Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04296253 |
| Other study ID # |
SNP_1 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
March 15, 2019 |
| Est. completion date |
September 30, 2020 |
Study information
| Verified date |
October 2021 |
| Source |
Tomsk National Research Medical Center of the Russian Academy of Sciences |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The purpose of this study is to explore the serum levels of pro- and anti-inflammatory
biomarkers and angiogenic growth factors and SNP polymorphisms of the promoter regions of
their genes as well as to determine their role in the development of adverse cardiac
remodeling in patients with acute ST-segment elevation myocardial infarction.
Description:
The widespread introduction of modern methods of treatments of myocardial infarction in
routine clinical practice has lead not only to a decrease in mortality, but also to an
increase in the number of patients with chronic heart failure. It is known that inflammation
develops in myocardial infarction in response to cell damage, which is accompanied by
activation of the cells of the immune system and eventually with scarring. Chronic aseptic
inflammation is not only a universal biological reaction in response to necrosis of
cardiomyocytes, but the cellular molecular basis of post-infarction cardiac remodeling. At
the same time, the imbalance of pro- and anti-inflammatory mediators can have some negative
effects on the healing processes of the damaged myocardium and subsequent remodeling of the
heart. In adverse heart remodeling, elevated levels of proinflammatory cytokines (IL-1β,
IL-6, TNF-α, etc.) and reduced secretion of anti-inflammatory cytokines (IL-4, IL-10, etc.)
persist for a long time.
Recently, the endotoxin hypothesis of cytokine production has been of great interest among
scientists. Endotoxin is a molecule of the lipopolysaccharide (LPS) of the outer cell wall of
gram-negative bacteria. LPS is a powerful inducer of cytokine release, and chronic endotoxin
load is at least one of the reasons for the activation of the innate immune system. One of
the most important and unresolved problems in pathophysiology is the study of the nature of
the inflammatory response, or rather the cytokine response cascade, reparation and
neoangiogenesis developing in the myocardium in response to ischemic damage, as well as
genetically determined regulation of these processes. Factors determining the dual role of
cytokines in the development of adverse cardiac remodeling can be polymorphisms of their
genes, in particular, single nucleotide polymorphism of genes - SNP (single nucleotide
polymorphism) with replacement of one nucleotide by another. SNP in promoter regions regulate
the intensity of gene expression, different levels of secretion and function of interleukins,
growth factors, and, accordingly, their biological effects. Uncovering the mechanisms that
regulate the secretion of angiogenic growths factors, pro- and anti-inflammatory cytokines in
patients with AMI could potentially become the basis for developing new treatment tactics
based on modulating the immune response and neoangiogenesis in AMI by introducing into
ischemic tissues of cytokines or angiogenic growth factors in the form recombinant proteins
or as a part of genetic constructs to stimulate regeneration.
A total of 200 patients with acute primary myocardial infarction with ST segment elevation
will be recruited. Upon admission, all patients receive standard therapy, as recommended for
the treatment of myocardial infarction. Within 24 hours of admission, coronary angiography
and revascularization of the infarct-related artery are performed. On the days 1 and 7 of
hospitalization and on the day of discharge, blood will be taken to determine the dynamics of
serum concentrations of pro- and anti-inflammatory biomarkers, markers of myocardial
necrosis; gene polymorphisms will be studied; echocardiography will be performed to assess
the structural and functional characteristics of the heart after AMI. After 3 and 12 months,
patients undergo studies to dynamically assess the structural and functional state of the
heart.
