Heart Failure, DiastolicPRESMETNCT05475028
Network Medicine Approaches to Classify Heart Failure With PReserved Ejection Fraction by Signatures of DNA Methylation and Point-of-carE Risk calculaTors (PRESMET)
An observational study of Heart Failure, Diastolic and Heart Failure, Systolic, run by University of Campania Luigi Vanvitelli at 1 site in Italy.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure, Diastolic, Heart Failure, Systolic, Pulmonary Hypertension
- What is being tested?
- RRBS
- How many people
- 60 participants
- Where
- 1 siteItaly
- Study dates
- 14 Sep 2021to 14 Jun 2022
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Our study population will be composed by: * N=20 HFpEF (LVEF > 50%) * N=20 HFrEF (LVEF < 40%) * N=20 healthy subjects
Who may be able to join
- HFrEF (LVEF < 40%)
- HFpEF (LVEF > 50%)
Who cannot join
- Patients with HF with a history of a reduced LVEF ≤ 40% (HFrEF) who recover LV function (LVEF ≥ 50%)
- Chronic inflammatory diseases
- Cancer
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the detailed 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.
- Conditions
- Heart Failure, Diastolic, Heart Failure, Systolic, Pulmonary Hypertension, Atrial Fibrillation
- Being tested
- RRBS
- Keywords
- HFpEF, Interactome, CD4+ T cells, HFrEF, Liquid biopsy, Network Medicine
- Medical subject headings
- Heart Failure, Diastolic, Heart Failure, Systolic, Hypertension, Pulmonary, Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RRBSOther
Reduced Representation Bisulfite Sequencing
| Study group | Role | What they receive |
|---|---|---|
| HFpEF | We will recruit HFpEF (LVEF > 50%) Receives: Other: RRBS | |
| HFrEF | We will recruit HFrEF (LVEF < 40%) Receives: Other: RRBS | |
| Healthy controls | We will recruit volunteer blood donors Receives: Other: RRBS |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 months
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.
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2022
- Study start14 Sep 2021
- Primary completion14 Jan 2022
- Study completion14 Jun 2022
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 Heart Failure, DiastolicStudies 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
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Campania Luigi Vanvitelli
- Sponsor type
- University, hospital or other
- Collaborators
- Monaldi Hospital, Federico II University, University of Alabama at Birmingham
- Responsible party
- Principal investigator, Giuditta Benincasa, University of Campania Luigi Vanvitelli
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05475028
- Sponsor's protocol ID
- UniCampania
- Acronym
- PRESMET
- Status last verified
- Jul 2022
- First submitted
- 21 Jul 2022
- Last updated
- 26 Jul 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 32361531
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05475028
- Acronym / sponsor ID
- PRESMET / UniCampania
- Conditions
- Heart Failure, Diastolic, Heart Failure, Systolic, Pulmonary Hypertension, Atrial Fibrillation
- Keywords
- HFpEF, Interactome, CD4+ T cells, HFrEF, Liquid biopsy, Network Medicine
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- University of Campania Luigi VanvitelliUniversity, hospital or other
- Collaborators
- Monaldi Hospital, Federico II University, University of Alabama at Birmingham
- Study start
- 14 Sep 2021 (actual)
- Primary completion
- 14 Jan 2022 (actual)
- Study completion
- 14 Jun 2022 (actual)
- First posted
- 26 Jul 2022 (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.
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.
Detailed 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.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| HFpEF | – | Other: RRBSWe will recruit HFpEF (LVEF > 50%) |
| HFrEF | – | Other: RRBSWe will recruit HFrEF (LVEF < 40%) |
| Healthy controls | – | Other: RRBSWe will recruit volunteer blood donors |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Our study population will be composed by: * N=20 HFpEF (LVEF > 50%) * N=20 HFrEF (LVEF < 40%) * N=20 healthy subjects
Key inclusion criteria (2 listed)
- HFrEF (LVEF < 40%)
- HFpEF (LVEF > 50%)
Key exclusion criteria (3 listed)
- Patients with HF with a history of a reduced LVEF ≤ 40% (HFrEF) who recover LV function (LVEF ≥ 50%)
- Chronic inflammatory diseases
- Cancer
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RRBSReduced Representation Bisulfite Sequencing | Other | HFpEF, HFrEF, Healthy controls |
Primary outcome
Percentage of differentially methylated regions (DMRs) in CD4+ T cells
Time frame: 3 months
The Investigators will identify the panel of DMRs able to distinguish HFpEF vs. HFrEF, HFpEF vs. healthy controls, and HFrEF vs. healthy controls.
Levels of differentially expressed genes in CD4+ T cells
Time frame: 1 month
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.
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 26 Jul 2022.
- Results publication: PubMed 32361531Napoli 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.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
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 Heart Failure, Diastolic and Heart Failure, Systolic, 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 2 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 26 Jul 2022. 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?
Percentage of differentially methylated regions (DMRs) in CD4+ T cells (time frame: 3 months). The study lists 2 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 NCT05475028, 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 26 Jul 2022.