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

NCT03812627 | Completed

• 1 other identifier: APHP180539
• Study Type: interventional
• Target: 159
• Locations: 1 country
• Sites: 1

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.

Conditions

Biomarker; Systemic Inflammation

Keywords

Implantable medical devices; Biomarker; Systemic inflammation

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• 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

• 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 Outcomes (2)

• Trace elements dosing in liquids and tissues

  through study completion, an average of 2 years

• Comparison of concentrations of 40 analyzed trace elements

  through study completion, an average of 2 years

Study Arms (6)

Re-intervention of hip prosthesis made of ceramic or metal

EXPERIMENTAL

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)

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

Re-intervention of hip prosthesis of stainless steel ball

EXPERIMENTAL

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.

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

Re-intervention of knee prosthesis

EXPERIMENTAL

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.

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

Dead patients IMD holders autopsied

EXPERIMENTAL

Autopsy: 80 dead patients IMD holders will be autopsied.

Other: Autopsy

Dead patients non-IMD holders autopsied

ACTIVE COMPARATOR

Autopsy: dead patients non-IMD holders autopsied, 30 subjects in this arm.

Other: Autopsy

patients before first prosthesis surgery

ACTIVE COMPARATOR

Before the initial prosthesis surgery: 30 patients Blood, urine, hair, synovial fluid and peri-prosthetic tissue collections will be done

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

Interventions

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: 1. at the beginning of hospitalization: 10 ml of blood + 5 ml of urine; 2. 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

Re-intervention of hip prosthesis made of ceramic or metal; Re-intervention of hip prosthesis of stainless steel ball; Re-intervention of knee prosthesis; patients before first prosthesis surgery

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.

Dead patients IMD holders autopsied; Dead patients non-IMD holders autopsied

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Service de Chirurgie orthopédique, Hôpital Raymond Poincaré

Garches, Hauts-des-Seine, 92380, France

Location

MeSH Terms

Interventions

Blood Specimen Collection; Urination; Autopsy

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Urinary Tract Physiological Phenomena; Reproductive and Urinary Physiological Phenomena

Study Officials

• Jean-Claude Alvarez, MD, PhD

  Laboratoire de Pharmacologie-Toxicologie, Hôpital Raymond Poincaré, Garches

  PRINCIPAL INVESTIGATOR

• Thomas BAUER, MD, PhD

  Orthopédie et traumatologie, Hôpital Ambroise Paré, Boulogne-Billancourt

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2019
• First Posted: January 23, 2019
• Study Start: June 24, 2019
• Primary Completion: March 19, 2021
• Study Completion: March 19, 2021
• Last Updated: April 21, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)