Immuno-based Profiling of knEe OA Patients to Predict reSponse to Regenerative Treatment

Recruiting

• Conditions: Osteoarthritis, Knee
• Interventions: Procedure: platelet-rich plasma knee injection

• Registration Number: NCT06384040
• Lead Sponsor: Istituto Clinico Humanitas

Brief Summary

Osteoarthritis (OA) is a highly prevalent degenerative musculoskeletal disease and a major cause of chronic disability worldwide. Its multifactorial origin contributes to determine the heterogeneous phenotypes and one unmet need is the lack of biomarkers to predict the individual response. Platelet-rich-plasma (PRP) injection is a minimally invasive autologous blood-derived approach for which we plan to define specific knee profiles predictive of response. We will take advantage of a unique multidisciplinary approach aimed at analysing clinics, imaging, and biomarkers of associated with clinical response. We will focus on inflammatory (Wnt system, IL1 pathway, PTX3) and antioxidant (primarily, DPP3/Keap1/Nrf2) pathways. We foresee that our results will allow a better allocation of immunomodulatory and regenerative therapies for a personalized approach in knee OA thus maximising the effectiveness of the healthcare allocation.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-11-01
• Primary Completion: 2023-09-04
• Status Verified: 2024-04
• Study First Submitted: 2024-04-05
• Study First Submitted QC: 2024-04-22
• Study First Posted: 2024-04-25
• Last Update Submitted: 2024-04-26
• Last Update Posted: 2024-04-30
• Study Completion: 2024-10-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 105

Inclusion Criteria

• men/women, aged >40 - <75 years), OA grade 2-3, BMI <40, baseline WOMAC PAIN >1.75 -<4, >1 conservative therapy failed. Diagnosis of knee OA according to the American College of Rheumatology (ACR) classification criteria (Altman, 1986) .
• Ability to give informed consent.

Exclusion Criteria

• Presence of active infection or abnormal knee effusion on Day 1 at pre-injection of PRP
• Diagnosis of chronic inflammatory disease (i.e. rheumatoid arthritis, reactive arthritis, psoriatic arthritis, chondromalacia, arthritis secondary to other inflammatory diseases)
• Untreated acute traumatic injury, presence of a symptomatic meniscal tear, valgus/varus deformity judged by the investigator to be clinically significant, in the index knee
• Recent (within 3-6 months) arthroscopy, open surgery, intra-articular steroid injections, intra-articular hyaluronic acid (HA) injections, systemic steroid treatment, malignancy
• Any serious, non-malignant, significant, acute, or chronic medical condition or active psychiatric illness that, in the investigator's opinion, could compromise patient safety, limit the patient's ability to complete the study, and/or compromise the objectives of the study.
• Recent (within 30 days) use of any investigational drug or device prior to screening

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
PRP responder	platelet-rich plasma knee injection	response to treatment will be established in the presence of \>40% improvement of pain and/or motility
PRP non responder	platelet-rich plasma knee injection	response to treatment will be established in the presence of \<40% improvement of pain and/or motility

Primary Outcome Measures

Name	Time	Method
knee OA patients focusing on changes in Wnt and IL1-ß signalling and PTX3 expression	18 months	We will collect peripheral blood (PB) samples and cellular and molecular components in these samples will be characterized by measuring gene expression and protein levels of soluble factors involved in inflammatory pathways, with specific attention to Wnt and IL1 signaling pathways, and PTX3, and by performing a complete immunophenotype. We will use computational clustering approaches applied to single cell FACS data (Phenograph, FlowSOM, or similar) to identify phenotypic subsets in an unbiased way.

Secondary Outcome Measures

Name	Time	Method
To assess the overall oxidative status and antioxidant capacity of the enrolled OA patients and its possible prognostic role with respect to response to PRP treatment	36 months	We will define the overall oxidative status in the patients at baseline, by measuring a set of parameters related to enzymatic and non-enzymatic antioxidant systems, comprising the total antioxidant capacity, total glutathione, catalase activity, advanced glycation end products, HNE adducts, vitamin E and C, in the serum and SF, when available.

Trial Locations

Locations (1)

Istituto Clinico Humanitas; 🇮🇹 Rozzano, Milano, Italy