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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04282434
Recruitment Status : Recruiting
First Posted : February 24, 2020
Last Update Posted : March 4, 2020
Information provided by (Responsible Party):
Giuditta Benincasa, University of Campania "Luigi Vanvitelli"

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
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.

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Study Type : Observational
Estimated 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 : June 14, 2019
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : December 2021

Primary Outcome Measures :
  1. Identification of differentially methylated regions in CD04 and CD08 T cells [ Time Frame: 3 Months ]
    Reduced Representation Bisulfite Sequencing

  2. Identification of differentially expressed genes in lung tissue biopsies [ Time Frame: 5 Months ]
    Chip Microarray

  3. Bioinformatic analysis [ Time Frame: 8 Months ]

Biospecimen Retention:   Samples With DNA
Circulating T cells Lung tissue biopsy

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Sampling Method:   Probability Sample
Study Population
30 PAH patients (familial and idiopathic) vs 30 sex and age-matched subjects.

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 (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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04282434

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Contact: Giuditta Benincasa, BiolD. MSc +39 0815667916
Contact: Claudio Napoli, Professor

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Monaldi Hospital Recruiting
Naples, Italy
Contact: Giuditta Benincasa, BiolD, MSc         
Sponsors and Collaborators
University of Campania "Luigi Vanvitelli"
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Principal Investigator: Giuditta Benincasa, BiolD, MSc University of Campania "L. Vanvitelli"
Publications of Results:
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Responsible Party: Giuditta Benincasa, Principal Investigator Giuditta Benincasa, University of Campania "Luigi Vanvitelli" Identifier: NCT04282434    
Other Study ID Numbers: CLEOPAHTRA
PRIN2017F8ZB89 ( Other Grant/Funding Number: Italian Ministry of University and Research (MIUR) )
First Posted: February 24, 2020    Key Record Dates
Last Update Posted: March 4, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Giuditta Benincasa, University of Campania "Luigi Vanvitelli":
Adaptive immunity
DNA methylome
Network analysis
Additional relevant MeSH terms:
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Familial Primary Pulmonary Hypertension
Vascular Remodeling
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases
Pathological Conditions, Anatomical
Pathologic Processes