Monocyte Activation in Preclinical Atherosclerosis (MAPA)

Cross-sectional Clinical Study of the Individual Profile of Activation of Circulating Blood Monocytes in Subjects With Preclinical Atherosclerosis.

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.

Study Overview

Status

Completed

Conditions

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 Type

Observational

Enrollment (Actual)

170

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Moscow, Russian Federation, 121609
        • Institute for Atherosclerosis Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 79 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

The inclusion of healthy individuals, of apparently healthy persons with a predisposition to atherosclerosis, and subjects with subclinical atherosclerosis, according to the results of ultrasonographic examination of carotids, to achieve 80% statistical power (up to 50 study participants per group).

Conducting experiments on obtaining the individual cultures of blood monocytes and stimulation of cells by proinflammatory and anti-inflammatory stimuli

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Development and optimization of the method of monocyte-macrophage isolation.
Time Frame: 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.
up to 1 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sample processing and parameter measurements.
Time Frame: 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.

up to 1 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Alexander N Orekhov, PhD, DSc, Institute for Atherosclerosis Research

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2012

Primary Completion (Actual)

April 1, 2014

Study Completion (Actual)

April 1, 2014

Study Registration Dates

First Submitted

April 23, 2014

First Submitted That Met QC Criteria

April 28, 2014

First Posted (Estimate)

April 30, 2014

Study Record Updates

Last Update Posted (Estimate)

April 30, 2014

Last Update Submitted That Met QC Criteria

April 28, 2014

Last Verified

April 1, 2014

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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