Risk Factors for Enhanced Inflammation to Arthroplasty Wear Particles: Analysis of Cytokine Production and Polymorphisms

Individual Risk Factors for Enhanced Inflammation to Arthroplasty Wear Particles: Analysis of Cytokine Polymorphisms and in Vitro Cytokine Production to Wear Particles (Ceramic, Metal, XPE)

Assessment of cytokine polymorphisms in 100 patients with aseptic complications to arthroplasty as compared to 100 symptom-free arthroplasty patients.

In selected patients additional in-vitro cytokine release assay with peripheral blood mononuclear cells (PBMC) stimulated with different wear particles.

Study Overview

• Status: Completed
• Conditions: Allergy; Implants

Detailed Description

A cytokine polymorphism analysis in 100 individuals with aseptic implant intolerance reaction (patients of the implant allergy special ambulance) and in 100 asymptomatic patients with implanted endoprostheses will be done. Furthermore, supplementary clinical data (such as type of implant, hospital stay, discomfort), questionnaire-based history and a clinical score (WOMAC score) are recorded. In the subgroup analysis in 10 patients of implant patients with complaints with special found cytokine polymorphisms and 10 implant patients without problems the cytokine response to particles in vitro will assessed.

Test parameters:

1. total collective:

   the DNA of cryopreserved blood sample will be isolated. By polymerase chain reaction, four different known polymorphisms will be analyzed, three IL-1B genes (IL-1B-3954 IL-1B-31, and IL-1B-511), and a IL-1ß receptor antagonist gene (IL -1-RN, intron 2 VNTR). Molecular analysis includes DNA isolation, polymerase chain reactions (PCR) and gel electrophoresis.

2. Subgroup analysis:

Peripheral blood cells will be isolated from 10 implant patients with complications and 10 symptom-free persons and stimulated in cell culture with control stimuli, the IL-1ß-inducer lipopolysaccharide (LPS) and ceramic particles (BIOLOX delta)*, CoCrMo particles and XPE-particles** cultured separately or in combination. The secretion of IL-1ß and selected proinflammatory cytokines will be measured. The methods include cell isolation by density centrifugation and analysis of cell culture supernatants by a multiplex cytokine measurement assay by flow cytometry.

* Supplied CeramTec

** Generated and processed by the Working Group of the cooperation partner Prof. R. Bader (University Hospital Rostock) in special carrier system for cell culture stimulation approach

• Study Type: Observational
• Enrollment (Actual): 195

Contacts and Locations

Study Locations

• Germany
  • Bavaria
    • Munich, Bavaria, Germany, 80337
      • Ludwig-Maximilians-University Munich, Dept. of Dermatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with arthroplasty:

A) without symptoms B) with aseptic complications

Description

Inclusion Criteria:

• arthroplasty
• over 18 years
• no infection

Exclusion Criteria:

• inability to consent
• malposition
• infection

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Patients; Patients with suspected arthroplasty intolerance
Controls; Patients with well tolerated arthroplasties

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Polymorphism frequency	Frequency of 4 different cytokine polymorphisms will be assessed in the 2 study groups.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cytokine production	Subgroup analysis: In vitro cytokine production of 20 patients with special polymorphism constellation will be analyzed after stimulation with particles.	1 year

Collaborators and Investigators

• Sponsor: Ludwig-Maximilians - University of Munich
• Collaborators: Technical University of Munich; University of Rostock
• Investigators: Principal Investigator: Peter Thomas, Prof. Dr., Ludwig-Maximilians - University of Munich

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): January 1, 2018
• Study Completion (Actual): February 22, 2019

Study Registration Dates

• First Submitted: December 23, 2013
• First Submitted That Met QC Criteria: October 7, 2014
• First Posted (Estimate): October 10, 2014

Study Record Updates

• Last Update Posted (Actual): February 27, 2019
• Last Update Submitted That Met QC Criteria: February 26, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: cytokine; allergy; implant; particle
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation
• Other Study ID Numbers: 230-12