Monocyte Activation in Preclinical Atherosclerosis

Completed

• Conditions: Atherosclerosis
• Interventions: Other: In vitro estimation of individual reactivity of monocytes

• Registration Number: NCT02126280
• Lead Sponsor: Institute for Atherosclerosis Research, Russia

Brief Summary

The study of proinflammatory and anti-inflammatory cytokines and chemokines expression profiles in human monocytes to identify new effective biomarkers that have the best diagnostic potential in asymptomatic atherosclerosis.

Detailed Description

This project is the first step in creating a method for assessing an individual activity of macrophages. The problems addressed in the project are socially significant because of the high incidence of life-threatening diseases and their effects in the population. The method of evaluation of monocyte-macrophages activity in human blood will be based on the analysis of expression of cytokines and chemokines - markers of inflammatory and anti-inflammatory activity of macrophages. The most informative panel of cytokines and chemokines obtained during the project can be further used to create effective diagnostic tests.

Study Timeline

• Study Start: 2012-11
• Status Verified: 2014-04
• Primary Completion: 2014-04
• Study Completion: 2014-04
• Study First Submitted: 2014-04-23
• Study First Submitted QC: 2014-04-28
• Last Update Submitted: 2014-04-28
• Study First Posted: 2014-04-30
• Last Update Posted: 2014-04-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 170

Inclusion Criteria

• men and women aged 40 to 74 years
• arterial normotension or mild arterial hypertension (systolic blood pressure <160 mm Hg, diastolic blood pressure <90 mm Hg)
• absence of chronic diseases demanding permanent drug administration (more than 2 month per year)

Exclusion Criteria

• personal history of transient ischemic attacks
• personal history of chronic diseases demanding permanent drug administration (more than 2 month per year)
• personal history of life-threatening diseases
• indications for surgical treatment of atherosclerotic lesions localized in the extracranial brachiocephalic system

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Subclinical atherosclerosis	In vitro estimation of individual reactivity of monocytes	In vitro estimation of individual reactivity of monocytes in study participants with asymptomatic atherosclerotic plaques found in carotid arteries by ultrasound examination
Healthy subjects	In vitro estimation of individual reactivity of monocytes	In vitro estimation of individual reactivity of monocytes in study participants without ultrasound signs of subclinical carotid atherosclerosis
Diffuse intimal thickening	In vitro estimation of individual reactivity of monocytes	In vitro estimation of individual reactivity of monocytes in study participants with diffuse intima-media thickening of carotid arteries found at ultrasound examination

Primary Outcome Measures

Name	Time	Method
Development and optimization of the method of monocyte-macrophage isolation.	up to 1 years	Technique for isolation/separation of monocytes with culture purity more than 95 % CD14-positive cells according to flow cytometry, the share of viable cells at least 98% by trypan blue vital staining, capable of producing TNFa at concentration of at least 50 pg/ml when stimulated with 100 ng/ml IFN-gamma, and CCL18 at concentration at least 30 pg/ml when stimulated with 10 ng/ml interleukin.

Secondary Outcome Measures

Name	Time	Method
Sample processing and parameter measurements.	up to 1 years	Creating a collection of samples of the culture medium during cell stimulation into pro-inflammatory or anti-inflammatory phenotype.; Definition of individual profiles of cell activation by the production of proinflammatory and anti-inflammatory cytokines and chemokines (C5a, IL-4, IL-32 alpha, CD40 ligand, IL-5, CXCL10, G-CSF, IL-6, CXCL11/I-TAC, GM-CSF , IL-8, CCL2, CXCL1, IL-10, MIF, CCL1, IL-12 p70, CCL3, ICAM-1, IL-13, CCL4, IFN-gamma, IL-16, CCL5, IL-1 alpha, IL -17, CXCL12, IL-1 beta, IL-17E, Serpin E1, IL-1ra, TNF-alpha, IL-2, IL-27, and TREM-1).; Database generation on individual reactivity of monocytes-macrophages from healthy donors, individuals predisposed to atherosclerosis, and patients with asymptomatic atherosclerosis.; Creating a collection of samples. Determination of concentrations of pro-inflammatory and anti-inflammatory markers.

Trial Locations

Locations (1)

Institute for Atherosclerosis Research; 🇷🇺 Moscow, Russian Federation