Role of Circulating MicroRNAs in Pathogenesis of Aneurysms of the Abdominal and Thoracic Aorta - Study "Micro AAA"

The objective of this study is to establish whether patients with aortic aneurysm, compared to general population, have higher levels of selected miRNAs and whether there is significant association between the level of miRNA in circulating blood and the size of the aortic aneurysm or the risk of its rupture.

Study Overview

• Status: Unknown
• Conditions: Aortic Aneurysm
• Intervention / Treatment: Genetic: PCR and sequencing

Detailed Description

Aneurysm of the abdominal and thoracic aorta represents a major cause of cardiovascular morbidity and mortality. The course of this condition can stay asymptomatic for long, and its first manifestation can be acute rupture of the aneurysm sac with life-threatening bleeding. Detection of patients at risk and their early treatment significantly reduce the percentage of this potentially lethal complications.

Aortic diseases are most often degenerative processes with a varying involvement of genetic predisposition. In literature, a substantial number of genes were proved to affect the metabolism of the vessel wall and to determine production of structural proteins, which were associated with the vascular pathologies. Pathophysiologic mechanisms of lesions of the aortic wall have not been completely understood. Among other, they include endothelial dysfunction, chronic inflammation of the vessel wall, apoptosis of smooth muscle cells and degradation of the extracellular matrix, resulting in the loss of integrity of layers of the vessel wall and decrease in its strength, which leads to dilation, rupture or dissection. Apart from mutations in genes coding the structural proteins of the vessel wall, many other potential biomarkers were proposed for early diagnosis of aortic aneurysm. These include microRNA (miRNA), one-fibre chains of non-coding ribonucleic acid which are several nucleotides long and are involved in the gene expression through the mechanism of inhibition of mRNA translation or increase in its degradation. Recently, association of levels of these miRNAs to presence and growth of aortic aneurysms has been described.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Jean Claude Lubanda, MD., Ph.D.; Phone Number: 00420224962692; Email: Jean-Claude.Lubanda@vfn.cz

Study Locations

• Czech Republic
  • Prague, Czech Republic, 12808
    • Recruiting
    • Charles University in Prague

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

• signed informed consent for participation to the study;
• age above 18 years;
• presence of untreated thoracic or abdominal aortic aneurysm (TAA or AAA);
• CT-verified diagnosis of AAA/TAA including measurement of the maximum diameter of the aneurysm.

Description

Inclusion Criteria:

study population:

• signed informed consent for participation to the study;
• age above 18 years;
• presence of untreated thoracic or abdominal aortic aneurysm (TAA or AAA);
• CT-verified diagnosis of AAA/TAA including measurement of the maximum diameter of the aneurysm.

control population:

• signed informed consent for participation in the study;
• age above 18 years;
• absence of a thoracic or abdominal aortic aneurysm (TAA or AAA).

Exclusion Criteria:

• life expectation above one year;
• history of myocardial infarction or unstable angina pectoris 1 month ago.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Study population; 100 Subjects followed in our department for the diagnosis of aortic aneurysm. On admission, the demographic data (see Appendix 1) will be recorded. Furthermore, within the routine clinically indicated laboratory samples, the levels of selected biochemical markers will be recorded (see Appendix 1). Follow up control laboratory will be performed one year, again within the routine samples.	Genetic: PCR and sequencing; Blood will be subsequently added into a test tube containing RNA solution of a stabilizer, necessary for preservation of the circulating miRNAs. Subsequently, centrifugation will be performed in a cooled centrifuge and the material thus processed will be kept for the subsequent isolation. The isolation of miRNA will be performed using the High Pure miRNA Isolation Kit (Roche, Basel, CHE) according to the manufacturer's standardized procedure. Presence and quality of the miRNA isolated will be spectrophotometrically confirmed using the NanoDrop device (ThermoScientific, Wilmington, DE, USA). By means of the data available in the on-line gene data basis, primers that are necessary for amplification of miRNA through the RT-PCR method using fluorescent dyes will be suggested.
Control population; The control population also includes 100 subjects in total. These will be chosen from aged and sex matched individuals seen in our clinic without disease of the aorta. All subjects included in trial must be at least 18 years old and must sign the informed consent to participation in the study. In the control population, also demographic data will be obtained and the levels of selected biochemical markers will be recorded within the routine clinically indicated laboratory samples.	Genetic: PCR and sequencing; Blood will be subsequently added into a test tube containing RNA solution of a stabilizer, necessary for preservation of the circulating miRNAs. Subsequently, centrifugation will be performed in a cooled centrifuge and the material thus processed will be kept for the subsequent isolation. The isolation of miRNA will be performed using the High Pure miRNA Isolation Kit (Roche, Basel, CHE) according to the manufacturer's standardized procedure. Presence and quality of the miRNA isolated will be spectrophotometrically confirmed using the NanoDrop device (ThermoScientific, Wilmington, DE, USA). By means of the data available in the on-line gene data basis, primers that are necessary for amplification of miRNA through the RT-PCR method using fluorescent dyes will be suggested.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in levels of circulating miRNAs	Difference in levels of circulating miRNAs (in ng/μl) in the population of patients with AAA/TAA compared to the control population without the aortic disease.	March 2017
Correlation between the level of the circulating miRNAs and the maximal diameter of the aneurysm sac.	Correlation between the level of the circulating miRNAs and the maximal diameter of the aneurysm sac.	March 2017

Collaborators and Investigators

• Sponsor: Charles University, Czech Republic

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2016
• Primary Completion (Anticipated): May 1, 2018
• Study Completion (Anticipated): June 1, 2019

Study Registration Dates

• First Submitted: March 20, 2017
• First Submitted That Met QC Criteria: March 20, 2017
• First Posted (Actual): March 27, 2017

Study Record Updates

• Last Update Posted (Actual): March 27, 2017
• Last Update Submitted That Met QC Criteria: March 20, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Aortic Diseases; Aneurysm; Aortic Aneurysm
• Other Study ID Numbers: Micro AAA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No