Physiopathology of Prosthetic Joint Infections (PROTHEE-PILOTE)

Physiopathology of Prosthetic Joint Infections : a Pilot Study

This study aim to explore cellular responses of bone and immune cells to bacterial infections observed in patients with prosthetic joint infections. The investigators will analyze clinical data and tissue samples collected from patients undergoing surgery as part of their usual care for prosthetic joint infections. These research will be conducted on three different hospitals in Paris: Lariboisière (AP-HP), Cochin (AP-HP) and Croix Saint-Simon.

Study Overview

• Status: Not yet recruiting
• Conditions: Prosthetic-joint Infection

Detailed Description

The number of prosthetic joint infections (PJI) new cases in France is estimated at 2000/2500 cases per year. PJI, mainly caused by staphylococci, are serious infections responsible for significant morbidity result of inflammation and bone destruction (osteomyelitis). Despite optimal medical and surgical management, a risk of failure and recurrence exists, which varies depending on the situation.

In addition to the deterioration in patients' quality of life, the economic cost for the health care system is very high, in particular because of prolonged hospitalizations, complex treatments, and frequent readmissions. Thus, the adequate management of PJI is a major public health issue.

In this context, new therapeutic approaches are urgent medical needs for the management of patients with PJI.

Thus, the identification of the biological mechanisms (immunology, microbiology, bone physiology) underlying these infections is essential. Indeed, the impact of bacterial infections on bone homeostasis is poorly documented. Although several biological mechanisms have been suggested the host-pathogen interaction and the close links between bacterial infection and biological response of bone cells to microorganisms and their environment warrant to be explored.

• Study Type: Observational
• Enrollment (Anticipated): 20

Contacts and Locations

• Study Contact: Name: Martine COHEN-SOLAL, MD, PhD; Phone Number: +33(0)1 49 95 63 58; Email: martine.cohen-solal@aphp.fr

Study Locations

• France
  • Paris, France, 75010
    • Hôpital Lariboisière
    • Contact: Anne-Claude CREMIEUX, Md, PhD; Phone Number: +33(0) 1 42 49 40 15; Email: anne-claude.cremieux@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients eligible for lower limb revision surgery for infected or non-infected prosthesis. Primary care clinic.

Description

Inclusion Criteria:

• 18 years-old and older
• Patient eligible for lower limb revision surgery (revision surgery for infected or non-infected prosthesis)
• Patient affiliated to a social security system
• Oral consent to the research

Exclusion Criteria:

• NA

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
septic samples; patients undergoing revision surgery for prosthetic joint infection
aseptic samples; patients undergoing revision surgery for prosthetic replacement without infection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
markers of bone loss	Immunohistochemistry detection of Tartrate-resistant acid phosphatase cells (TRAP); cathepsin K; Matrix Metalloproteinase 9 (MMP9); sclerostin	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
markers of cellular activity in the bone microenvironment	immunohistochemistry detection of nuclear factor-activated T cells c1 (NFATc1); Matrix Metalloproteinase 9 (MMP9); Fibroblast growth factor 23 (FGF23)	12 months
immune-profiling of bone microenvironment	mapping lymphoid and myeloid cells by spectral flow cytometry assay	12 months
inflammatory mediators in the bone microenvironment	flow cytometry quantification of cytokine producing cells	12 months
differentiation between osteoclasts from mononuclear phagocytes	enzyme-linked immunosorbent (ELISA) and/or flow cytometry assays using specific antibodies	12 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Martine COHEN-SOLAL, MD, PhD, Assistance Publique - Hopitaux de Paris

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2022
• Primary Completion (Anticipated): October 1, 2022
• Study Completion (Anticipated): October 1, 2022

Study Registration Dates

• First Submitted: June 10, 2022
• First Submitted That Met QC Criteria: September 20, 2022
• First Posted (Actual): September 22, 2022

Study Record Updates

• Last Update Posted (Actual): September 22, 2022
• Last Update Submitted That Met QC Criteria: September 20, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: immune system; Staphylococcus; prosthetic joint infection; osteoblast; microenvironment; prosthesis loosening
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Joint Diseases; Musculoskeletal Diseases; Arthritis; Infections; Communicable Diseases; Arthritis, Infectious
• Other Study ID Numbers: APHP220417

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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