Study of Systemic Impact of Trace Elements Release by Implantable Medical Devices. Identification of Biomarkers of Systemic Inflammation

Not Applicable

Completed

• Conditions: Biomarker; Systemic Inflammation
• Interventions: Other: Blood, urine, hair, synovial fluid and peri-prosthetic tissue collections; Other: Autopsy

• Registration Number: NCT03812627
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

The main objective of this study is to evaluate the systemic impact of salting out of trace elements (TE) by metallic and nonmetallic implantable medical devices (IMD) and in particular the immune response of the organism to these trace elements and of their target organs, and to identify circulating protein biomarkers which might indicate an evolution of inflammation caused by an IMD.

Detailed Description

As secondary objectives, the study aims:

* to establish the norms of concentrations of free TE and nanoparticles for some forty of elements (in particular Chrome, Cobalt, Nickel, Titanium, Tantalum, Zirconium, Tungsten, Gold, Silver, Mercury, Molybdenum, Strontium ...) in different materials (blood, urine, hair and the viscera), with non-IMD holder subjects, before and after mineralization of these materials (dead patients and autopsied non-IMD holder subjects and subjects before placement of IMD.

* to evaluate the distribution of concentrations of metals in the same materials and in peri-prothetic environment with IMD holder subjects (dead autopsied patients), more often with no inflammatory sign, with possibility of some probably inflammatory IMD.

* to evaluate the parameters of distributions of concentrations of metals in same materials (with the exception of the viscera) with living IMD holder patients, with inflammatory reaction (during revision surgery).

* to define the most suitable material (accessibility, concentrations, absence of contamination) for follow-up and evolution of inflammation in order to determinate norms of studied metals concentration.

* to determinate proportion between different forms of circulation: particulate form (analysis after full mineralization) or free form (analysis without mineralization, permitting measurement of free forms), trace elements in organism.

Study Timeline

• Study First Submitted: 2019-01-11
• Study First Submitted QC: 2019-01-22
• Study First Posted: 2019-01-23
• Study Start: 2019-06-24
• Primary Completion: 2021-03-19
• Study Completion: 2021-03-19
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-20
• Last Update Posted: 2022-04-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 159

Inclusion Criteria

• Inpatient subjects for re-intervention of: hip prosthesis made by ceramic-on-ceramic or metal-on-metal, hip prosthesis made by stainless steel ball and knee prosthesis made by polyethylene-on-metal;
• Autopsied patients with and without IMD;
• Covered by a health insurance.

Exclusion Criteria

• Infection caused by prosthesis resumption;
• Professional exposure to metals;
• Patient under guardianship.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Re-intervention of knee prosthesis	Blood, urine, hair, synovial fluid and peri-prosthetic tissue collections	Re-intervention surgery: blood, urine, hair, synovial fluid and peri-prosthetic tissue collections. 50 inpatient subjects for re-intervention of knee prosthesis polyethylene-on-metal.
Dead patients IMD holders autopsied	Autopsy	Autopsy: 80 dead patients IMD holders will be autopsied.
patients before first prosthesis surgery	Blood, urine, hair, synovial fluid and peri-prosthetic tissue collections	Before the initial prosthesis surgery: 30 patients Blood, urine, hair, synovial fluid and peri-prosthetic tissue collections will be done
Dead patients non-IMD holders autopsied	Autopsy	Autopsy: dead patients non-IMD holders autopsied, 30 subjects in this arm.
Re-intervention of hip prosthesis made of ceramic or metal	Blood, urine, hair, synovial fluid and peri-prosthetic tissue collections	Re-intervention surgery: blood, urine, hair, synovial fluid and peri-prosthetic tissue collections. 50 patients for re-intervention of hip prosthesis with friction couples of: ceramic-on-ceramic or metal-on-metal (25 patients by group)
Re-intervention of hip prosthesis of stainless steel ball	Blood, urine, hair, synovial fluid and peri-prosthetic tissue collections	Re-intervention surgery: blood, urine, hair, synovial fluid and peri-prosthetic tissue collections. 50 patients for re-intervention of hip prosthesis of stainless steel ball.

Primary Outcome Measures

Name	Time	Method
Macroscopic characterization of tissue inflammation of autopsied patients	through study completion, an average of 2 years	Demonstration of systemic inflammation induced by the trace elements existing in IMD with blood and tissue criteria: - 3/ A macroscopic study of organs to determine the possible presence of tumor foci
Microscopic characterization of tissue inflammation of autopsied patients	through study completion, an average of 2 years	Demonstration of systemic inflammation induced by the trace elements existing in IMD with blood and tissue criteria: - 4/ Cytopathological analysis on slides, after sampling, fixation, inclusion and staining with hematoxylin-eosin-saffron to evaluate semi-quantitatively the type of inflammation (chronic if mononuclear cells or acute if neutrophils) and degree according to the number of inflammatory cells
Immunophenotyping of inflammatory cells activated in contact with trace element nanoparticles	through study completion, an average of 2 years	Demonstration of systemic inflammation induced by the trace elements existing in IMD with blood and tissue criteria: 1/ A measure by flow cytometry to identify hyperactivated circulating mononuclear cells (macrophages, dendritic cells, T and B lymphocytes), in contact with trace element nanoparticles and thus, to highlight an immunophenotype of this inflammation.
Identification of specific circulating proteins (biomarkers) of inflammation related to trace element release	through study completion, an average of 2 years	Demonstration of systemic inflammation induced by the trace elements existing in IMD with blood and tissue criteria: 2/ A measure by multiplex LuminexTM (Bio-plex ProTM human inflammation panel, Bio-rad) to identify specific circulating proteins such as TNF, IFN, cytokines, chemokines, metalloproteins, related to activation of the cells of inflammation throughout release of particles and salting out of trace elements by IMD

Secondary Outcome Measures

Name	Time	Method
Trace elements dosing in liquids and tissues	through study completion, an average of 2 years	Trace elements dosing in liquids and tissue by high resolution ICP mass spectrometry in studied sub-population (autopsied IMD holder and non-holder dead subjects, IMD holder living patients with inflammatory reaction and will undergo re-intervention) and in each analyzed material in non-mineralized form, in order to determinate concentrations of free trace elements and after full mineralization to determinate the concentrations of trace elements in nanoparticle form.
Comparison of concentrations of 40 analyzed trace elements	through study completion, an average of 2 years	Comparison of concentrations of 40 analyzed trace elements in different materials, depending on the groups.

Trial Locations

Locations (1)

Service de Chirurgie orthopédique, Hôpital Raymond Poincaré; 🇫🇷 Garches, Hauts-des-Seine, France