Microbiota as Early Diagnostic and predictivE Factor for Osteoarthritic Degeneration and Microbial Contamination

NCT06944288 | Not Yet Recruiting DMC

• 1 other identifier: PNRR-MCNT2-2023-12377976
• Study Type: interventional
• Target: 170
• Locations: 0 countries
• Sites: N/A

Brief Summary

The patient(s) will participate in a clinical study that aims to investigate how the gut microbiota may influence the proper functioning of joints in the body and how it may affect the development of early osteoarthritis (OA), periprosthetic joint infection (PJI), and recovery after total joint replacement. In particular, the prevalence of early OA among patients with gut dysbiosis will be studied (Objective 1). The aim is to identify gut dysbiosis as a potential diagnostic factor for early OA. The study will analyze knee MRI scans and shoulder ultrasound images of 40 patients without musculoskeletal symptoms but with confirmed gut dysbiosis.In addition, the intra-articular microbiota in 50 patients undergoing total knee replacement will be investigated. Serum LPS levels during surgery and fecal microbiota before surgery and during postoperative recovery will be assessed (Objective 2). Postoperative recovery will be assessed based on criteria such as time off crutches and subjective scores. Finally, this will explore the correlation between gut microbiota and contaminating germs in periprosthetic infections. (Objective 3). 40 patients undergoing joint revision surgery for septic failure of a knee or hip replacement and 40 patients undergoing revision surgery for aseptic loosening for PJI will undergo gut microbiota analysis. Comparison between the two groups will allow evaluation of whether PJI causes changes in the gut microbiota. The patients will be included in the study under

• objective 1
• objective 2
• objective 3

Conditions

Knee Prosthesis; Knee Prosthesis Infection; Disbiosis

Outcome Measures

Primary Outcomes (3)

• Outcome 1 : to identify gut dysbiosis as a potential diagnostic tool for early OA.

  The study aims to establish gut dysbiosis as a potential diagnostic tool for early OA. If a strong association between gut dysbiosis and early OA is found, it could contribute to the development of a diagnostic protocol for early OA. The identification of gut dysbiosis as an early marker of OA could represent an additional diagnostic tool, allowing for early intervention and prevention of further progression of the disease. Early recognition of OA would allow a precocious and timely intervention which could positibely alter the natural history of this condition.

  1 year

• Outcome 2: to investigate the intraarticular microbiota, serum LPS levels during surgery, and fecal microbiota before surgery and during recovery.

  The analysis may reveal specific microbial imbalances or dysregulated pathways in the gut microbiota and serum LPS levels that are correlated with post-operative recovery outcomes. The study seeks to determine whether there is a correlation between the gut microbiota composition and post-operative recovery after total kneereplacement (TKA). It is expected that certain microbial taxa or functional pathways i n the gut microbiota will be associated with faster recovery, as indicated by shorter time taken to abandon crutches and higher subjective scores (e.g., KneeSociety Score, KSS score). The study aims to investigate the role of the gut microbiota as a predicting factor for joint arthroplasty recovery. If a significant correlation is found between specific microbial imbalances or dysregulated pathways and post-operative recovery outcomes, it could indicate that the gut microbiota can serve as a predictive factor for recoveryafter TKA.

  1 year

• Outcome 3: to investigate if periprosthetic joint infections (PJI) influences gut microbiota environment predisposing to gut dysbiosis, which negatively affects life expectancy in these patients.

  The analysis may reveal specific microbial imbalances or dysregulated pathways in the gut microbiota that are correlated with the presence of PJI. It is expected that patients with PJI will exhibit distinct alterations in the gut microbiota compared to patients undergoing revision surgery for aseptic mobilization. The analysis may establish a correlation between specific microbial taxa or functional pathways in the gut microbiota and the occurrence of PJI.

  1 year

Study Arms (1)

SURGERY

OTHER

TOTAL KNEE REPLACEMENT SURGERY AND REVISION SURGERY OF INFECTED KNEE PROSTHESIS

Procedure: total knee replacement

Interventions

total knee replacement PROCEDURE

The Orthopedic Surgeon will remove the damaged cartilage and bone then implant the new metal and plastic knee to restore the alignment and function of your knee. The surgical procedure takes about 1-2 hours on average. While in case of infection, an antibiotic cement is inserted, which will be removed with the subsequent prosthetic implant surgery. Finally, prosthetic components can be more filling, depending on the amount of bone that is previously removed.

SURGERY

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• proven gut dysbiosis (increased Firmicutes/Bacteroidetes (F/B) phyla ratio and increased permeability); age range 18-50 years old.
• patients undergoing total knee replacement surgery
• patients undergoing joint revision surgery for septic failure of a knee or hip prostheses; patients undergoing revision surgery for aseptic mobilization for PJI

You may not qualify if:

• musculoskeletal symptoms; previous shoulder or knee surgery; previous shoulder or knee known pathological conditions; rheumatological diseases
• any concurrent or previous diseases or conditions which might negatively affect the surgery
• major predisposing factor for gut dysbiosis (antibiotic therapy in the last 6 months, BMI \> 40 and inflammatory bowel disease); chronic inflammatory joint diseases (e.g., rheumatoid arthritis, psoriatic arthritis); acute (\< 90 days after the index procedure) and late hematogenous (symptoms of less than three weeks duration) infections; an inadequate amount of synovial fluid (\< 10 mL) for culture, WBC, and PMN (neutrophil) percentage determinations

Sponsors & Collaborators

• Istituto Clinico Humanitas: lead
• Azienda Ospedaliera di Rilievo Nazionale A.Cardarelli: collaborator

MeSH Terms

Conditions

Dysbiosis

Interventions

Arthroplasty, Replacement, Knee

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Arthroplasty, Replacement; Arthroplasty; Orthopedic Procedures; Surgical Procedures, Operative; Plastic Surgery Procedures; Prosthesis Implantation

Study Officials

• TOMMASO BONANZINGA

  Humanitas Research Hospital IRCCS, Rozzano-Milan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

ROBERTA TALLARITA

CONTACT

0282247770; roberta.tallarita@humanitas.it

LILIA LILIA DE CAROLIS

CONTACT

0282245206; lilia.decarolis@humanitas.it

Study Design

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

Model Details: Prosthesis surgery Revision of infected prosthesis

Study Record Dates

• First Submitted: April 7, 2025
• First Posted: April 25, 2025
• Study Start: February 1, 2026
• Primary Completion: April 1, 2026
• Study Completion (Estimated): May 30, 2026
• Last Updated: April 25, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP