual): October 27, 2023
• Last Update Submitted That Met QC Criteria: October 26, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: RCAPHM21_0431

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No