The purpose of the GLOBAL study is to perform whole-genome genotyping, next-generation deep resequencing, gene expression profiling, metabolomics, lipidomics and proteomics of atherosclerosis in patients phenotyped using advanced CT-based imaging…
ID
Source
Brief title
Condition
- Coronary artery disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of this study is to understand novel genomic associations
of CAD by using advanced cardiovascular imaging for CAD phenotyping and
next-generation whole genome genotyping and sequencing.
Secondary outcome
A secondary objective of this study is to understand novel gene expression,
metabolomic, lipidomic and proteomic associations of CAD by using advanced
cardiovascular imaging and state-of-the-art biomarker approaches.
Background summary
Atherosclerosis is responsible for coronary artery disease (CAD) and
cerebrovascular disease, the first and third leading causes of morbidity and
mortality in both the United States and worldwide, as well as for peripheral
arterial disease, which is the leading medical cause of limb loss.
Atherosclerosis, as any other disease, is the result of very complex
interactions between genetic susceptibility and the environment. Genetic
information is encoded in the deoxyribonucleic acid (DNA) is fully inherited
and changes minimally during one*s lifetime. While over 99.9% of the genetic
code (DNA) is identical in all human beings, differences in the remaining 0.1%
are responsible for individual traits as well as for disease activities; 80% of
such these differences are so-called *single nucleotide polymorphisms*, or
*SNP*s*. To date, approximately 4 million SNP*s have been identified. These
genetic susceptibilities interact with environmental factors and result in the
expression of genes in the blood and tissues in the form of ribonucleic acid
(RNA). Gene expression (RNA) manifests itself as actual traits, or
*phenotypes* (intermediate phenotypes), such as lipid and lipoprotein levels,
inflammatory milieu, blood pressure, glycemic environment, etc., and these
traits act in concert in the development of diseases (ultimate phenotype), such
as atherosclerosis, culminating in sudden cardiac death, heart attack, stroke
and critical limb disease.
Study objective
The purpose of the GLOBAL study is to perform whole-genome genotyping,
next-generation deep resequencing, gene expression profiling, metabolomics,
lipidomics and proteomics of atherosclerosis in patients phenotyped using
advanced CT-based imaging modalities of atherosclerosis. If successful,
results of this study may help in developing diagnostic tests that will assist
physicians in identifying individuals at greatest risk for significant CAD.
Study design
The GLOBAL study is an international multi-center, prospective study designed
to enroll up to 10,000 consecutive eligible subjects who are clinically
referred for coronary CT angiography for assessment of suspected coronary
artery disease (CAD). Subjects will be enrolled at up to 50 clinical
institutions globally.
Study burden and risks
The risks associated with the Study (for the blood draw) are related to blood
draw risks as follows: The safety of phlebotomy has been well established.
When blood is drawn from a vein, there may be temporary discomfort and a
minimal risk for local bruising, infection, or blockage of the vein. Fainting
occurs rarely. All phlebotomy in this study will be performed in accordance
with standard hospital policy and suitable precautions will be taken to
minimize all risks. There is a rare risk that the contents of the PAXgene tube
(RNA stabilizing agent) could reflux into the vein. The GLOBAL Study Laboratory
Manual contains instructions regarding drawing the PAXgene tubes after blood
flow has been established with the other blood tubes and maintaining the
PAXgene tube below the stick level and at an appropriate angle, for minimizing
these risks.
There are no anticipated benefits in immediate care to subjects participating
in this Study and no clinical management decisions are being made with
information from the study. If successful, results of this study may benefit
future patients through development of diagnostic tests that will assist
physicians in identifying individuals at greatest risk for significant CAD.
N. 5th Street, Suite 103 737
Virginia 23219
US
N. 5th Street, Suite 103 737
Virginia 23219
US
Listed location countries
Age
Inclusion criteria
1. Ages 18-90
2. White and of Non-Hispanic or Non-Latino origin
3. Referral for coronary CT angiography to evaluate for presence of CAD
4. The patient has signed the appropriate Institutional Review Board approved Informed Consent
Form
Exclusion criteria
General Exclusion Criteria
1. Immunosuppressive or immunomodulatory therapy including any dose of systemic corticosteroids
in the preceding 30 days (except if steroids are administered as pre-medication prior to contrast
administration for CT scan within 24 hours)
2. Chemotherapy in the preceding year
3. Major surgery in the preceding 2 months
4. Blood or blood product transfusion in the preceding 2 months
5. Subjects for whom coronary CT angiography is contraindicated per institutional standard of care
6. Subjects with previous coronary arterial revascularization (PCI or CABG)
7. Subjects with atrial fibrillation/flutter or frequent irregular or rapid heart rhythms, which occurred
within the past 3 months
8. Subjects with a pacemaker or implantable cardioverter-defibrillator implant
9. Active congestive heart failure or the presence of known non-ischemic cardiomyopathy
10. Known genetic disorders of atherosclerosis, lipid or lipoprotein metabolism
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT01738828 |
| CCMO | NL44384.091.13 |