Study of Systemic Impact of Trace Elements Release by Implantable Medical Devices. Identification of Biomarkers of Systemic Inflammation
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 159
- 试验地点
- 2
- 主要终点
- Macroscopic characterization of tissue inflammation of autopsied patients
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •Infection caused by prosthesis resumption;
- •Professional exposure to metals;
- •Patient under guardianship.
结局指标
主要结局
Macroscopic characterization of tissue inflammation of autopsied patients
时间窗: 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
时间窗: 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
Immunophenotyping of inflammatory cells activated in contact with trace element nanoparticles
时间窗: 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
时间窗: 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
次要结局
- 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)