Synovial Tissue as a Biomarker in the Early Management of Osteoarthritis

Overview

Osteoarthritis is a common disease whose prevalence continues to increase. To date, there is no medical treatment that has proven effective, and only symptomatic treatments exist, mainly to reduce pain. Arthroplasty, a costly and invasive surgical procedure, is often unavoidable in advanced stages of the disease. More than just a degenerative disease of the cartilage, osteoarthritis is now recognised as a heterogeneous disease causing multi-tissue damage of varying intensity. Synovitis plays a particularly important role in the onset and progression of osteoarthritis and has been closely correlated with radiographic severity, pain and loss of joint function. The investigators have identified several synovial histological pathotypes based on the type of synovial cell infiltrate and its distribution in samples from advanced osteoarthritis (surgical waste from prosthesis implantation). The investiogators' studies show that the presence of these pathotypes appears to be related to the clinical phenotype of patients. Analysis of synovial tissue at earlier stages of the disease is now essential to advance the understanding of the role of synovitis in osteoarthritis and its link to the clinical phenotype of patients. The objective of this protocol is to describe the different synovial histological pathotypes present in the early stages of osteoarthritis; To this end, the investigators will establish a cohort of osteoarthritis patients with a collection of synovial tissue samples obtained by ultrasound-guided needle biopsy in an outpatient setting, a well-tolerated procedure with simple follow-up, as well as blood sampling.

Detailed description

Osteoarthritis is a common disease whose prevalence continues to increase. It results from a variety of factors, such as ageing, excess weight and trauma, for example. To date, there is no medical treatment that has proven effective, and only symptomatic treatments exist, mainly to reduce pain. Arthroplasty, a costly and invasive surgical procedure, is often unavoidable in the advanced stages of the disease. More than just a degenerative disease of the cartilage, osteoarthritis is now recognised as a heterogeneous disease causing multi-tissue damage of varying intensity. Synovitis plays an important role in the initiation and progression of osteoarthritis and has been closely correlated with radiographic severity, pain and loss of joint function. The investigators have identified several synovial histological pathotypes based on the type of synovial cell infiltrate and its distribution in samples of advanced osteoarthritis (surgical waste from prosthesis implantation). The investigators' studies show that the presence of these pathotypes appears to be linked to the clinical phenotype of patients. Analysis of synovial tissue at earlier stages of the disease is now essential to advance our understanding of the role of synovitis in osteoarthritis and its link to the clinical phenotype of patients. The aim of this protocol is to describe the different synovial histological pathotypes present in the early stages of osteoarthritis; To this end, the investigators will establish a cohort of osteoarthritis patients and collect synovial tissue samples via ultrasound-guided needle biopsy in an outpatient setting, a well-tolerated procedure with simple after-effects, as well as blood samples. This procedure will be performed during an intra-articular injection scheduled as part of the patient's treatment. These samples will be used as part of a translational research project funded by the French National Research Agency (ANR). Patients' clinical data will be collected prospectively as part of a cohort study, including clinical and radiographic assessment of osteoarthritis. The objective of the study is to better understand the pathophysiological mechanisms governing the development of osteoarthritis within the synovial membrane in the early stages of the disease, thereby improving its management, identifying new therapeutic targets and paving the way for personalised medicine for patients suffering from osteoarthritis.

Interventions

• Other synovial biopsies
  The procedure for performing ultrasound-guided synovial biopsies is as follows: * This is performed under local anaesthetic, in the consultation room, under strict aseptic conditions in five stages. * After tracing anaesthesia up to the capsule, 2 to 3 mL of lidocaine are injected intra-articularly. * A 13G coaxial needle is then positioned in the joint cavity, allowing multiple biopsies to be performed without causing tissue damage along the needle path. * Samples are taken using a 14G semi-au

Primary outcome measures

• describe the different synovial histological pathotypes [Time frame: During visit inclusion]

Secondary outcome measures (8)

• Histological analyses of tissue to validate its quality [Time frame: during visit inclusion]
• Biopsy tolerance [Time frame: during visit inclusion]
• Patient acceptability of samples [Time frame: on the 15th day]
• Histological analyses to quantify synovial inflammatory infiltrate [Time frame: During visit inclusion]
• Analyses of the relationship between the extent and quality of cellular infiltration in histology and the intensity of synovitis determined by ultrasound [Time frame: During visit inclusion]
• High-throughput tissue analysis (single-cell sequencing, spatial transcriptomics) [Time frame: During visit inclusion]
• Effect of in vitro and ex vivo immune cell modulation strategies on synovial membrane explants [Time frame: On the 15th day]
• Analysis of the relationship between circulating and synovial immune populations [Time frame: During visit inclusion]

Eligibility criteria

Inclusion criteria

• Diagnosis of early osteoarthritis defined by the following clinical criteria:

• score ≤ 85% in at least two of the four categories of the KOOS questionnaire: pain, symptoms/signs, function and quality of life;
• presence of tenderness on palpation of the joint space or crepitus (clinical examination);
• Kellgren and Lawrence (KL) score of 0 or 3 (X-rays).
• Referred for therapeutic management including an intra-articular injection in the affected knee
• Patient affiliated with a social security scheme
• Patient able to understand the protocol and having signed an informed consent form.

Exclusion criteria

• Minors
• Adults under guardianship or trusteeship
• Pregnant women
• Breastfeeding women
• Protected patients
• Curative anticoagulation
• Thrombocytopenia < 50,000 platelets/mm3
• Patients who object to participating in the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Other

Study locations

France · 2 centers

• CHU de Nantes — Nantes
• CHU de Nantes — Nantes

Identifiers

NCT: NCT07473414 · RC25_0342

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗