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

Biomarker Clinical Trial

— PROMETOX  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03812627
• Other study ID #: APHP180539
• Status: Completed
• Phase: N/A
• Start date: June 24, 2019
• Est. completion date: March 19, 2021

Study information

• Verified date: April 2022
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 159
• Est. completion date: March 19, 2021
• Est. primary completion date: March 19, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Biomarker
• Inflammation
• Systemic Inflammation

Intervention

Other:
• Blood, urine, hair, synovial fluid and peri-prosthetic tissue collections
All inpatient subjects: following samples will be collected during hospitalization: Twice blood and urine collections: at the beginning of hospitalization: 10 ml of blood + 5 ml of urine; at the end of hospitalization: 5 ml of blood + 5 ml of urine. Synovial fluid collection: 1 ml Peri-prosthetic tissue collection: about 1 cm3 Hair collection: a single hair of 0.5 cm diameter
• Autopsy
Dead patients will be autopsied: hair, urine, blood, peri-prosthetic tissue and viscera (liver, kidney, spleen, brain, heart, lung) sampling for each autopsy.

Locations

Country	Name	City	State
France	Service de Chirurgie orthopédique, Hôpital Raymond Poincaré	Garches	Hauts-des-Seine

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Immunophenotyping of inflammatory cells activated in contact with trace element nanoparticles	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.	through study completion, an average of 2 years
Primary	Identification of specific circulating proteins (biomarkers) of inflammation related to trace element release	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	through study completion, an average of 2 years
Primary	Macroscopic characterization of tissue inflammation of autopsied patients	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	through study completion, an average of 2 years
Primary	Microscopic characterization of tissue inflammation of autopsied patients	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	through study completion, an average of 2 years
Secondary	Trace elements dosing in liquids and tissues	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.	through study completion, an average of 2 years
Secondary	Comparison of concentrations of 40 analyzed trace elements	Comparison of concentrations of 40 analyzed trace elements in different materials, depending on the groups.	through study completion, an average of 2 years