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

NCT ID: NCT03812627

Last Updated: 2022-04-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 159 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-24
• Study Completion Date: 2021-03-19

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.

Conditions

Biomarker; Systemic Inflammation

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Re-intervention of hip prosthesis made of ceramic or metal

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)

Group Type: EXPERIMENTAL

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

Intervention Type: 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 of stainless steel ball

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.

Group Type: EXPERIMENTAL

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

Intervention Type: 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 knee prosthesis

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.

Group Type: EXPERIMENTAL

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

Intervention Type: 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

Dead patients IMD holders autopsied

Autopsy: 80 dead patients IMD holders will be autopsied.

Group Type: EXPERIMENTAL

Autopsy

Intervention Type: 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 non-IMD holders autopsied

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

Group Type: ACTIVE_COMPARATOR

Autopsy

Intervention Type: OTHER

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

patients before first prosthesis surgery

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

Group Type: ACTIVE_COMPARATOR

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

Intervention Type: 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

Interventions

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:

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

Intervention Type: OTHER

Autopsy

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

Intervention Type: OTHER

Eligibility Criteria

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.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean-Claude Alvarez, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Laboratoire de Pharmacologie-Toxicologie, Hôpital Raymond Poincaré, Garches

Thomas BAUER, MD, PhD

Role: STUDY_DIRECTOR

Orthopédie et traumatologie, Hôpital Ambroise Paré, Boulogne-Billancourt

Locations

Service de Chirurgie orthopédique, Hôpital Raymond Poincaré

Garches, Hauts-des-Seine, France

Countries

France

Other Identifiers

APHP180539

Identifier Type: -

Identifier Source: org_study_id