Ignite Creation Date:
2024-05-06 @ 7:59 PM
Last Modification Date:
2024-10-26 @ 3:18 PM
Study NCT ID:
NCT06213493
Status:
RECRUITING
Last Update Posted:
2024-01-19
First Post:
2024-01-10
Brief Title:
Bace1as Role in Heart Failure BACE1AS-HF
Sponsor:
IRCCS Policlinico S Donato
Organization:
IRCCS Policlinico S Donato
Study Overview
Official Title:
Role of the BACE1-AS Long Noncoding RNA in Ischemic Heart Failure
Status:
RECRUITING
Status Verified Date:
2024-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
BACE1AS-HF
Brief 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
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 we will evaluate whether the levels of BACE1-AS and BACE1 in the blood are correlated with each other and with β-amyloid levels βA as well as with clinically relevant parameters
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 we will evaluate whether the levels of BACE1-AS and BACE1 in the blood are correlated with each other and with β-amyloid levels βA as well as with clinically relevant parameters
Detailed Description:
11 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 number of the register of opinions of the Ethics Committee of the San Raffaele Hospital - Milan CE 85int2016
12 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 number of the register of opinions of the Ethics Committee of the San Raffaele Hospital - Milan CE 85int2016 and not completely used for the study
13 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 14int2020 RNA as prognostic biomarkers in patients with acute coronary syndrome
Group 2
240 patients with chronic post-ischemic HF and 120 agesex-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
12 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 number of the register of opinions of the Ethics Committee of the San Raffaele Hospital - Milan CE 85int2016 and not completely used for the study
13 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 14int2020 RNA as prognostic biomarkers in patients with acute coronary syndrome
Group 2
240 patients with chronic post-ischemic HF and 120 agesex-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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None