NCT04331535

The Genomic Medicine at VA Study

Pragmatic Randomized Trial of Polygenic Risk Scoring for Common Diseases in Primary Care

• Status: Unknown
• Phase: N/A
• Study type: Interventional
• Enrollment: 1,076 (estimated)
• Sponsor: Boston VA Research Institute, Inc. · Academic / Other
• Sex: All
• Age: 50 Years – 70 Years
• Healthy volunteers: Not accepted

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 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.

Conditions

• Coronary Artery Disease
• Atrial Fibrillation
• Type 2 Diabetes
• Colorectal Cancer
• Breast Cancer
• Prostate Cancer

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	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.

Timeline

• Start date: 2020-07-17
• Primary completion: 2025-09-30
• Completion: 2025-09-30
• First posted: 2020-04-02
• Last updated: 2022-10-03

Locations

1 site across 1 country: United States