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Design of a randomized controlled trial of disclosing genomic risk of coronary heart disease: the Myocardial Infarction Genes (MI-GENES) study.

Kullo IJ, Jouni H, Olson JE, Montori VM, Bailey KR - BMC Med Genomics (2015)

Bottom Line: Whether disclosure of a genetic risk score (GRS) for a common disease influences relevant clinical outcomes is unknown.The study coordinator will obtain informed consent for the study that includes placing genetic testing results in the electronic health record.GRS, followed by shared decision making with a physician regarding statin use.

View Article: PubMed Central - PubMed

Affiliation: From the Division of Cardiovascular Diseases, Department of Medicine (IJK, HJ), Department of Health Sciences Research (JEO, KRB), Knowledge and Evaluation Research Unit (VMM), Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. Kullo.Iftikhar@mayo.edu.

ABSTRACT

Background: Whether disclosure of a genetic risk score (GRS) for a common disease influences relevant clinical outcomes is unknown. We describe design of the Myocardial Infarction Genes (MI-GENES) Study, a randomized clinical trial to assess whether disclosing a GRS for coronary heart disease (CHD) leads to lowering of low-density lipoprotein cholesterol (LDL-C) levels.

Methods and design: We performed an initial screening genotyping of 28 CHD susceptibility single-nucleotide polymorphisms (SNPs) that are not associated with blood pressure or lipid levels, in 1000 individuals from Olmsted County, Minnesota who were participants in the Mayo Clinic BioBank and met eligibility criteria. We calculated GRS based on 28 SNPs and will enroll 110 patients each in two CHD genomic risk categories: high (GRS ≥1.1), and average/low (GRS <1.1). The study coordinator will obtain informed consent for the study that includes placing genetic testing results in the electronic health record. Participants will undergo a blood draw and return 6-10 weeks later (Visit 2) once genotyping is completed and a GRS calculated. At this visit, patients will be randomized (1:1) to receive CHD risk estimates from a genetic counselor based on a conventional risk score (CRS) vs. GRS, followed by shared decision making with a physician regarding statin use. Three and six months following the disclosure of CHD risk, participants will return for measurement of fasting lipid levels and assessment of changes in dietary fat intake and physical activity levels. Psychosocial measures will be assessed at baseline and after disclosure of CHD risk.

Discussion: The proposed trial will provide insights into the clinical utility of genetic testing for CHD risk assessment.

Clinical trial registration: ClinicalTrials.gov registration number: NCT01936675 .

No MeSH data available.


Related in: MedlinePlus

Flow Diagram of the Proposed Clinical Trial. A flow diagram illustrating the design of the MI-GENES study. A total of 2026 individuals from the Mayo BioBank met the eligibility criteria. Among those 2026, a random sample of 1000 individuals was sent for screening genotyping. A total of 968 individuals had valid screening genotyping results. Recruitment was based on screening genotyping results in order to achieve the targeted enrollment goals of ~110 individuals with high GRS (≥1.1) and ~110 with average/low GRS (<1.1) with the expectation that approximately 10-20 study participants are likely to withdraw from the study or be lost to follow-up
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Fig1: Flow Diagram of the Proposed Clinical Trial. A flow diagram illustrating the design of the MI-GENES study. A total of 2026 individuals from the Mayo BioBank met the eligibility criteria. Among those 2026, a random sample of 1000 individuals was sent for screening genotyping. A total of 968 individuals had valid screening genotyping results. Recruitment was based on screening genotyping results in order to achieve the targeted enrollment goals of ~110 individuals with high GRS (≥1.1) and ~110 with average/low GRS (<1.1) with the expectation that approximately 10-20 study participants are likely to withdraw from the study or be lost to follow-up

Mentions: To maximize information yield from the study, we performed an initial screening genotyping of 28 CHD susceptibility SNPs that are not associated with blood pressure (BP) or lipid levels, in 1000 individuals from Olmsted County who were participants in the Mayo Clinic BioBank and met the eligibility criteria. We calculated GRS for each individual based on these 28 SNPs and stratified individuals into two CHD genomic risk categories: high (GRS ≥1.1), and average/low (GRS <1.1). We will enroll 110 patients in each of the two categories for the clinical trial (Fig. 1). The study coordinator will invite these patients by phone to participate in the randomized trial. He/she will inform patients about the trial, confirm eligibility, and subsequently obtain written informed consent. Specifically, the study coordinator will describe the limitations of genetic testing, the unclear medical benefit of such testing, the format for disclosure of risk, and that the results will be placed in the EHR.


Design of a randomized controlled trial of disclosing genomic risk of coronary heart disease: the Myocardial Infarction Genes (MI-GENES) study.

Kullo IJ, Jouni H, Olson JE, Montori VM, Bailey KR - BMC Med Genomics (2015)

Flow Diagram of the Proposed Clinical Trial. A flow diagram illustrating the design of the MI-GENES study. A total of 2026 individuals from the Mayo BioBank met the eligibility criteria. Among those 2026, a random sample of 1000 individuals was sent for screening genotyping. A total of 968 individuals had valid screening genotyping results. Recruitment was based on screening genotyping results in order to achieve the targeted enrollment goals of ~110 individuals with high GRS (≥1.1) and ~110 with average/low GRS (<1.1) with the expectation that approximately 10-20 study participants are likely to withdraw from the study or be lost to follow-up
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4536729&req=5

Fig1: Flow Diagram of the Proposed Clinical Trial. A flow diagram illustrating the design of the MI-GENES study. A total of 2026 individuals from the Mayo BioBank met the eligibility criteria. Among those 2026, a random sample of 1000 individuals was sent for screening genotyping. A total of 968 individuals had valid screening genotyping results. Recruitment was based on screening genotyping results in order to achieve the targeted enrollment goals of ~110 individuals with high GRS (≥1.1) and ~110 with average/low GRS (<1.1) with the expectation that approximately 10-20 study participants are likely to withdraw from the study or be lost to follow-up
Mentions: To maximize information yield from the study, we performed an initial screening genotyping of 28 CHD susceptibility SNPs that are not associated with blood pressure (BP) or lipid levels, in 1000 individuals from Olmsted County who were participants in the Mayo Clinic BioBank and met the eligibility criteria. We calculated GRS for each individual based on these 28 SNPs and stratified individuals into two CHD genomic risk categories: high (GRS ≥1.1), and average/low (GRS <1.1). We will enroll 110 patients in each of the two categories for the clinical trial (Fig. 1). The study coordinator will invite these patients by phone to participate in the randomized trial. He/she will inform patients about the trial, confirm eligibility, and subsequently obtain written informed consent. Specifically, the study coordinator will describe the limitations of genetic testing, the unclear medical benefit of such testing, the format for disclosure of risk, and that the results will be placed in the EHR.

Bottom Line: Whether disclosure of a genetic risk score (GRS) for a common disease influences relevant clinical outcomes is unknown.The study coordinator will obtain informed consent for the study that includes placing genetic testing results in the electronic health record.GRS, followed by shared decision making with a physician regarding statin use.

View Article: PubMed Central - PubMed

Affiliation: From the Division of Cardiovascular Diseases, Department of Medicine (IJK, HJ), Department of Health Sciences Research (JEO, KRB), Knowledge and Evaluation Research Unit (VMM), Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. Kullo.Iftikhar@mayo.edu.

ABSTRACT

Background: Whether disclosure of a genetic risk score (GRS) for a common disease influences relevant clinical outcomes is unknown. We describe design of the Myocardial Infarction Genes (MI-GENES) Study, a randomized clinical trial to assess whether disclosing a GRS for coronary heart disease (CHD) leads to lowering of low-density lipoprotein cholesterol (LDL-C) levels.

Methods and design: We performed an initial screening genotyping of 28 CHD susceptibility single-nucleotide polymorphisms (SNPs) that are not associated with blood pressure or lipid levels, in 1000 individuals from Olmsted County, Minnesota who were participants in the Mayo Clinic BioBank and met eligibility criteria. We calculated GRS based on 28 SNPs and will enroll 110 patients each in two CHD genomic risk categories: high (GRS ≥1.1), and average/low (GRS <1.1). The study coordinator will obtain informed consent for the study that includes placing genetic testing results in the electronic health record. Participants will undergo a blood draw and return 6-10 weeks later (Visit 2) once genotyping is completed and a GRS calculated. At this visit, patients will be randomized (1:1) to receive CHD risk estimates from a genetic counselor based on a conventional risk score (CRS) vs. GRS, followed by shared decision making with a physician regarding statin use. Three and six months following the disclosure of CHD risk, participants will return for measurement of fasting lipid levels and assessment of changes in dietary fat intake and physical activity levels. Psychosocial measures will be assessed at baseline and after disclosure of CHD risk.

Discussion: The proposed trial will provide insights into the clinical utility of genetic testing for CHD risk assessment.

Clinical trial registration: ClinicalTrials.gov registration number: NCT01936675 .

No MeSH data available.


Related in: MedlinePlus