Pulmonary Arterial HypertensionCLEOPAHTRANCT04282434
DNA Methylation Dynamics Underlying Arterial Remodeling in PAH Patients: CLEOPAHTRA Clinical Trial
An observational study of Pulmonary Arterial Hypertension and Pulmonary Arterial Remodeling, run by University of Campania Luigi Vanvitelli at 1 site in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Pulmonary Arterial Hypertension, Pulmonary Arterial Remodeling
- How many people
- 30 participants
- Where
- 1 siteItaly
- Study dates
- 14 Jun 2019to 14 Oct 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Adult, Older adult
Study population: 30 PAH patients (familial and idiopathic) vs 30 sex and age-matched subjects.
Who may be able to join
- 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)
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: CLinical Epigenetic-sensitive trajectOries Underlying Pulmonary Arterial Hypertension and neTwoRk Analysis (CLEOPAHTRA)
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.
Read the 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.
- Keywords
- Adaptive immunity, DNA methylome, RNA-sequencing, Network analysis
- Medical subject headings
- Pulmonary Arterial Hypertension, Vascular Remodeling
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of differentially methylated regions in CD04 and CD08 T cells
Reduced Representation Bisulfite Sequencing
Measured: 3 Months
Identification of differentially expressed genes in lung tissue biopsies
Chip Microarray
Measured: 5 Months
Bioinformatic analysis
Measured: 8 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2020
- Study start14 Jun 2019
- Primary completion14 Jun 2020
- Study completion14 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Campania Luigi Vanvitelli
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Giuditta Benincasa, University of Campania Luigi Vanvitelli
- Investigators
- Giuditta Benincasa, BiolD, MSc, Principal investigator, University of Campania "L. Vanvitelli"
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04282434
- Sponsor's protocol ID
- CLEOPAHTRA
- Other IDs
- PRIN2017F8ZB89
- Acronym
- CLEOPAHTRA
- Status last verified
- Jul 2021
- First submitted
- 21 Feb 2020
- Last updated
- 14 Jul 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Napoli C, Benincasa G, Loscalzo J. Epigenetic Inheritance Underlying Pulmonary Arterial Hypertension. Arterioscler Thromb Vasc Biol. 2019 Apr;39(4):653-664. doi: 10.1161/ATVBAHA.118.312262.
PubMed 30727752
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CLinical Epigenetic-sensitive trajectOries Underlying Pulmonary Arterial Hypertension and neTwoRk Analysis (CLEOPAHTRA)
- ClinicalTrials.gov ID
- NCT04282434
- Acronym / sponsor ID
- CLEOPAHTRA / CLEOPAHTRA
- Keywords
- Adaptive immunity, DNA methylome, RNA-sequencing, Network analysis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of Campania Luigi VanvitelliUniversity, hospital or other
- Study start
- 14 Jun 2019 (actual)
- Primary completion
- 14 Jun 2020 (actual)
- Study completion
- 14 Oct 2020 (actual)
- First posted
- 24 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Observational model
- Case-control
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- 30 PAH patients (familial and idiopathic) vs 30 sex and age-matched subjects.
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Identification of differentially methylated regions in CD04 and CD08 T cells
Time frame: 3 Months
Reduced Representation Bisulfite Sequencing
Identification of differentially expressed genes in lung tissue biopsies
Time frame: 5 Months
Chip Microarray
Bioinformatic analysis
Time frame: 8 Months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2021.
- Results publication: PubMed 30727752Napoli C, Benincasa G, Loscalzo J. Epigenetic Inheritance Underlying Pulmonary Arterial Hypertension. Arterioscler Thromb Vasc Biol. 2019 Apr;39(4):653-664. doi: 10.1161/ATVBAHA.118.312262.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Giuditta Benincasa, BiolD, MSc principal investigator
University of Campania "L. Vanvitelli"
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pulmonary Arterial Hypertension and Pulmonary Arterial Remodeling, run by University of Campania Luigi Vanvitelli at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification of differentially methylated regions in CD04 and CD08 T cells (time frame: 3 Months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04282434, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2021.