Network Medicine Approaches to Classify Heart Failure With PReserved Ejection Fraction by Signatures of DNA Methylation and Point-of-carE Risk calculaTors (PRESMET)

Atrial Fibrillation Clinical Trial

— PRESMET  

Official title:

Network Medicine Approaches to Classify Patients Suffering Heart Failure in Relation to Left Ventricle Ejection Fraction (HFpEF, HFmrEF, HFrEF) by Circulating CD4+ T Cell-derived DNA Methylation Signatures, Clinical Data, and Point-of-care Risk Calculators

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05475028
• Other study ID #: UniCampania
• Status: Completed
• Start date: September 14, 2021
• Est. completion date: June 14, 2022

Study information

• Verified date: July 2022
• Source: University of Campania "Luigi Vanvitelli"
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Heart failure (HF) is a syndrome, resulting from structural or functional impairment of ventricular filling or ejection of blood. Effective HF management depends on accurate and rapid diagnosis requiring assessment of symptoms and physical signs in combination with advanced and expensive imaging tools. However, several challenges arise from the traditional symptom-based diagnosis because co-morbidities of HF have similar presentations. This implies the need for a deeper knowledge of mechanistic links among genetic and epigenetic events governing the pathophysiology of HF leading to a novel molecular-based system to differentiate HF phenotypes. Now, it is emerging that the pathophysiology of HFpEF and HFrEF is different, it provides an opportunity to identify biomarker candidates that could aid in HF diagnosis and stratification between these two forms of the disease. The aim of PRESMET project is to perform liquid biopsy strategies to identify novel putative non-invasive epigenetic-sensitive biomarkers that could be used either alone or in combination with established diagnostic tests, such as natriuretic peptide, to help differentiate HFpEF from HFrEF. The Investigators will perform DNA methylation analysis on CD4+ T cells isolated from patients versus controls. Remarkably, big data generated from NGS tools will be analyzed by advanced network-oriented algorithms. Our results may provide a useful clinical roadmap in order to improve precision medicine and personalized therapy of HF.

Description:

The Investigators will perform the first Network Medicine approach to integrate the DNA methylome of circulating CD4+T cells and clinical parameters in patients with HFpEF and HFrEF.

Liquid biopsy strategies will be performed to isolate PBMCs and purificate CD4+ T cells. Successivelly, genomic DNA will be extracted on columns and will be send out for RRBS.

Network-oriented algorithms will be used to analyze DNA methylation signatures and to identify specific epigenetic changes in relation to left ventricle ejection fraction.

Network-oriented DNA methylation signatures will be integrated to the H2FPEF point-of-care calculator and, then, will be validated by the use of q-RT-PCR, WB, and ELISA.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: June 14, 2022
• Est. primary completion date: January 14, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• HFrEF (LVEF < 40%)

• HFpEF (LVEF > 50%)

Exclusion Criteria:

• Patients with HF with a history of a reduced LVEF = 40% (HFrEF) who recover LV function (LVEF = 50%)

• Chronic inflammatory diseases

• Cancer

Related Conditions & MeSH terms

• Atrial Fibrillation
• Heart Failure
• Heart Failure, Diastolic
• Heart Failure, Systolic
• Hypertension, Pulmonary
• Pulmonary Hypertension

Intervention

Other:
• RRBS
Reduced Representation Bisulfite Sequencing

Locations

Country	Name	City	State
Italy	University of Campania Luigi Vanvitelli	Naples

Sponsors (4)

Lead Sponsor	Collaborator
University of Campania "Luigi Vanvitelli"	Federico II University, Monaldi Hospital, University of Alabama at Birmingham

Country where clinical trial is conducted

Italy, 

References & Publications (1)

Napoli C, Benincasa G, Donatelli F, Ambrosio G. Precision medicine in distinct heart failure phenotypes: Focus on clinical epigenetics. Am Heart J. 2020 Jun;224:113-128. doi: 10.1016/j.ahj.2020.03.007. Epub 2020 Mar 12. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of differentially methylated regions (DMRs) in CD4+ T cells	The Investigators will identify the panel of DMRs able to distinguish HFpEF vs. HFrEF, HFpEF vs. healthy controls, and HFrEF vs. healthy controls.	3 months
Primary	Levels of differentially expressed genes in CD4+ T cells	The Investigators will measure the levels of gene expression of selected genes (qRT-PCR) in HFpEF vs. HFrEF, HFpEF vs. healthy controls, and HFrEF vs. healthy controls.	1 month