Coronary Artery DiseaseGenoVANCT04331535
The Genomic Medicine at VA Study
A study testing Polygenic risk score (PRS) in people with Coronary Artery Disease and Atrial Fibrillation, run by Boston VA Research Institute, Inc. at 1 site in United States.
Trial summary
This trial will determine the clinical effectiveness of polygenic risk score testing among patients at high genetic risk for at least one of six diseases (coronary artery disease, atrial fibrillation, type 2 diabetes mellitus, colorectal cancer, breast cancer, or prostate cancer), measured by time-to-diagnosis of… Read more about this study
- Who is it for?
- Ages 50 to 70 years
- Conditions the study is for
- Coronary Artery Disease, Atrial Fibrillation, Type 2 Diabetes
- What is being tested?
- Polygenic risk score (PRS)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,071 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Jul 2020to 30 Sep 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 50-70 years at enrollment
- No known diagnosis of the following conditions, initially screened by the International Classification of Disease (ICD) codes or other electronic health record (EHR) data using validated methods and then confirmed with potential patient-participants during recruitment: coronary artery disease, atrial fibrillation, type 2 diabetes, colorectal cancer, breast cancer, prostate cancer
Who cannot join
- Patients will be ineligible if they:
- Have a known diagnosis of at least one of the six diseases of interest
- Are younger than age 50 or older than age 70
- Are pregnant
- Are incarcerated or institutionalized
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Boston Healthcare System
Boston, Massachusetts, 02130-4817
About this study
Official title: Pragmatic Randomized Trial of Polygenic Risk Scoring for Common Diseases in Primary Care
This trial will determine the clinical effectiveness of polygenic risk score testing among patients at high genetic risk for at least one of six diseases (coronary artery disease, atrial fibrillation, type 2 diabetes mellitus, colorectal cancer, breast cancer, or prostate cancer), measured by time-to-diagnosis of prevalent or incident disease over 24 months.
Read the detailed description
One of the most pressing controversies in genomics today is the clinical utility of polygenic risk scores (PRS). Broadening the scope of genomic risk testing beyond monogenic diseases, PRS combine information from hundreds or even millions of genetic loci, each with a very small effect size on the risk of common complex disease. The result is a continuous quantitative risk factor for susceptibility to conditions such as coronary artery disease (CAD), type 2 diabetes (T2D), and breast cancer. Compared to rarer monogenic disease variants, PRS have greater transformative potential for public health and healthcare in their ability to identify much larger proportions of the population at significantly elevated risk for disease, facilitating evidence-based prevention and management. Moreover, their prediction ability has vastly improved compared to earlier PRS that included only a limited number of genetic variants. However, while the associations between PRS and a wide range of common diseases are well established (clinical validity), the potential impact of this information on patient health outcomes (clinical utility) remains contested and understudied.
This study will examine the effectiveness and implementation outcomes from the use of PRS for 6 common diseases that are screened for by PCPs and have established prevention strategies: CAD, AFib, T2D, colorectal cancer, prostate cancer, and breast cancer. This trial has two aims:
Aim 1: Conduct a randomized controlled trial (RCT) to determine the clinical effectiveness of PRS among patients at high genetic risk for at least one disease, measured by changes in clinical management (process outcomes) and time to diagnosis of prevalent or incident disease (clinical outcome) over 24 months.
Aim 2: Measure high-priority genomic medicine implementation outcomes, including primary care provider (PCP) knowledge and beliefs about PRS, patient activation in healthcare, medication adherence, and costs.
- Conditions
- Coronary Artery Disease, Atrial Fibrillation, Type 2 Diabetes, Colorectal Cancer, Breast Cancer, Prostate Cancer
- Being tested
- Polygenic risk score (PRS)
- Keywords
- Polygenic risk score, Coronary artery disease, Atrial fibrillation, Type 2 diabetes, Colorectal cancer, Breast cancer, Prostate cancer
- Medical subject headings
- Coronary Artery Disease, Atrial Fibrillation, Diabetes Mellitus, Type 2, Colorectal Neoplasms, Breast Neoplasms, Prostatic Neoplasms, Genetic Risk Score
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Polygenic risk score (PRS)Diagnostic test
Polygenic risk score report from a Clinical Laboratory Improvement Amendment (CLIA)-certified laboratory for coronary artery disease, atrial fibrillation, type 2 diabetes, colorectal cancer, breast cancer (for women only), and prostate cancer (for men only), delivered along with patient- and provider-level educational material.
| Study group | Role | What they receive |
|---|---|---|
| Polygenic risk score (PRS) - high risk stratum | Experimental | Patient-participants in the PRS-high arm and their providers will receive their high-PRS results at baseline, along with educational resources about the results. Receives: Diagnostic Test: Polygenic risk score (PRS) |
| Usual care (UC) - high risk stratum | Active comparator | Patient-participants in the UC-high arm and their providers will receive their high-PRS results after a 24-month observation period, along with educational resources about the results. Receives: Diagnostic Test: Polygenic risk score (PRS) |
| Polygenic risk score (PRS) - average risk stratum | Experimental | Patient-participants in the PRS-average arm and their providers will receive their average-PRS results at baseline, along with educational resources about the results. Receives: Diagnostic Test: Polygenic risk score (PRS) |
| Usual care (UC) - average risk stratum | Active comparator | Patient-participants in the UC-average arm and their providers will receive their average-PRS results after a 24-month observation period, along with educational resources about the results.. Receives: Diagnostic Test: Polygenic risk score (PRS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time-to-new diagnosis of common complex disease
The primary outcome of the study is time-to-diagnosis both of undiagnosed prevalent cases of the 6 target conditions and incident cases during the study period. This composite outcome will only include clinically significant diagnoses, as adjudicated by expert clinical chart review.
Measured: 24 months after enrollment
Secondary outcomes (4)
Diagnostic testing
Any evidence that the patient-participant underwent additional diagnostic testing for the six target diseases since enrollment: coronary artery disease (stress testing, cardiac CT for coronary artery calcium (CAC), coronary angiography), atrial fibrillation (ECG, heart rhythm monitoring), type 2 diabetes (hemoglobin A1c, blood glucose), colorectal cancer (colonoscopy, sigmoidoscopy, fecal blood testing, CT colonography), breast cancer (mammography, breast MRI, breast ultrasound, breast biopsy), and prostate cancer (PSA testing, prostate biopsy).
Measured: 24 months after enrollment
Patient activation
Self-reported understanding, competence, and willingness to participate health care decisions and processes assessed on the baseline and end-of-study surveys, using the 13-item short form of the Patient Activation Measure (Hibbard, Health Services Research 2005).
Measured: Baseline and 24 months after enrollment
Healthcare costs
A combination of administrative data and microcosting approaches will be used to estimate the costs of the intervention and the subsequent patient-level healthcare costs over the 24 months after enrollment. Estimates of the infrastructure and personnel needed to deliver the intervention will be derived empirically from the study. Healthcare costs will be abstracted from billing and administrative data.
Measured: 24 months after enrollment
Medication adherence
Self-report of taking medications as prescribed assessed on the baseline and end-of-study surveys, using the 3-item Voils Medication Adherence Survey (Voils, Medical Care, 2012).
Measured: Baseline and 24 months after enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2020
- Study start17 Jul 2020
- Primary completion31 Jan 2026
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (152)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized clinical trial comparing polygenic risk score (PRS) testing and reporting to delayed reporting
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 1,071 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston VA Research Institute, Inc.
- Sponsor type
- University, hospital or other
- Collaborators
- VA Boston Healthcare System
- Responsible party
- Principal investigator, Jason Vassy, Harvard Medical School (HMS and HSDM)
- Investigators
- Jason L. Vassy, MD, MPH, SM, Principal investigator, Harvard Medical School (HMS and HSDM)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04331535
- Sponsor's protocol ID
- 0594
- Acronym
- GenoVA
- Status last verified
- Oct 2026
- First submitted
- 31 Mar 2020
- Last updated
- 2 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: We will share de-identified individual-level trial data through a data repository housed on a secure VA server and accessible only to outside investigators with Institutional Review Board (IRB).
Publications
Chatterjee N, Shi J, Garcia-Closas M. Developing and evaluating polygenic risk prediction models for stratified disease prevention. Nat Rev Genet. 2016 Jul;17(7):392-406. doi: 10.1038/nrg.2016.27. Epub 2016 May 3.
PubMed 27140283Dudbridge F. Polygenic Epidemiology. Genet Epidemiol. 2016 May;40(4):268-72. doi: 10.1002/gepi.21966. Epub 2016 Apr 7.
PubMed 27061411Kotze MJ, Luckhoff HK, Peeters AV, Baatjes K, Schoeman M, van der Merwe L, Grant KA, Fisher LR, van der Merwe N, Pretorius J, van Velden DP, Myburgh EJ, Pienaar FM, van Rensburg SJ, Yako YY, September AV, Moremi KE, Cronje FJ, Tiffin N, Bouwens CS, Bezuidenhout J, Apffelstaedt JP, Hough FS, Erasmus RT, Schneider JW. Genomic medicine and risk prediction across the disease spectrum. Crit Rev Clin Lab Sci. 2015;52(3):120-37. doi: 10.3109/10408363.2014.997930. Epub 2015 Jan 19.
PubMed 25597499Schork AJ, Schork MA, Schork NJ. Genetic risks and clinical rewards. Nat Genet. 2018 Sep;50(9):1210-1211. doi: 10.1038/s41588-018-0213-x. No abstract available.
PubMed 30158681Torkamani A, Wineinger NE, Topol EJ. The personal and clinical utility of polygenic risk scores. Nat Rev Genet. 2018 Sep;19(9):581-590. doi: 10.1038/s41576-018-0018-x.
PubMed 29789686Knowles JW, Ashley EA. Cardiovascular disease: The rise of the genetic risk score. PLoS Med. 2018 Mar 30;15(3):e1002546. doi: 10.1371/journal.pmed.1002546. eCollection 2018 Mar.
PubMed 29601582Khera AV, Chaffin M, Aragam KG, Haas ME, Roselli C, Choi SH, Natarajan P, Lander ES, Lubitz SA, Ellinor PT, Kathiresan S. Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat Genet. 2018 Sep;50(9):1219-1224. doi: 10.1038/s41588-018-0183-z. Epub 2018 Aug 13.
PubMed 30104762Fuchsberger C, Flannick J, Teslovich TM, Mahajan A, Agarwala V, Gaulton KJ, Ma C, Fontanillas P, Moutsianas L, McCarthy DJ, Rivas MA, Perry JRB, Sim X, Blackwell TW, Robertson NR, Rayner NW, Cingolani P, Locke AE, Tajes JF, Highland HM, Dupuis J, Chines PS, Lindgren CM, Hartl C, Jackson AU, Chen H, Huyghe JR, van de Bunt M, Pearson RD, Kumar A, Muller-Nurasyid M, Grarup N, Stringham HM, Gamazon ER, Lee J, Chen Y, Scott RA, Below JE, Chen P, Huang J, Go MJ, Stitzel ML, Pasko D, Parker SCJ, Varga TV, Green T, Beer NL, Day-Williams AG, Ferreira T, Fingerlin T, Horikoshi M, Hu C, Huh I, Ikram MK, Kim BJ, Kim Y, Kim YJ, Kwon MS, Lee J, Lee S, Lin KH, Maxwell TJ, Nagai Y, Wang X, Welch RP, Yoon J, Zhang W, Barzilai N, Voight BF, Han BG, Jenkinson CP, Kuulasmaa T, Kuusisto J, Manning A, Ng MCY, Palmer ND, Balkau B, Stancakova A, Abboud HE, Boeing H, Giedraitis V, Prabhakaran D, Gottesman O, Scott J, Carey J, Kwan P, Grant G, Smith JD, Neale BM, Purcell S, Butterworth AS, Howson JMM, Lee HM, Lu Y, Kwak SH, Zhao W, Danesh J, Lam VKL, Park KS, Saleheen D, So WY, Tam CHT, Afzal U, Aguilar D, Arya R, Aung T, Chan E, Navarro C, Cheng CY, Palli D, Correa A, Curran JE, Rybin D, Farook VS, Fowler SP, Freedman BI, Griswold M, Hale DE, Hicks PJ, Khor CC, Kumar S, Lehne B, Thuillier D, Lim WY, Liu J, van der Schouw YT, Loh M, Musani SK, Puppala S, Scott WR, Yengo L, Tan ST, Taylor HA Jr, Thameem F, Wilson G Sr, Wong TY, Njolstad PR, Levy JC, Mangino M, Bonnycastle LL, Schwarzmayr T, Fadista J, Surdulescu GL, Herder C, Groves CJ, Wieland T, Bork-Jensen J, Brandslund I, Christensen C, Koistinen HA, Doney ASF, Kinnunen L, Esko T, Farmer AJ, Hakaste L, Hodgkiss D, Kravic J, Lyssenko V, Hollensted M, Jorgensen ME, Jorgensen T, Ladenvall C, Justesen JM, Karajamaki A, Kriebel J, Rathmann W, Lannfelt L, Lauritzen T, Narisu N, Linneberg A, Melander O, Milani L, Neville M, Orho-Melander M, Qi L, Qi Q, Roden M, Rolandsson O, Swift A, Rosengren AH, Stirrups K, Wood AR, Mihailov E, Blancher C, Carneiro MO, Maguire J, Poplin R, Shakir K, Fennell T, DePristo M, de Angelis MH, Deloukas P, Gjesing AP, Jun G, Nilsson P, Murphy J, Onofrio R, Thorand B, Hansen T, Meisinger C, Hu FB, Isomaa B, Karpe F, Liang L, Peters A, Huth C, O'Rahilly SP, Palmer CNA, Pedersen O, Rauramaa R, Tuomilehto J, Salomaa V, Watanabe RM, Syvanen AC, Bergman RN, Bharadwaj D, Bottinger EP, Cho YS, Chandak GR, Chan JCN, Chia KS, Daly MJ, Ebrahim SB, Langenberg C, Elliott P, Jablonski KA, Lehman DM, Jia W, Ma RCW, Pollin TI, Sandhu M, Tandon N, Froguel P, Barroso I, Teo YY, Zeggini E, Loos RJF, Small KS, Ried JS, DeFronzo RA, Grallert H, Glaser B, Metspalu A, Wareham NJ, Walker M, Banks E, Gieger C, Ingelsson E, Im HK, Illig T, Franks PW, Buck G, Trakalo J, Buck D, Prokopenko I, Magi R, Lind L, Farjoun Y, Owen KR, Gloyn AL, Strauch K, Tuomi T, Kooner JS, Lee JY, Park T, Donnelly P, Morris AD, Hattersley AT, Bowden DW, Collins FS, Atzmon G, Chambers JC, Spector TD, Laakso M, Strom TM, Bell GI, Blangero J, Duggirala R, Tai ES, McVean G, Hanis CL, Wilson JG, Seielstad M, Frayling TM, Meigs JB, Cox NJ, Sladek R, Lander ES, Gabriel S, Burtt NP, Mohlke KL, Meitinger T, Groop L, Abecasis G, Florez JC, Scott LJ, Morris AP, Kang HM, Boehnke M, Altshuler D, McCarthy MI. The genetic architecture of type 2 diabetes. Nature. 2016 Aug 4;536(7614):41-47. doi: 10.1038/nature18642. Epub 2016 Jul 11.
PubMed 27398621Gibson G. Rare and common variants: twenty arguments. Nat Rev Genet. 2012 Jan 18;13(2):135-45. doi: 10.1038/nrg3118.
PubMed 22251874Golan D, Lander ES, Rosset S. Measuring missing heritability: inferring the contribution of common variants. Proc Natl Acad Sci U S A. 2014 Dec 9;111(49):E5272-81. doi: 10.1073/pnas.1419064111. Epub 2014 Nov 24.
PubMed 25422463Barton NH, Etheridge AM, Veber A. The infinitesimal model: Definition, derivation, and implications. Theor Popul Biol. 2017 Dec;118:50-73. doi: 10.1016/j.tpb.2017.06.001. Epub 2017 Jul 11.
PubMed 28709925Boyle EA, Li YI, Pritchard JK. An Expanded View of Complex Traits: From Polygenic to Omnigenic. Cell. 2017 Jun 15;169(7):1177-1186. doi: 10.1016/j.cell.2017.05.038.
PubMed 28622505Khoury MJ, Janssens AC, Ransohoff DF. How can polygenic inheritance be used in population screening for common diseases? Genet Med. 2013 Jun;15(6):437-43. doi: 10.1038/gim.2012.182. Epub 2013 Feb 14.
PubMed 23412608Warren M. The approach to predictive medicine that is taking genomics research by storm. Nature. 2018 Oct;562(7726):181-183. doi: 10.1038/d41586-018-06956-3. No abstract available.
PubMed 30305759Inouye M, Abraham G, Nelson CP, Wood AM, Sweeting MJ, Dudbridge F, Lai FY, Kaptoge S, Brozynska M, Wang T, Ye S, Webb TR, Rutter MK, Tzoulaki I, Patel RS, Loos RJF, Keavney B, Hemingway H, Thompson J, Watkins H, Deloukas P, Di Angelantonio E, Butterworth AS, Danesh J, Samani NJ; UK Biobank CardioMetabolic Consortium CHD Working Group. Genomic Risk Prediction of Coronary Artery Disease in 480,000 Adults: Implications for Primary Prevention. J Am Coll Cardiol. 2018 Oct 16;72(16):1883-1893. doi: 10.1016/j.jacc.2018.07.079.
PubMed 30309464
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pragmatic Randomized Trial of Polygenic Risk Scoring for Common Diseases in Primary Care
- ClinicalTrials.gov ID
- NCT04331535
- Acronym / sponsor ID
- GenoVA / 0594
- Conditions
- Coronary Artery Disease, Atrial Fibrillation, Type 2 Diabetes, Colorectal Cancer, Breast Cancer, Prostate Cancer
- Keywords
- Polygenic risk score, Coronary artery disease, Atrial fibrillation, Type 2 diabetes, Colorectal cancer, Breast cancer, Prostate cancer
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 1,071 participants (actual)
- Lead sponsor
- Boston VA Research Institute, Inc.University, hospital or other
- Collaborators
- VA Boston Healthcare System
- Study start
- 17 Jul 2020 (actual)
- Primary completion
- 31 Jan 2026 (actual)
- Study completion
- 30 Sep 2027 (estimated)
- First posted
- 2 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial will determine the clinical effectiveness of polygenic risk score testing among patients at high genetic risk for at least one of six diseases (coronary artery disease, atrial fibrillation, type 2 diabetes mellitus, colorectal cancer, breast cancer, or prostate cancer), measured by time-to-diagnosis of prevalent or incident disease over 24 months.
Detailed description
One of the most pressing controversies in genomics today is the clinical utility of polygenic risk scores (PRS). Broadening the scope of genomic risk testing beyond monogenic diseases, PRS combine information from hundreds or even millions of genetic loci, each with a very small effect size on the risk of common complex disease. The result is a continuous quantitative risk factor for susceptibility to conditions such as coronary artery disease (CAD), type 2 diabetes (T2D), and breast cancer. Compared to rarer monogenic disease variants, PRS have greater transformative potential for public health and healthcare in their ability to identify much larger proportions of the population at significantly elevated risk for disease, facilitating evidence-based prevention and management. Moreover, their prediction ability has vastly improved compared to earlier PRS that included only a limited number of genetic variants. However, while the associations between PRS and a wide range of common diseases are well established (clinical validity), the potential impact of this information on patient health outcomes (clinical utility) remains contested and understudied.
This study will examine the effectiveness and implementation outcomes from the use of PRS for 6 common diseases that are screened for by PCPs and have established prevention strategies: CAD, AFib, T2D, colorectal cancer, prostate cancer, and breast cancer. This trial has two aims:
Aim 1: Conduct a randomized controlled trial (RCT) to determine the clinical effectiveness of PRS among patients at high genetic risk for at least one disease, measured by changes in clinical management (process outcomes) and time to diagnosis of prevalent or incident disease (clinical outcome) over 24 months.
Aim 2: Measure high-priority genomic medicine implementation outcomes, including primary care provider (PCP) knowledge and beliefs about PRS, patient activation in healthcare, medication adherence, and costs.
Study design
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 4
- Model description
- Randomized clinical trial comparing polygenic risk score (PRS) testing and reporting to delayed reporting
| Arm | Type | Receives |
|---|---|---|
| Polygenic risk score (PRS) - high risk stratum | Experimental | Diagnostic Test: Polygenic risk score (PRS)Patient-participants in the PRS-high arm and their providers will receive their high-PRS results at baseline, along with educational resources about the results. |
| Usual care (UC) - high risk stratum | Active comparator | Diagnostic Test: Polygenic risk score (PRS)Patient-participants in the UC-high arm and their providers will receive their high-PRS results after a 24-month observation period, along with educational resources about the results. |
| Polygenic risk score (PRS) - average risk stratum | Experimental | Diagnostic Test: Polygenic risk score (PRS)Patient-participants in the PRS-average arm and their providers will receive their average-PRS results at baseline, along with educational resources about the results. |
| Usual care (UC) - average risk stratum | Active comparator | Diagnostic Test: Polygenic risk score (PRS)Patient-participants in the UC-average arm and their providers will receive their average-PRS results after a 24-month observation period, along with educational resources about the results.. |
Who may qualify
- Ages
- 50 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Age 50-70 years at enrollment
- No known diagnosis of the following conditions, initially screened by the International Classification of Disease (ICD) codes or other electronic health record (EHR) data using validated methods and then confirmed with potential patient-participants during recruitment: coronary artery disease, atrial fibrillation, type 2 diabetes, colorectal cancer, breast cancer, prostate cancer
Key exclusion criteria (5 listed)
- Patients will be ineligible if they:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Polygenic risk score (PRS)Polygenic risk score report from a Clinical Laboratory Improvement Amendment (CLIA)-certified laboratory for coronary artery disease, atrial fibrillation, type 2 diabetes, colorectal cancer, breast cancer (for women only), and prostate cancer (for men only), delivered along with patient- and provider-level educational material. | Diagnostic test | Polygenic risk score (PRS) - average risk stratum, Polygenic risk score (PRS) - high risk stratum, Usual care (UC) - average risk stratum, Usual care (UC) - high risk stratum |
Primary outcome
Time-to-new diagnosis of common complex disease
Time frame: 24 months after enrollment
The primary outcome of the study is time-to-diagnosis both of undiagnosed prevalent cases of the 6 target conditions and incident cases during the study period. This composite outcome will only include clinically significant diagnoses, as adjudicated by expert clinical chart review.
4 secondary outcomes
Diagnostic testing
Time frame: 24 months after enrollment
Patient activation
Time frame: Baseline and 24 months after enrollment
Healthcare costs
Time frame: 24 months after enrollment
Medication adherence
Time frame: Baseline and 24 months after enrollment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2026.
- Background: PubMed 27140283Chatterjee N, Shi J, Garcia-Closas M. Developing and evaluating polygenic risk prediction models for stratified disease prevention. Nat Rev Genet. 2016 Jul;17(7):392-406. doi: 10.1038/nrg.2016.27. Epub 2016 May 3.
- Background: PubMed 27061411Dudbridge F. Polygenic Epidemiology. Genet Epidemiol. 2016 May;40(4):268-72. doi: 10.1002/gepi.21966. Epub 2016 Apr 7.
- Background: PubMed 25597499Kotze MJ, Luckhoff HK, Peeters AV, Baatjes K, Schoeman M, van der Merwe L, Grant KA, Fisher LR, van der Merwe N, Pretorius J, van Velden DP, Myburgh EJ, Pienaar FM, van Rensburg SJ, Yako YY, September AV, Moremi KE, Cronje FJ, Tiffin N, Bouwens CS, Bezuidenhout J, Apffelstaedt JP, Hough FS, Erasmus RT, Schneider JW. Genomic medicine and risk prediction across the disease spectrum. Crit Rev Clin Lab Sci. 2015;52(3):120-37. doi: 10.3109/10408363.2014.997930. Epub 2015 Jan 19.
- Background: PubMed 30158681Schork AJ, Schork MA, Schork NJ. Genetic risks and clinical rewards. Nat Genet. 2018 Sep;50(9):1210-1211. doi: 10.1038/s41588-018-0213-x. No abstract available.
- Background: PubMed 29789686Torkamani A, Wineinger NE, Topol EJ. The personal and clinical utility of polygenic risk scores. Nat Rev Genet. 2018 Sep;19(9):581-590. doi: 10.1038/s41576-018-0018-x.
- Background: PubMed 29601582Knowles JW, Ashley EA. Cardiovascular disease: The rise of the genetic risk score. PLoS Med. 2018 Mar 30;15(3):e1002546. doi: 10.1371/journal.pmed.1002546. eCollection 2018 Mar.
- Background: PubMed 30104762Khera AV, Chaffin M, Aragam KG, Haas ME, Roselli C, Choi SH, Natarajan P, Lander ES, Lubitz SA, Ellinor PT, Kathiresan S. Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat Genet. 2018 Sep;50(9):1219-1224. doi: 10.1038/s41588-018-0183-z. Epub 2018 Aug 13.
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- This link references a poster presentation at the annual American Medical Informatics Association (AMIA) in 2017 by authors Majahalme N, Miller SJ, Zimolzak AJ, and Vassy JL.Link provided by the sponsor.
- This link references the National Veterans Health Equity report for FY2013, published by the VA Office of Health Equity.Link provided by the sponsor.
- This link references the Surveillance, Epidemiology, and End Results (SEER) database from November 2017, published by the NIH.Link provided by the sponsor.
- This link references the National Diabetes Statistics Report from 2017, published by the Centers for Disease Control and Prevention (CDC).Link provided by the sponsor.
- This link references a book entitled "Systematic Methods for Collecting and Analyzing Multidisciplinary Team Based Qualitative Data," authored by Carey JW and Gelaude D.Link provided by the sponsor.
- This link references a book entitled "Applied Thematic Analysis," authored by Guest GS, MacQueen KM, and Namey EE.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. We will share de-identified individual-level trial data through a data repository housed on a secure VA server and accessible only to outside investigators with Institutional Review Board (IRB).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jason L. Vassy, MD, MPH, SM principal investigator
Harvard Medical School (HMS and HSDM)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Polygenic risk score (PRS) in people with Coronary Artery Disease and Atrial Fibrillation, run by Boston VA Research Institute, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 2 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time-to-new diagnosis of common complex disease (time frame: 24 months after enrollment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04331535, which also lists 152 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2026.