DNA Methylation Dynamics Underlying Arterial Remodeling in PAH Patients: CLEOPAHTRA Clinical Trial

Sponsor

University of Campania "Luigi Vanvitelli" (Other)

Overall Status

Completed

CT.gov ID

NCT04282434

Collaborator

(none)

Enrollment

Location

Actual Duration (Months)

1.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To identify epigenetic-sensitive modifications and novel biomarkers linked to pathogenesis of pulmonary arterial hypertension (PAH), we will perform the first study analyzing differentially-methylated regions (DMRs) in circulating T cells (CD04+ and CD08+) isolated from peripheral blood of patients undergoing right heart catheterization. Moreover, we will perform RNA deep sequencing on lung tissue biopsies to validate if DNA methylation signatures in circulating T cells could reflect perturbations of gene expression in lung tissues.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Arterial Hypertension Pulmonary Arterial Remodeling

Detailed Description

Pulmonary arterial hypertension (PAH) is characterized by remodeling of pulmonary arteries caused by an inbalance of proliferation/apoptosis rate within the vascular wall. This pathological phenotype seems to be triggered by different environmental stress and injury events such as increased inflammation, DNA damage, and epigenetic deregulation. Many immune cells are increased in PAH, such as T and B lymphocytes. Remarkably, T cells are essential players of adaptive immunity and may be relevant initiators ("initial hit") of vascular remodelling. We will perform the first multi-omics study to: 1) investigate DNA methylome of circulating T cells isolated from peripheral blood of PAH patients, 2) detect transcriptomic profiles of lung tissues, 3) to assess if DNA methylation of distinct genomic regions in circulating T cells could reflect modifications of lung gene expression programs.

Study Design

Study Type:

Observational

Actual Enrollment :

30 participants

Observational Model:

Case-Control

Time Perspective:

Cross-Sectional

Official Title:

CLinical Epigenetic-sensitive trajectOries Underlying Pulmonary Arterial Hypertension and neTwoRk Analysis (CLEOPAHTRA)

Actual Study Start Date :

Jun 14, 2019

Actual Primary Completion Date :

Jun 14, 2020

Actual Study Completion Date :

Oct 14, 2020

Outcome Measures

Primary Outcome Measures

Identification of differentially methylated regions in CD04 and CD08 T cells [3 Months]
Reduced Representation Bisulfite Sequencing
Identification of differentially expressed genes in lung tissue biopsies [5 Months]
Chip Microarray
Bioinformatic analysis [8 Months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Inclusion Criteria:

Newly diagnosed patients with World Health Organization (WHO) Group I PAH.
≥ 18 years
Documentation of the following hemodynamic parameters by right heart catheterization, performed at time of study enrolment:
Mean pulmonary arterial pressure (mPAP) > 25 mmHg at rest or mPAP > 30 mm Hg with exercise.
Pulmonary arterial wedge pressure (PAWP) ≤ 15 mm Hg.
Pulmonary vascular resistance (PVR) ≥ 240 dynes.sec.cm-5 (e.g., ≥ 3.0 Wood units)

Exclusion Criteria:

Patients who meet the criteria for inclusion into WHO Groups II, III, IV or V.
Do not meet the required hemodynamic criteria for entry into the study.
Patients with known history of cancer, malignancy disorders, active infections, and chronic or immune-mediated diseases.