Ignite Creation Date:
2024-10-26 @ 3:40 PM
Last Modification Date:
2024-10-26 @ 3:40 PM
Study NCT ID:
NCT06601153
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-09-15
Brief Title:
Health Improvements by Understanding the Determinants of Residual Risk in Coronary Artery Disease and New Targets for Prevention and Treatment
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Health Improvements by Understanding Residual Risk in CAd and NEw Targets for Preventiontreatment - HURRICANE
Status:
RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
HURRICANE
Brief Summary:
Current medical treatments in patients with stable coronary artery disease CAD mainly target established risk factors and are able to reduce morbidity and mortality but still leave a substantial residual risk of coronary artery disease progression and events The main hypothesis of this study is that metabolic derangement including pre-diabetes elevated levels of triglycerides low levels and functionality of high-density lipoprotein cholesterol often associated with a chronic inflammatory state is a currently unrecognized and undertreated conditon which could be the most relevant determinant of residual risk
The goal of HURRICANE observational study is to discover specific individual geneticmolecular profiles subtending emerging cardiometabolic and vascular risk patterns and associating with a more severe and progressive coronary artery disease We will thus develop and preliminary validate new predictive models for the recognition of high-risk patients and explore possible new targets for individualized preventive treatment
The severity extent and progression of coronary plaques will be assessed by qualitative and quantitative analysis of cardiac computed tomography CCT performed in retrospective and prospective cohorts of patients with stable coronary disease
The goal of HURRICANE observational study is to discover specific individual geneticmolecular profiles subtending emerging cardiometabolic and vascular risk patterns and associating with a more severe and progressive coronary artery disease We will thus develop and preliminary validate new predictive models for the recognition of high-risk patients and explore possible new targets for individualized preventive treatment
The severity extent and progression of coronary plaques will be assessed by qualitative and quantitative analysis of cardiac computed tomography CCT performed in retrospective and prospective cohorts of patients with stable coronary disease
Detailed Description:
HURRICANE is an observational clinical study performed in retrospective and prospective cohorts of patients with stable CAD to assess the role of emerging cardiometabolic and vascular risk determinants to predict severe and progressive coronary atherosclerosis documented by advanced CCT imaging
The population of the retrospective study consists of two parallel independent groups of patients enrolled in previous clinical trials focused on blood and CCT biomarkers of CAD All participants are assessed for eligibility to the current study which includes in particular availability of blood samples in bio-bank and of interpretable CCT exams For each cohort and for the whole retrospective population 561 patients clinical variables demographic data cardiovascular risk factors history of previous CAD symptoms and medications and conventional circulating biomarkers lipid and glucose metabolism systemic inflammation liver and kidney function are recorded The coronary imaging variables which will provide the disease presence and severity end-points will be derived from qualitative and semiquantitative analyses of CCT exams according to CAD-RADS 20 classification system
The population of the prospective longitudinal study will include 400 patients referred at IRCCS SYNLAB SDN in Naples and FTGM in Pisa over a 12 months period to a clinically indicated CCT for suspected CAD signing a written informed consent and fulfilling Inclusion and exclusion criteria At baseline patients will be characterized as in the retrospective study same clinical variables conventional circulating biomarkers and CCT imaging variables and blood samples will be collected and stored in the dedicated Bio-Bank for advanced geneticmolecular analyses They will be submitted to monitoring visits and a last follow-up visit at 12 months when compliance to medical treatment and events will be registered A second blood sample will be collected and stored in dedicated Bio-Bank for advanced molecular analyses A second CCT scan will be performed at 12 months with the same scanner at the same institution by the use of a state-of-the art CCT technology with high spatial and temporal resolution to provide quantitative measurements of coronary plaque volumes and coronary plaque composition which will be used to define the disease progression end-points
Qualitative and semiquantitative analyses of CCT exams will be performed by radiologists according to CAD-RADS 20 classification systemin both the retrospective and prospective populations In the prospective population CCT images at enrollment and follow-up will also be quantitatively analyzed to define evolving CAD phenotypes Quantitative analysis will be performed on visually identified plaques using a dedicated software package QAngio CT Research Edition version 3120 Medis Medical Imaging Systems Leiden the Netherlands to generate detailed output on the lumen and plaque statistics including the degree of stenosis lesion length vessel volume plaque burden plaque volume and plaque components according to the virtual histology classification dense calcium necrotic core fibrous-fatty fibrous and media Additional CT-derived parameters will also be assessed in particular epicardial and perivascular adipose tissue to be tested in the predictive models of CAD evolution and to be entered in a Machine Learning data analysis as potential variables of the pathophysiologic CAD network
Circulating biomarkers will be evaluated by standard methodologies of clinical chemistry laboratories at the two participant clinical centers and specific circulating biomarkers will be analyzed at the IFC-CNR Core-Lab in both the retrospective and the prospective populations In particular additional markers of lipid metabolism and adipose tissue function endothelial function and atherosclerotic burden will be evaluated by dedicated immunoassays while markers of myocardial damagefunction will be evaluated by automatized immunoassays The inflammatory profile will be assessed by multiplex cytokine screensOmics analyses in both populations will include lipidomic with the assessment of circulating lipid species using mass spectrometry and genetic profiling by GWAS Genome-Wide Association Study performed by an external provider Genomix4Life using new generation microarray technology to genotype single-nucleotide variants SNVs In representative extreme groups of patients from the prospective population a specific panel of 88 candidate genes involved in lipidglucose homeostasis endothelialvascular function and systemic inflammation together with other relevant genes emerging from the GWAS analysis will be sequenced for known and unknown variants at FTGM by NGS Next Generation Sequencing approach The library preparation for NGS will be performed using the Illumina DNA Prep with Enrichment Kit Base-Space Variant Interpreter software will be used to annotate filter and interpret the variants The degree of pathogenicity will be also assessed on VarSome httpsvarsomecom and GWAS Catalog httpswwwebiacukgwas search engines and impact analysis tools for human genetic variation The variants identified as pathogenetically relevant in the subjects with extreme phenotypes will then be assessed in the rest of the population Moreover miRNAs putatively associated with relevant gene variants and screened by in silico bioinformatic analysis will be assessed by qPCR
The population of the retrospective study consists of two parallel independent groups of patients enrolled in previous clinical trials focused on blood and CCT biomarkers of CAD All participants are assessed for eligibility to the current study which includes in particular availability of blood samples in bio-bank and of interpretable CCT exams For each cohort and for the whole retrospective population 561 patients clinical variables demographic data cardiovascular risk factors history of previous CAD symptoms and medications and conventional circulating biomarkers lipid and glucose metabolism systemic inflammation liver and kidney function are recorded The coronary imaging variables which will provide the disease presence and severity end-points will be derived from qualitative and semiquantitative analyses of CCT exams according to CAD-RADS 20 classification system
The population of the prospective longitudinal study will include 400 patients referred at IRCCS SYNLAB SDN in Naples and FTGM in Pisa over a 12 months period to a clinically indicated CCT for suspected CAD signing a written informed consent and fulfilling Inclusion and exclusion criteria At baseline patients will be characterized as in the retrospective study same clinical variables conventional circulating biomarkers and CCT imaging variables and blood samples will be collected and stored in the dedicated Bio-Bank for advanced geneticmolecular analyses They will be submitted to monitoring visits and a last follow-up visit at 12 months when compliance to medical treatment and events will be registered A second blood sample will be collected and stored in dedicated Bio-Bank for advanced molecular analyses A second CCT scan will be performed at 12 months with the same scanner at the same institution by the use of a state-of-the art CCT technology with high spatial and temporal resolution to provide quantitative measurements of coronary plaque volumes and coronary plaque composition which will be used to define the disease progression end-points
Qualitative and semiquantitative analyses of CCT exams will be performed by radiologists according to CAD-RADS 20 classification systemin both the retrospective and prospective populations In the prospective population CCT images at enrollment and follow-up will also be quantitatively analyzed to define evolving CAD phenotypes Quantitative analysis will be performed on visually identified plaques using a dedicated software package QAngio CT Research Edition version 3120 Medis Medical Imaging Systems Leiden the Netherlands to generate detailed output on the lumen and plaque statistics including the degree of stenosis lesion length vessel volume plaque burden plaque volume and plaque components according to the virtual histology classification dense calcium necrotic core fibrous-fatty fibrous and media Additional CT-derived parameters will also be assessed in particular epicardial and perivascular adipose tissue to be tested in the predictive models of CAD evolution and to be entered in a Machine Learning data analysis as potential variables of the pathophysiologic CAD network
Circulating biomarkers will be evaluated by standard methodologies of clinical chemistry laboratories at the two participant clinical centers and specific circulating biomarkers will be analyzed at the IFC-CNR Core-Lab in both the retrospective and the prospective populations In particular additional markers of lipid metabolism and adipose tissue function endothelial function and atherosclerotic burden will be evaluated by dedicated immunoassays while markers of myocardial damagefunction will be evaluated by automatized immunoassays The inflammatory profile will be assessed by multiplex cytokine screensOmics analyses in both populations will include lipidomic with the assessment of circulating lipid species using mass spectrometry and genetic profiling by GWAS Genome-Wide Association Study performed by an external provider Genomix4Life using new generation microarray technology to genotype single-nucleotide variants SNVs In representative extreme groups of patients from the prospective population a specific panel of 88 candidate genes involved in lipidglucose homeostasis endothelialvascular function and systemic inflammation together with other relevant genes emerging from the GWAS analysis will be sequenced for known and unknown variants at FTGM by NGS Next Generation Sequencing approach The library preparation for NGS will be performed using the Illumina DNA Prep with Enrichment Kit Base-Space Variant Interpreter software will be used to annotate filter and interpret the variants The degree of pathogenicity will be also assessed on VarSome httpsvarsomecom and GWAS Catalog httpswwwebiacukgwas search engines and impact analysis tools for human genetic variation The variants identified as pathogenetically relevant in the subjects with extreme phenotypes will then be assessed in the rest of the population Moreover miRNAs putatively associated with relevant gene variants and screened by in silico bioinformatic analysis will be assessed by qPCR
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None