Heart FailureBACE1AS-HFNCT06213493
Bace1as Role in Heart Failure (BACE1AS-HF)
An observational study of Heart Failure and Acute Coronary Syndrome, run by IRCCS Policlinico S. Donato at 1 site in Italy.
Trial summary
The objective of this project is 1) to explore the clinical relevance of BACE1-AS and BACE1 as therapeutic targets and 2) to evaluate their potentiality as biomarkers in ischemic heart failure (HF). Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Heart Failure, Acute Coronary Syndrome
- What is being tested?
- measurement of RNAs
- How many people
- 630 participants
- Where
- 1 siteItaly
- Study dates
- 12 Mar 2021to 30 Nov 2024
- 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
- Healthy volunteers accepted
- Adult, Older adult
Study population: 1. Left ventricular biopsies from patients with post-ischemic HF. Left ventricular tissue fragments from patients with post-ischemic HF undergoing to left ventricular reconstruction (SVR) will be used 2. Patients with acute coronary syndrome and left ventricular dysfunction 12 months after percutaneous angioplasty Control group will be represented by patients suffering from unstable angina. 3. Patients with chronic post-ischemic HF (recruitment at the Istituti Clinici Scientifici Maugeri Pavia ICS) All patients admitted with a diagnosis of chronic heart failure or an ischemic or "acute" basis due to exacerbation.
Who may be able to join
- left ventricular reconstruction surgery (SVR)
- ESVI >35 ml/m2
- EF<40%
- previous anterior transmural infarction
- age 40-75 years
- Age >18 years
Show all 12Show fewer
- Patients with ACS (first episode), defined according to the ESC 2017 guidelines [19]
- Informed consent to enrollment in the study
- All patients admitted to Rehabilitation Cardiology at the Cardiology Department of ICS Maugeri with a diagnosis of chronic heart failure on an ischemic or "acute" basis due to exacerbation of chronic heart failure due to previous ischemia and whose therapies have been optimized at the moment of enlistment.
- NYHA Class II-III at the time of enlistment;
- Age over 18 years;
- Informed consent signed at the time of enrollment in the study.
Who cannot join
- ESVI <35 ml/m2
- EF>40%
- Tempo from E unknown
- Pregnant women
- Patients with genetic diseases
- Patients suffering from malignant neoplasm
Show all 33Show fewer
- Subjects with collagenopathies
- Subjects undergoing chemo/radiotherapy
- Subjects undergoing prolonged steroid therapy
- Subjects with known active infectious diseases
- Subjects with positive serology for HIV, HBV (not vaccinated), HCV.
- Patients with ACS and left ventricular dysfunction 12 months after percutaneous angioplasty
- Severe heart valve disease or other conditions requiring cardiac surgery
- Previous cardiac surgery including coronary artery bypass grafting
- Total chronic occlusions
- Patients with known hypersensitivity or contraindication to any of the following drugs:
- heparin aspirin, clopidogrel, ticlopidine, sirolimus, everolimus.
- Any contraindication to implantation of drug-eluting stents (DES)
- Patients with previous documented myocardial infarction;
- LVEF <30% before PCI
- Patients in cardiogenic shock
- Patients with advanced STEMI (> 48 h from the onset of symptoms/Q waves on ECG) or undergoing fibrinolysis;
- Patients with known previous cardiomyopathy with LVEF < 40%
- Patients suffering from malignant neoplasms or systemic pathologies with a quoad vitam prognosis of less than 1 year;
- Patients suffering from known active infectious diseases;
- Patients who are unable to express valid informed consent at the time of enrollment
- Pregnant women
- Patients with chronic post-ischemic HF ( recruitment at the Istituti Clinici Scientifici Maugeri Pavia)
- Denial of informed consent;
- End-stage renal disease;
- Presence of ACS, stroke, transient ischemic attack, major cardiovascular surgery, percutaneous coronary angioplasty or carotid angioplasty in the previous 3 months;
- Patients undergoing cardiac transplantation or on the active list for cardiac transplantation or undergoing LVAD implantation;
- Presence of hemodynamically significant mitral or aortic valve disease except mitral insufficiency due to ventricular dilatation;
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Role of the BACE1-AS Long Noncoding RNA in Ischemic Heart Failure
The objective of this project is 1) to explore the clinical relevance of BACE1-AS and BACE1 as therapeutic targets and 2) to evaluate their potentiality as biomarkers in ischemic heart failure (HF).
The first aim will be studied by validating in left ventricle biopsies in patients with post-ischemic heart failure the transcriptome and DNA methylation status data obtained in cell lines where the expression of BACE1-AS has been modulated.
The investigation of BACE1-AS and BACE1 as biomarkers will be obtained by using peripheral blood mononuclear cells (PBMCs) from patients with acute coronary syndrome (ACS) treated with percutaneous angioplasty (PCI) procedure and undergoing to left ventricular remodeling. Furthermore, PBMCs from patients with chronic ischemic HF recruited from the Istituti Clinici Scientifici Maugeri Pavia will be also used. From the data obtained from these patients and from non-decompensated subjects, the levels of BACE1-AS and BACE1 in the blood will be measured and correlated with each other and with β-amyloid levels (βA), as well as with clinically relevant parameters.
Read the detailed description
1.1) Validation of transcriptomic data obtained in vitro: The transcriptome of the AC16 cardiomyocyte cell line in which the expression of BACE1-AS was induced by lentivirus vectors will be analyzed, thus identifying the transcripts specifically modulated by BACE1-AS. The data obtained in vitro will be validated by analyzing the RNAs extracted from 20 HF patients and 20 controls. These RNA samples are already available thanks to the RNA_HF_AS project "Study of the transcriptome in heart failure and aortic stenosis" (San Raffaele Hospital - Milan, Ethics Committee CE 85/int/2016).
1.2) Validation of epigenetic data: The effect of BACE1-AS on the state of DNA methylation will be studied in the AC16 cardiomyocyte cell line. In over-expressing BACE1-AS cells, DNA hypomethylation will be evaluated by MS-HRM and pyrosequencing studies of bisulfite-modified genomic DNA of 69 enhancer sequences identified by us as candidates in preliminary studies. The data thus obtained will be validated in 20 cardiac biopsies from patients with post-ischemic HF and in 20 controls. Left ventricular biopsies will be taken after obtaining informed consent from 20 patients suffering from non-terminal dilated cardiomyopathy (DCM) undergoing left ventricular reconstruction (SVR) surgery at the San Donato Policlinico. A sufficient number of samples with these characteristics have already been obtained from IRCCS Policlinico San Donato as part of the RNA_HF_AS project (San Raffaele Hospital - Milan, Ethics Committee CE 85/int/2016). and not completely used for the study.
1.3) Study of the expression levels of BACE1-AS, BACE1 in PBMC of patients with ischemic cardiomyopathy.
The expression levels of BACE1 and BACE1-AS will be measured in PBMCs from the following groups:
Group 1:
130 ACS patients with left ventricular systolic dysfunction (left ventricular ejection fraction (LVEF) < 45%) at 12 months follow-up after PCI, as well as 100 control subjects, recruited from the Interventional Cardiology Unit of the IRCCS Policlinico San Donato. The measurements of BACE1, BACE1-AS and βA will be carried out at the Molecular Cardiology Laboratory of the IRCCS Policlinico San Donato. These activities are included among those approved in the RNA_ACS protocol (Ethics Committee of the San Raffaele Hospital - Milan 14/int/2020) "RNA as prognostic biomarkers in patients with acute coronary syndrome"
Group 2:
240 patients with chronic post-ischemic HF and 120 age/sex-matched healthy controls. The recruitment of this group and measurements of BACE1, BACE1-AS and βA will be carried out at the Istituti Clinici Scientifici Maugeri Pavia.
- Conditions
- Heart Failure, Acute Coronary Syndrome
- Being tested
- measurement of RNAs
- Keywords
- long noncoding RNA, heart failure, acute coronary syndrome, biomarkers
- Medical subject headings
- Heart Failure, Acute Coronary Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
measurement of RNAsDiagnostic test
RNAs will be measured in heart tissues and in peripheral blood mononuclear cells
| Study group | Role | What they receive |
|---|---|---|
| Non end-stage heart failure | Measurement of tissutal RNAs in non end-stage heart failure patients undergoing to left ventricle reconstruction Receives: Diagnostic Test: measurement of RNAs | |
| ACS patients | Measurement of circulating RNAs in acute coronary syndrome (ACS) patients treated with percutaneous angioplasty and undergoing to ventricle remodelling Receives: Diagnostic Test: measurement of RNAs | |
| HF patients | Measurement of circulating RNAs in heart failure patients Receives: Diagnostic Test: measurement of RNAs | |
| Controls | Measurement of RNAs in individuals not affected by cardiovascular diseases Receives: Diagnostic Test: measurement of RNAs |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cardiac tissutal RNAs expression
The RNAs cardiac tissutal expression of non- and end-stage heart failure patients compared to controls
Measured: From year 1 to year 3
Peripheral blood RNAs expression in ACS
The RNAs expression in peripheral blood mononuclear cells of acute coronary syndrome patients treated with percutaneous angioplasty and remodelling compared to controls
Measured: From year 1 to year 3
Peripheral blood RNAs expression in heart failure
The RNAs expression in peripheral blood mononuclear cells of heart failure patients compared to controls
Measured: From year 1 to year 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2024
- Study start12 Mar 2021
- Primary completion30 Nov 2024
- Study completion30 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by IRCCS Policlinico S. DonatoThe sponsor's other registered studies.
- 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
- Retrospective
- Enrolment
- 630 participants (actual)
Sponsor and investigators
- Lead sponsor
- IRCCS Policlinico S. Donato
- Sponsor type
- University, hospital or other
- Collaborators
- Istituti Clinici Scientifici Maugeri di Pavia
- Responsible party
- Principal investigator, Fabio Martelli, IRCCS Policlinico S. Donato
- Investigators
- Fabio Martelli, PhD, Principal investigator, IRCCS Policlinico S. Donato
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06213493
- Sponsor's protocol ID
- BACE1AS_HF- RF-2019-12368521
- Acronym
- BACE1AS-HF
- Status last verified
- Apr 2025
- First submitted
- 10 Jan 2024
- Last updated
- 30 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of the BACE1-AS Long Noncoding RNA in Ischemic Heart Failure
- ClinicalTrials.gov ID
- NCT06213493
- Acronym / sponsor ID
- BACE1AS-HF / BACE1AS_HF- RF-2019-12368521
- Conditions
- Heart Failure, Acute Coronary Syndrome
- Keywords
- long noncoding RNA, heart failure, acute coronary syndrome, biomarkers
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 630 participants (actual)
- Lead sponsor
- IRCCS Policlinico S. DonatoUniversity, hospital or other
- Collaborators
- Istituti Clinici Scientifici Maugeri di Pavia
- Study start
- 12 Mar 2021 (actual)
- Primary completion
- 30 Nov 2024 (actual)
- Study completion
- 30 Nov 2024 (actual)
- First posted
- 19 Jan 2024 (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.
The objective of this project is 1) to explore the clinical relevance of BACE1-AS and BACE1 as therapeutic targets and 2) to evaluate their potentiality as biomarkers in ischemic heart failure (HF).
The first aim will be studied by validating in left ventricle biopsies in patients with post-ischemic heart failure the transcriptome and DNA methylation status data obtained in cell lines where the expression of BACE1-AS has been modulated.
The investigation of BACE1-AS and BACE1 as biomarkers will be obtained by using peripheral blood mononuclear cells (PBMCs) from patients with acute coronary syndrome (ACS) treated with percutaneous angioplasty (PCI) procedure and undergoing to left ventricular remodeling. Furthermore, PBMCs from patients with chronic ischemic HF recruited from the Istituti Clinici Scientifici Maugeri Pavia will be also used. From the data obtained from these patients and from non-decompensated subjects, the levels of BACE1-AS and BACE1 in the blood will be measured and correlated with each other and with β-amyloid levels (βA), as well as with clinically relevant parameters.
Detailed description
1.1) Validation of transcriptomic data obtained in vitro: The transcriptome of the AC16 cardiomyocyte cell line in which the expression of BACE1-AS was induced by lentivirus vectors will be analyzed, thus identifying the transcripts specifically modulated by BACE1-AS. The data obtained in vitro will be validated by analyzing the RNAs extracted from 20 HF patients and 20 controls. These RNA samples are already available thanks to the RNA_HF_AS project "Study of the transcriptome in heart failure and aortic stenosis" (San Raffaele Hospital - Milan, Ethics Committee CE 85/int/2016).
1.2) Validation of epigenetic data: The effect of BACE1-AS on the state of DNA methylation will be studied in the AC16 cardiomyocyte cell line. In over-expressing BACE1-AS cells, DNA hypomethylation will be evaluated by MS-HRM and pyrosequencing studies of bisulfite-modified genomic DNA of 69 enhancer sequences identified by us as candidates in preliminary studies. The data thus obtained will be validated in 20 cardiac biopsies from patients with post-ischemic HF and in 20 controls. Left ventricular biopsies will be taken after obtaining informed consent from 20 patients suffering from non-terminal dilated cardiomyopathy (DCM) undergoing left ventricular reconstruction (SVR) surgery at the San Donato Policlinico. A sufficient number of samples with these characteristics have already been obtained from IRCCS Policlinico San Donato as part of the RNA_HF_AS project (San Raffaele Hospital - Milan, Ethics Committee CE 85/int/2016). and not completely used for the study.
1.3) Study of the expression levels of BACE1-AS, BACE1 in PBMC of patients with ischemic cardiomyopathy.
The expression levels of BACE1 and BACE1-AS will be measured in PBMCs from the following groups:
Group 1:
130 ACS patients with left ventricular systolic dysfunction (left ventricular ejection fraction (LVEF) < 45%) at 12 months follow-up after PCI, as well as 100 control subjects, recruited from the Interventional Cardiology Unit of the IRCCS Policlinico San Donato. The measurements of BACE1, BACE1-AS and βA will be carried out at the Molecular Cardiology Laboratory of the IRCCS Policlinico San Donato. These activities are included among those approved in the RNA_ACS protocol (Ethics Committee of the San Raffaele Hospital - Milan 14/int/2020) "RNA as prognostic biomarkers in patients with acute coronary syndrome"
Group 2:
240 patients with chronic post-ischemic HF and 120 age/sex-matched healthy controls. The recruitment of this group and measurements of BACE1, BACE1-AS and βA will be carried out at the Istituti Clinici Scientifici Maugeri Pavia.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Non end-stage heart failure | – | Diagnostic Test: measurement of RNAsMeasurement of tissutal RNAs in non end-stage heart failure patients undergoing to left ventricle reconstruction |
| ACS patients | – | Diagnostic Test: measurement of RNAsMeasurement of circulating RNAs in acute coronary syndrome (ACS) patients treated with percutaneous angioplasty and undergoing to ventricle remodelling |
| HF patients | – | Diagnostic Test: measurement of RNAsMeasurement of circulating RNAs in heart failure patients |
| Controls | – | Diagnostic Test: measurement of RNAsMeasurement of RNAs in individuals not affected by cardiovascular diseases |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- 1. Left ventricular biopsies from patients with post-ischemic HF. Left ventricular tissue fragments from patients with post-ischemic HF undergoing to left ventricular reconstruction (SVR) will be used 2. Patients with acute coronary syndrome and left ventricular dysfunction 12 months after percutaneous angioplasty Control group will be represented by patients suffering from unstable angina. 3. Patients with chronic post-ischemic HF (recruitment at the Istituti Clinici Scientifici Maugeri Pavia ICS) All patients admitted with a diagnosis of chronic heart failure or an ischemic or "acute" basis due to exacerbation.
Key inclusion criteria (12 listed)
- All patients admitted to Rehabilitation Cardiology at the Cardiology Department of ICS Maugeri with a diagnosis of chronic heart failure on an ischemic or "acute" basis due to exacerbation of chronic heart failure due to previous ischemia and whose therapies have been optimized at the moment of enlistment.
- NYHA Class II-III at the time of enlistment;
- Age over 18 years;
- Informed consent signed at the time of enrollment in the study.
Key exclusion criteria (33 listed)
- Patients with ACS and left ventricular dysfunction 12 months after percutaneous angioplasty
- heparin aspirin, clopidogrel, ticlopidine, sirolimus, everolimus.
- Patients with chronic post-ischemic HF ( recruitment at the Istituti Clinici Scientifici Maugeri Pavia)
- Denial of informed consent;
- End-stage renal disease;
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 |
|---|---|---|
| measurement of RNAsRNAs will be measured in heart tissues and in peripheral blood mononuclear cells | Diagnostic test | ACS patients, Controls, HF patients, Non end-stage heart failure |
Primary outcome
Cardiac tissutal RNAs expression
Time frame: From year 1 to year 3
The RNAs cardiac tissutal expression of non- and end-stage heart failure patients compared to controls
Peripheral blood RNAs expression in ACS
Time frame: From year 1 to year 3
The RNAs expression in peripheral blood mononuclear cells of acute coronary syndrome patients treated with percutaneous angioplasty and remodelling compared to controls
Peripheral blood RNAs expression in heart failure
Time frame: From year 1 to year 3
The RNAs expression in peripheral blood mononuclear cells of heart failure patients compared to 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 30 Apr 2025.
- 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.
Fabio Martelli, PhD principal investigator
IRCCS Policlinico S. Donato
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 and Acute Coronary Syndrome, run by IRCCS Policlinico S. Donato 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 12 inclusion and 33 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 30 Apr 2025. 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?
Cardiac tissutal RNAs expression (time frame: From year 1 to year 3). 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?
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 30 Apr 2025.