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Completed

NCT Number: NCT03812627

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

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.

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Key information

Conditions

Biomarker Systemic Inflammation

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Service de Chirurgie orthopédique, Hôpital Raymond Poincaré

Garches, Hauts-des-Seine, 92380, France

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Blood, urine, hair, synovial fluid and peri-prosthetic tissue collections

Other

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

Other

Dead patients will be autopsied: hair, urine, blood, peri-prosthetic tissue and viscera (liver, kidney, spleen, brain, heart, lung) sampling for each autopsy.

Primary outcomes

  1. Immunophenotyping of inflammatory cells activated in contact with trace element nanoparticles

    Time frame: 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.

  2. Identification of specific circulating proteins (biomarkers) of inflammation related to trace element release

    Time frame: 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

  3. Macroscopic characterization of tissue inflammation of autopsied patients

    Time frame: 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

  4. Microscopic characterization of tissue inflammation of autopsied patients

    Time frame: 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

Secondary outcomes

  1. Trace elements dosing in liquids and tissues

    Time frame: 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.

  2. Comparison of concentrations of 40 analyzed trace elements

    Time frame: through study completion, an average of 2 years

    Comparison of concentrations of 40 analyzed trace elements in different materials, depending on the groups.

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Registry information

Acronym: PROMETOX

Important dates

Study start
2019
Primary completion
2021
Study completion
2021
First posted
Jan 23, 2019
Registry last updated
Apr 21, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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