Monocyte Activation in Preclinical Atherosclerosis

Atherosclerosis Clinical Trial

— MAPA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02126280
• Other study ID #: IAR-MAPA
• Status: Completed
• Phase: N/A
• First received: April 23, 2014
• Last updated: April 28, 2014
• Start date: November 2012
• Est. completion date: April 2014

Study information

• Verified date: April 2014
• Source: Institute for Atherosclerosis Research, Russia
• Contact: n/a
• Is FDA regulated: No
• Health authority: Russia: Ethics Committee
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 170
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 40 Years to 79 Years

Eligibility

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

Observational Model: Cohort, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Atherosclerosis

Intervention

Other:
• In vitro estimation of individual reactivity of monocytes
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.

Locations

Country	Name	City	State
Russian Federation	Institute for Atherosclerosis Research	Moscow

Sponsors (1)

Lead Sponsor	Collaborator
Institute for Atherosclerosis Research, Russia

Country where clinical trial is conducted

Russian Federation, 

References & Publications (2)

Gratchev A, Ovsiy I, Manousaridis I, Riabov V, Orekhov A, Kzhyshkowska J. Novel monocyte biomarkers of atherogenic conditions. Curr Pharm Des. 2013;19(33):5859-64. Review. — View Citation

Gratchev A, Sobenin I, Orekhov A, Kzhyshkowska J. Monocytes as a diagnostic marker of cardiovascular diseases. Immunobiology. 2012 May;217(5):476-82. doi: 10.1016/j.imbio.2012.01.008. Epub 2012 Jan 13. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Development and optimization of the method of monocyte-macrophage isolation.	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	Yes
Secondary	Sample processing and parameter measurements.	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	Yes