Extremes of Coronary Artery Disease and Normality:CAD Extremes

NCT05775445 | Recruiting

• 1 other identifier: 2022/2366
• Study Type: observational
• Target: 1,500
• Locations: 1 country
• Sites: 1

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).

Conditions

Coronary Artery Disease

Outcome Measures

Primary Outcomes (2)

• Using sequencing analysis to develop treatment to protect against Coronary artery disease

  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

  5 years

• Develop treatment for Coronary artery disease

  To aid in the development of novel preventive and treatment strategies for coronary artery disease

  5 years

Study Arms (4)

Group 1 (significant CAD, low risk factors)

1. Evidence of significant CAD a. Coronary angiogram or CT coronary angiogram with documented stenosis \>=50% in left main or \>=70% in major epicardial vessel or major branches (LAD, LCX, RCA) AND all of the following 2. Age \</= 45 for males and \</= 50 for females 3. Absence of diabetes mellitus 4. Absence of tobacco use 5. No prior CVA or PAD

Procedure: Blood draw

Group 2 (minor CAD, high risk factors)

1. No evidence of significant CAD a. Coronary angiogram or CT coronary angiogram with \<50% stenosis in major blood vessel/branch 2. No prior history of clinical CAD, PAD or CVA with one of the 3. Age \>65 with 1. Diabetes mellitus \>5years; or 2. End Stage Renal Failure (ESRF), regardless of duration or 3. Framingham risk score \> 10% 4. Diabetes \>10 years 5. End Stage Renal Failure (ESRF) \> 5 years 6. Age \>80

Procedure: Blood draw

Group 3 (signifcant CAD, high risk factors)

1\. Evidence of significant CAD with one of the following: 1. age\>65 2. Diabetes mellitus 3. End Stage Renal Failure (ESRF) 4. Framingham risk score \>10%

Procedure: Blood draw

Group 4 Control group

1\. No evidence of significant CAD and all of the following: 1. Age \<55 for males, \<65 for females 2. Absence of diabetes mellitus 3. Absence of CKD 4. Absence of tobacco use

Procedure: Blood draw

Interventions

Blood draw PROCEDURE

2 6ml blood tubes will be collected from patient

Group 1 (significant CAD, low risk factors); Group 2 (minor CAD, high risk factors); Group 3 (signifcant CAD, high risk factors); Group 4 Control group

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Coronary Artery Disease patients with high risk factors/ low risk factors No Coronary Artery disease but with high risk factors

You may qualify if:

• Group 1:
• Evidence of significant CAD a. Coronary angiogram or CT coronary angiogram with documented stenosis \>=50% in left main or \>=70% in major epicardial vessel or major branches (LAD, LCX, RCA)
• AND all of the following
• Age \</= 45 for males and \</= 50 for females
• Absence of diabetes mellitus
• Absence of tobacco use
• No prior CVA or PAD
• Group 2
• Evidence of significant CAD
• Coronary angiogram or CT coronary angiogram with documented stenosis \>=50% in left main or \>=70% in major epicardial vessel or major branches (LAD, LCX, RCA)
• AND all of the following
• Age \</= 45 for males and \</= 50 for females
• Absence of diabetes mellitus
• Absence of tobacco use
• No prior CVA or PAD

You may not qualify if:

• Prior history of cancer (excludes pre-cancerous lesions)
• Expected life expectancy less than 1 year
• Known autoimmune disease
• Psychiatric illness
• Chronic lung disease requiring long term medications or oxygen
• Chronic infective disease, including tuberculosis, hepatitis B and C; and HIV
• Inability to comply with study protocol
• Any other acute or chronic medical or physical condition deemed by the investigator to affect study outcomes

Sponsors & Collaborators

• National Heart Centre Singapore: lead
• Duke-NUS Graduate Medical School: collaborator

Study Sites (1)

National Heart Centre Singapore

Singapore, 169609, Singapore

RECRUITING

Related Publications (4)

• Paulin N, Viola JR, Maas SL, de Jong R, Fernandes-Alnemri T, Weber C, Drechsler M, Doring Y, Soehnlein O. Double-Strand DNA Sensing Aim2 Inflammasome Regulates Atherosclerotic Plaque Vulnerability. Circulation. 2018 Jul 17;138(3):321-323. doi: 10.1161/CIRCULATIONAHA.117.033098. No abstract available.

  PMID: 30012706 BACKGROUND

• Widmaier EP, Gornstein ER, Hennessey JL, Bloss JM, Greenberg JA, Kunz TH. High plasma cholesterol, but low triglycerides and plaque-free arteries, in Mexican free-tailed bats. Am J Physiol. 1996 Nov;271(5 Pt 2):R1101-6. doi: 10.1152/ajpregu.1996.271.5.R1101.

  PMID: 8945941 BACKGROUND

• Alwan A, Maclean DR, Riley LM, d'Espaignet ET, Mathers CD, Stevens GA, Bettcher D. Monitoring and surveillance of chronic non-communicable diseases: progress and capacity in high-burden countries. Lancet. 2010 Nov 27;376(9755):1861-8. doi: 10.1016/S0140-6736(10)61853-3. Epub 2010 Nov 10.

  PMID: 21074258 BACKGROUND

• Duewell P, Kono H, Rayner KJ, Sirois CM, Vladimer G, Bauernfeind FG, Abela GS, Franchi L, Nunez G, Schnurr M, Espevik T, Lien E, Fitzgerald KA, Rock KL, Moore KJ, Wright SD, Hornung V, Latz E. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature. 2010 Apr 29;464(7293):1357-61. doi: 10.1038/nature08938.

  PMID: 20428172 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

2 tubes of EDTA will be collected per subject

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Khyung Keong Yeo

  National Heart Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aishah Toh

CONTACT

67042282; aishah.toh@nhcs.com.sg

Pei Yi Ho

CONTACT

67042234; ho.pei.yi@nhcs.com.sg

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2023
• First Posted: March 20, 2023
• Study Start: May 30, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: February 21, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)