Personal Genomics for Preventive Cardiology

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Stanford University
ClinicalTrials.gov Identifier:
NCT01406808
First received: July 28, 2011
Last updated: January 7, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention
Coronary Artery Disease
Behavioral: genetic risk score for coronary risk factors

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Pilot Randomized Trial of Personal Genomics for Preventive Cardiology

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • change in LDL cholesterol [ Time Frame: 6 mo ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • change in weight [ Time Frame: 6 mo ] [ Designated as safety issue: No ]
  • change in exercise [ Time Frame: 6 mo ] [ Designated as safety issue: No ]
  • medication compliance [ Time Frame: 6 mo ] [ Designated as safety issue: No ]
  • non-HDL cholesterol [ Time Frame: 6 mo ] [ Designated as safety issue: No ]
  • blood pressure [ Time Frame: 6 mo ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: August 2011
Estimated Study Completion Date: January 2014
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
standard of care plus genetic information Behavioral: genetic risk score for coronary risk factors
genetic risk score based on coronary artery disease genetic risk variants (SNPs)
No Intervention: usual standard of care without genetic information

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01406808

Locations
United States, California
Stanford Medical Center
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Investigators
Principal Investigator: Joshua W. Knowles, MD-PhD Stanford University
Principal Investigator: Themistocles L Assimes, MD-PhD Stanford University
  More Information

No publications provided by Stanford University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Stanford University
ClinicalTrials.gov Identifier: NCT01406808     History of Changes
Other Study ID Numbers: SU-07272011-8149
Study First Received: July 28, 2011
Last Updated: January 7, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Stanford University:
genetic
atherosclerosis
myocardial infarction
risk
preventive cardiology

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on August 20, 2014