Personal Genomics for Preventive Cardiology
Primary Purpose
Coronary Artery Disease
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
genetic risk score for coronary risk factors
Sponsored by
About this trial
This is an interventional prevention trial for Coronary Artery Disease focused on measuring genetic, atherosclerosis, myocardial infarction, risk, preventive cardiology
Eligibility Criteria
Inclusion Criteria:
- Adults age > 18
- Patient seeking cardiovascular risk evaluation
- At intermediate (6-20%) or high risk (> 20%) over 10 years of CAD as defined by Framingham 10 year risk score AND/OR at > 20% risk of CAD over 30 years using the Framingham 30 year risk calculator
- The genetic risk factors have been evaluated predominantly in white/European subjects. However, there is considerable overlap in the genetic architecture of South Asians and Hispanic/Latino populations. Therefore, we will limit our initial studies to these three race/ethnicity groups.
Exclusion Criteria:
- History of myocardial infarction, angina, stroke, peripheral arterial disease, PCI, or CABG
- Already on lipid lowering therapy
- Anticipated survival <1 year (e.g. metastatic cancer)
- Serious conditions that would limit ability to adhere to recommendations (inability to take statins, exercise)
- Already had genetic testing
- Concurrent enrollment in another clinical trial
- Pregnant or breastfeeding
Sites / Locations
- Stanford Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Other
No Intervention
Arm Label
standard of care plus genetic information
usual standard of care without genetic information
Arm Description
Outcomes
Primary Outcome Measures
change in LDL cholesterol
Secondary Outcome Measures
change in weight
change in exercise
medication compliance
non-HDL cholesterol
blood pressure
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01406808
Brief Title
Personal Genomics for Preventive Cardiology
Official Title
A Pilot Randomized Trial of Personal Genomics for Preventive Cardiology
Study Type
Interventional
2. Study Status
Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
August 2011 (undefined)
Primary Completion Date
October 2016 (Actual)
Study Completion Date
August 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to see if providing information to a person on their inherited (genetic) risk of cardiovascular disease (CVD) helps to motivate that person to change their diet, lifestyle or medication regimen to alter their risk.
Detailed Description
Genome wide association studies (GWAS) have identified over 1000 disease associated SNPs, including many related to cardiovascular disease (CVD). Associations have been found for most traditional risk factors including lipids, blood pressure /hypertension, weight/body mass index, smoking behavior, and diabetes. Importantly, GWAS have also identified susceptibility variants for coronary heart disease/ myocardial infarction (CHD/MI), many of which are independent of traditional risk factors and thus cannot currently be assessed by surrogate measures. The first, and so far the strongest, of these signals was found in the 9p21.3 locus and are associated with a 20-40% increase in the relative risk of coronary heart disease among Caucasian and East Asian populations. Like most of the associations identified to date, the function of the non-coding 9p21.3 chromosomal region remains unclear. These markers predict disease and can modesty improve reclassification indices. For instance, in a very recent example, 13 SNPs previously identified in GWAS as associated with CHD/MI were incorporated into a multilocus model to estimate the association of a genetic risk score with incident CHD/MI in several large prospective studies. Even after adjusting for family history and traditional risk factors, individuals in the top quintile were at 1.66 times increased risk compared with those at the bottom quintile 36. There was a significant improvement in reclassification of intermediate risk patients. The use of these markers has not yet been shown to outperform models including traditional risk factors and family history. This shortcoming is probably because the vast majority of heritable risk remains undiscovered. The basis for this heritability gap remains unclear but is the focus of intense investigation. Despite the heritability gap, it is still possible that the use of known genetic risk factors may improve patient outcomes. For instance, genetic testing can improve patient adherence and risk factor reduction for Mendelian forms of coronary disease like familial hypercholesterolemia (FH). However, for "garden variety" coronary disease, there has never been a clinical trial that indicates that using genetic markers improves outcomes. There are strong signals from the NIH, the US Preventive Services Task Force and other independent prevention centers that genetic screening will be highly scrutinized until such trials exist. Currently, both the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group and the ACC/AHA Taskforce on Practice Guidelines recommend against genetic testing for coronary disease 39,40 because there is no clinical trial data supporting their use. Despite these recommendations, and lack of efficacy data, there are huge financial pressures to increase genetic testing by "direct-to-consumer" companies. In this context, there is a perfect opportunity to develop well-designed clinical trials to test these variants.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Disease
Keywords
genetic, atherosclerosis, myocardial infarction, risk, preventive cardiology
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
100 (Actual)
8. Arms, Groups, and Interventions
Arm Title
standard of care plus genetic information
Arm Type
Other
Arm Title
usual standard of care without genetic information
Arm Type
No Intervention
Intervention Type
Behavioral
Intervention Name(s)
genetic risk score for coronary risk factors
Intervention Description
genetic risk score based on coronary artery disease genetic risk variants (SNPs)
Primary Outcome Measure Information:
Title
change in LDL cholesterol
Time Frame
6 mo
Secondary Outcome Measure Information:
Title
change in weight
Time Frame
6 mo
Title
change in exercise
Time Frame
6 mo
Title
medication compliance
Time Frame
6 mo
Title
non-HDL cholesterol
Time Frame
6 mo
Title
blood pressure
Time Frame
6 mo
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Adults age > 18
Patient seeking cardiovascular risk evaluation
At intermediate (6-20%) or high risk (> 20%) over 10 years of CAD as defined by Framingham 10 year risk score AND/OR at > 20% risk of CAD over 30 years using the Framingham 30 year risk calculator
The genetic risk factors have been evaluated predominantly in white/European subjects. However, there is considerable overlap in the genetic architecture of South Asians and Hispanic/Latino populations. Therefore, we will limit our initial studies to these three race/ethnicity groups.
Exclusion Criteria:
History of myocardial infarction, angina, stroke, peripheral arterial disease, PCI, or CABG
Already on lipid lowering therapy
Anticipated survival <1 year (e.g. metastatic cancer)
Serious conditions that would limit ability to adhere to recommendations (inability to take statins, exercise)
Already had genetic testing
Concurrent enrollment in another clinical trial
Pregnant or breastfeeding
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joshua W. Knowles, MD-PhD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Themistocles L Assimes, MD-PhD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford Medical Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
22715281
Citation
Knowles JW, Assimes TL, Kiernan M, Pavlovic A, Goldstein BA, Yank V, McConnell MV, Absher D, Bustamante C, Ashley EA, Ioannidis JP. Randomized trial of personal genomics for preventive cardiology: design and challenges. Circ Cardiovasc Genet. 2012 Jun;5(3):368-76. doi: 10.1161/CIRCGENETICS.112.962746. No abstract available.
Results Reference
background
PubMed Identifier
28856136
Citation
Knowles JW, Zarafshar S, Pavlovic A, Goldstein BA, Tsai S, Li J, McConnell MV, Absher D, Ashley EA, Kiernan M, Ioannidis JPA, Assimes TL. Impact of a Genetic Risk Score for Coronary Artery Disease on Reducing Cardiovascular Risk: A Pilot Randomized Controlled Study. Front Cardiovasc Med. 2017 Aug 14;4:53. doi: 10.3389/fcvm.2017.00053. eCollection 2017.
Results Reference
result
Learn more about this trial
Personal Genomics for Preventive Cardiology
We'll reach out to this number within 24 hrs