BiomarkerPROMETOXNCT03812627

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

A study testing Blood, urine, hair, synovial fluid and peri-prosthetic tissue collections and Autopsy in people with Biomarker and Systemic Inflammation, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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… Read more about this study

Who is it for?: Any age
Conditions the study is for: Biomarker, Systemic Inflammation
What is being tested?: Blood, urine, hair, synovial fluid and peri-prosthetic tissue collections and Autopsy
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 159 participants
Where: 1 siteFrance
Study dates: 24 Jun 2019to 19 Mar 2021
Phase: Interventional
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Any age
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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.

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

France1 site

Service de Chirurgie orthopédique, Hôpital Raymond Poincaré
Garches, Hauts-des-Seine, 92380

Other trials in France

About this study

Read the 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
Being tested: Blood, urine, hair, synovial fluid and peri-prosthetic tissue collections, Autopsy
Keywords: Implantable medical devices, Biomarker, Systemic inflammation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT03812627
Study group	Role	What they receive
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) Receives: 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. Receives: 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. Receives: 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. Receives: Other: Autopsy
Dead patients non-IMD holders autopsied	Active comparator	Autopsy: dead patients non-IMD holders autopsied, 30 subjects in this arm. Receives: 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 Receives: Other: Blood, urine, hair, synovial fluid and peri-prosthetic tissue collections

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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
Measured: 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
Measured: 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
Measured: through study completion, an average of 2 years

Secondary outcomes (2)

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.
Measured: through study completion, an average of 2 years
Comparison of concentrations of 40 analyzed trace elements
Comparison of concentrations of 40 analyzed trace elements in different materials, depending on the groups.
Measured: through study completion, an average of 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

24 Jun 201919 Mar 2021

First posted23 Jan 2019
Study start24 Jun 2019
Primary completion19 Mar 2021
Study completion19 Mar 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for BiomarkerStudies of the same condition, open and under way.
More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Other
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 159 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03812627
Sponsor's protocol ID: APHP180539
Acronym: PROMETOX
Status last verified: Apr 2022
First submitted: 11 Jan 2019
Last updated: 21 Apr 2022
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 21 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Study of Systemic Impact of Trace Elements Release by Implantable Medical Devices. Identification of Biomarkers of Systemic Inflammation
ClinicalTrials.gov ID: NCT03812627
Acronym / sponsor ID: PROMETOX / APHP180539
Conditions: Biomarker, Systemic Inflammation
Keywords: Implantable medical devices, Biomarker, Systemic inflammation
Study type: Interventional
Recruitment status: Completed
Enrolment: 159 participants (actual)
Lead sponsor: Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
Study start: 24 Jun 2019 (actual)
Primary completion: 19 Mar 2021 (actual)
Study completion: 19 Mar 2021 (actual)
First posted: 23 Jan 2019 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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 design

Primary purpose: Other
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 6

Arm	Type	Receives
Re-intervention of hip prosthesis made of ceramic or metal	Experimental	Other: Blood, urine, hair, synovial fluid and peri-prosthetic tissue collectionsRe-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	Experimental	Other: Blood, urine, hair, synovial fluid and peri-prosthetic tissue collectionsRe-intervention surgery: blood, urine, hair, synovial fluid and peri-prosthetic tissue collections. 50 patients for re-intervention of hip prosthesis of stainless steel ball.
Re-intervention of knee prosthesis	Experimental	Other: Blood, urine, hair, synovial fluid and peri-prosthetic tissue collectionsRe-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	Experimental	Other: AutopsyAutopsy: 80 dead patients IMD holders will be autopsied.
Dead patients non-IMD holders autopsied	Active comparator	Other: AutopsyAutopsy: dead patients non-IMD holders autopsied, 30 subjects in this arm.
patients before first prosthesis surgery	Active comparator	Other: Blood, urine, hair, synovial fluid and peri-prosthetic tissue collectionsBefore the initial prosthesis surgery: 30 patients Blood, urine, hair, synovial fluid and peri-prosthetic tissue collections will be done

Who may qualify

Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (3 listed)

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.

Key exclusion criteria (3 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Blood, urine, hair, synovial fluid and peri-prosthetic tissue collectionsAll 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	Other	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
AutopsyDead patients will be autopsied: hair, urine, blood, peri-prosthetic tissue and viscera (liver, kidney, spleen, brain, heart, lung) sampling for each autopsy.	Other	Dead patients IMD holders autopsied, Dead patients non-IMD holders autopsied

Primary outcome

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.
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
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
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

2 secondary outcomes

Trace elements dosing in liquids and tissues
Time frame: through study completion, an average of 2 years
Comparison of concentrations of 40 analyzed trace elements
Time frame: through study completion, an average of 2 years

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2022.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Jean-Claude Alvarez, MD, PhD principal investigator

Laboratoire de Pharmacologie-Toxicologie, Hôpital Raymond Poincaré, Garches

Thomas BAUER, MD, PhD study director

Orthopédie et traumatologie, Hôpital Ambroise Paré, Boulogne-Billancourt

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Immunophenotyping of inflammatory cells activated in contact with trace element nanoparticles (time frame: through study completion, an average of 2 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03812627.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2022.