Ignite Creation Date:
2024-05-06 @ 6:45 PM
Last Modification Date:
2024-10-26 @ 2:54 PM
Study NCT ID:
NCT05775445
Status:
RECRUITING
Last Update Posted:
2024-02-21
First Post:
2023-02-10
Brief Title:
Extremes of Coronary Artery Disease and NormalityCAD Extremes
Sponsor:
National Heart Centre Singapore
Organization:
National Heart Centre Singapore
Study Overview
Official Title:
Extremes of Coronary Artery Disease and Normality Understanding Novel Causative and Protective Factors in the Development of Coronary Artery Disease CAD Extremes
Status:
RECRUITING
Status Verified Date:
2024-02
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:
None
Brief Summary:
In the field of cardiovascular medicine there are two differing groups of patients that remain puzzling to clinicians patients who are not expected to have coronary artery disease CAD yet are diagnosed with significant CAD and those who are have multiple risk factors for CAD but do not have CAD Bats exhibit unique phenotypes including long lifespans and likely reduced atherosclerosis Prior work has identified multiple molecular mechanisms of suppressing the activation of inflammasomes causally linked to atherosclerosis The investigators hypothesize there are different molecular markers that confer protection or increased risk for CAD some of which may be similar to bats Thus the aim of this study is to identify molecular markers that contribute to or are protective against acute coronary syndrome ACS through analyzing the genetics peripheral blood and atherosclerotic samples from both extreme patient groups using single-cell RNA sequencing and multi-omics approach In addition novel anti-atherosclerotic mechanisms and factors from bat studies will be assessed in the human samples Identification of novel targets that prevent or cause CAD has the potential to aid in the early identification of high-risk patients and development of new therapeutics to combat this growing epidemic To conduct this study patients who have undergone a coronary angiogram or a CT coronary angiogram that fall into the both extremes will be recruited and blood samples will be taken for the above analysis These will be compared to a group of controls low risk without disease and high risk with disease
Detailed Description:
Cardiovascular disease CVD imposes much mortality and morbidity worldwide Large population-based studies in Western cohorts eg Framingham Heart Study have formed the foundations of knowledge on the traditional risk factors of cardiovascular disease Despite this large gaps in the knowledge of CVD still exist The clinical conundrum of the extremes of spectrums of CVD continues to baffle clinicians and researchers alike These include patients without any major cardiovascular risk factors developing acute coronary syndromes ACS at a young age At the other end of the spectrum there are not uncommonly patients with full-house cardiovascular risk factors with minor or no coronary artery disease
Similar to the phenotype observed in patients with risk factors with little coronary artery disease the animal bats exhibit unique phenotypes including long lifespans and likely reduced atherosclerosis A study has shown that the animal bats are able to have plaque-free arteries despite being on a high-fat diet with high plasma cholesterol which are associated to the development of atherosclerosis The pathogenesis of atherosclerosis has been linked to inflammasome activation an intracellular multi-protein complexes that engage in innate immune defenses An inflammasome typically consists of a sensor that detects pathogens or danger signals an adaptor and an effector that initiates pro-inflammatory responses Aberrations in inflammasomes have been causally linked to numerous diseases including viral infections autoimmune metabolic and neurodegenerative diseases However no effective treatment options have been established thus far Importantly multiple molecular mechanisms of suppressing the activation of inflammasomes causally linked to atherosclerosis have already been identified in bats These include dampened sensors and complementary regulation of the effector and downstream cytokine which could be protective factors of atherosclerosis These make bats excellent model for anti-atherosclerosis research
Recent advancements in technology have led to exciting developments in our understanding of the development and prevention of CVD The use of big data and deep learning advancements in genomics metabolomics proteomics have the possibility of transforming this field Recent modern prospective population-based studies eg The MURDOCK study aim to reclassify cardiovascular risk using integrated clinical and molecular biosignatures However these studies are based primarily in Western populations Ethnic differences in CVD exist and currently in Asia there is a dearth of such advanced data The aim of this study is thus to identify molecular and inflammasome markers that contribute or are protective against ACS using single-cell sequencing and multi-omics approach and on top of that using animal models of bats and mice as comparison to humans Genomic metabolomics proteomics and scRNA-seq may seek to help answer some of this questions and better improve understanding of the development of CVD potentially developing novel preventive and management strategies
The specific aims of the project are as follows
To use advanced genomic metabolomics proteomic and single-cell RNA sequencing scRNA-seq analysis to understand novel factors influencing the development of coronary artery disease as well as protection against coronary artery disease
To assess and validate the novel anti-atherosclerotic mechanisms and factors from bat studies in the human samples
To aid in the development of novel preventive and treatment strategies for coronary artery disease
Study population
The primary focus will be on two patient groups Group 1 patients will be recruited to study the novel factors influencing the development of coronary artery disease This will include patients with known significant coronary artery disease but without any significant major cardiovascular risk factors
Group 2 patients will be recruited to study the novel factors protective against the development of CAD This will include patients at high risk of developing CAD but no significant CAD
a group of controls will be recruited Group 3 and Group 4 for comparison high risk with CAD and low risk with no CAD Participants from Group 4 may be obtained from existing registriescohorts
Patients will be recruited from two sources
1 Prospective recruitment from the coronary catheterization lab CT lab ward or clinic
2 Retrospective review of angiograms from the coronary catheterization lab and CT coronary angiogram
Informed consent will be obtained If the patient is agreeable to take part clinical data will be obtained from his medical records The patient will also be required to fill up a questionnaire on the patients demographics lifestyle and medical history etc Blood will be obtained from the patients for genetic proteomic and metabolic screening
Other data will be collected if available as part of routine care
1 Demographic and clinical characteristics data
2 Quality-of-life
3 Basic blood investigations Basic blood investigations include FBC renal panel HbA1c fasting glucose LFT fasting lipids hs-CRP ESR ANA anti-dsDNA RF anticardiolipin antibodies homocysteine protein C protein S thyroid function tests etc
4 Investigations ECG CT Echo MRI holter nuclear imaging etc
5 Biobanking and WGS
6 Metabolomic panel
Clinical Follow-up data
1 Mortality data
2 StrokeMIheart failureRevascularization data
3 Coronary angiograms and other investigations as part of clinical follow up
2 Readmissions 3 Quality of life 4 Costs 5 Other clinical outcomes
These will be obtained from medical records or local hospital or national databases
Similar to the phenotype observed in patients with risk factors with little coronary artery disease the animal bats exhibit unique phenotypes including long lifespans and likely reduced atherosclerosis A study has shown that the animal bats are able to have plaque-free arteries despite being on a high-fat diet with high plasma cholesterol which are associated to the development of atherosclerosis The pathogenesis of atherosclerosis has been linked to inflammasome activation an intracellular multi-protein complexes that engage in innate immune defenses An inflammasome typically consists of a sensor that detects pathogens or danger signals an adaptor and an effector that initiates pro-inflammatory responses Aberrations in inflammasomes have been causally linked to numerous diseases including viral infections autoimmune metabolic and neurodegenerative diseases However no effective treatment options have been established thus far Importantly multiple molecular mechanisms of suppressing the activation of inflammasomes causally linked to atherosclerosis have already been identified in bats These include dampened sensors and complementary regulation of the effector and downstream cytokine which could be protective factors of atherosclerosis These make bats excellent model for anti-atherosclerosis research
Recent advancements in technology have led to exciting developments in our understanding of the development and prevention of CVD The use of big data and deep learning advancements in genomics metabolomics proteomics have the possibility of transforming this field Recent modern prospective population-based studies eg The MURDOCK study aim to reclassify cardiovascular risk using integrated clinical and molecular biosignatures However these studies are based primarily in Western populations Ethnic differences in CVD exist and currently in Asia there is a dearth of such advanced data The aim of this study is thus to identify molecular and inflammasome markers that contribute or are protective against ACS using single-cell sequencing and multi-omics approach and on top of that using animal models of bats and mice as comparison to humans Genomic metabolomics proteomics and scRNA-seq may seek to help answer some of this questions and better improve understanding of the development of CVD potentially developing novel preventive and management strategies
The specific aims of the project are as follows
To use advanced genomic metabolomics proteomic and single-cell RNA sequencing scRNA-seq analysis to understand novel factors influencing the development of coronary artery disease as well as protection against coronary artery disease
To assess and validate the novel anti-atherosclerotic mechanisms and factors from bat studies in the human samples
To aid in the development of novel preventive and treatment strategies for coronary artery disease
Study population
The primary focus will be on two patient groups Group 1 patients will be recruited to study the novel factors influencing the development of coronary artery disease This will include patients with known significant coronary artery disease but without any significant major cardiovascular risk factors
Group 2 patients will be recruited to study the novel factors protective against the development of CAD This will include patients at high risk of developing CAD but no significant CAD
a group of controls will be recruited Group 3 and Group 4 for comparison high risk with CAD and low risk with no CAD Participants from Group 4 may be obtained from existing registriescohorts
Patients will be recruited from two sources
1 Prospective recruitment from the coronary catheterization lab CT lab ward or clinic
2 Retrospective review of angiograms from the coronary catheterization lab and CT coronary angiogram
Informed consent will be obtained If the patient is agreeable to take part clinical data will be obtained from his medical records The patient will also be required to fill up a questionnaire on the patients demographics lifestyle and medical history etc Blood will be obtained from the patients for genetic proteomic and metabolic screening
Other data will be collected if available as part of routine care
1 Demographic and clinical characteristics data
2 Quality-of-life
3 Basic blood investigations Basic blood investigations include FBC renal panel HbA1c fasting glucose LFT fasting lipids hs-CRP ESR ANA anti-dsDNA RF anticardiolipin antibodies homocysteine protein C protein S thyroid function tests etc
4 Investigations ECG CT Echo MRI holter nuclear imaging etc
5 Biobanking and WGS
6 Metabolomic panel
Clinical Follow-up data
1 Mortality data
2 StrokeMIheart failureRevascularization data
3 Coronary angiograms and other investigations as part of clinical follow up
2 Readmissions 3 Quality of life 4 Costs 5 Other clinical outcomes
These will be obtained from medical records or local hospital or national databases
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