Impact of Disclosing Coronary Artery Disease Polygenic Risk Score on Cardiovascular Health

NCT ID: NCT07087431

Last Updated: 2025-11-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-10-15
• Study Completion Date: 2027-08-15

Brief Summary

The goal of this clinical trial is to evaluate whether disclosure of a non-high polygenic risk score for coronary artery disease (CAD PRS) is non-inferior to standard of care in maintaining cardiovascular health over one year among adults aged 40-75 years without cardiovascular disease and not on statins.

Detailed Description

The main question PROACT 3 aims to answer is whether disclosure of a non-high CAD PRS result influences cardiovascular health behaviors and outcomes.

This is a single-center, randomized, non-inferiority trial of 400 adults aged 40-75 without cardiovascular disease and not on statins, identified through the Mass General Brigham primary care network. All participants will undergo CAD PRS testing, and those with non-high genetic risk will be randomized in a 1:1 ratio to receive immediate disclosure of their results or deferred disclosure after 12 months. The primary outcome is the change in cardiovascular health as measured by the American Heart Association's Life's Essential 8 (LE8) score from baseline to 12 months.

Secondary outcomes include engagement with preventive care, such as completion of lipid panels and blood pressure measurements, attendance at primary care visits, and initiation of preventive therapies (antihypertensive, lipid-lowering, or GLP-1 receptor agonist therapy or other anti-diabetic therapy) when clinically indicated. Additional outcomes will include changes in individual LE8 behavioral components (physical activity, diet, tobacco use, and sleep) and BMI from baseline to 12 months.

This trial is designed to address concerns about potential false reassurance from non-high CAD PRS disclosure and will provide empirical evidence to guide best practices for polygenic risk communication in preventive cardiology.

Conditions

Coronary Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Immediate Disclosure

Participants are randomized to receive their non-high CAD PRS immediately after genotyping.

Group Type: EXPERIMENTAL

Immediate disclosure of non-high CAD PRS

Intervention Type: BEHAVIORAL

Participants receive their non-high CAD PRS result as soon as it is available after genotyping.

Deferred Disclosure

Participants are randomized to have their non-high CAD PRS withheld for 12 months before receiving their result after the follow up period.

Group Type: ACTIVE_COMPARATOR

Deferred Disclosure of non-high CAD PRS

Intervention Type: BEHAVIORAL

Participants receive their non-high CAD PRS result after completion of the 12 month follow up period.

Interventions

Immediate disclosure of non-high CAD PRS

Participants receive their non-high CAD PRS result as soon as it is available after genotyping.

Intervention Type: BEHAVIORAL

Deferred Disclosure of non-high CAD PRS

Participants receive their non-high CAD PRS result after completion of the 12 month follow up period.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Current age 40-75 years
• Established primary care at Mass General Brigham with at least one visit in the last 2 years

Exclusion Criteria

• High CAD PRS
• Known cardiovascular disease, defined by a diagnosis of coronary artery disease, peripheral artery disease, or cerebrovascular disease
• Currently taking LDL cholesterol- lowering or anti-inflammatory medications, including statins or colchicine
• Liver disease (cirrhosis, active hepatitis, ALT > 3x ULN, total bilirubin > 2x ULN and not Gilbert's Syndrome)
• Contraindication to taking colchicine or rosuvastatin (allergy, liver or kidney disease)
• Pregnancy, breastfeeding, or planning to become pregnant during the study period
• Inability to provide informed consent
• Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m²
• BMI ≥ 40 kg/m²
• Inability to hold breath for 10 seconds

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Akl C. Fahed, MD, MPH

Interventional Cardiologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Roukoz Karam, MD

Role: CONTACT

proact@mgb.org

6174121147

Facility Contacts

Akl Fahed, MD, MPH

Role: primary

afahed@mgh.harvard.edu

6176434842

Other Identifiers

R01HL164629

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2025P001499

Identifier Type: -

Identifier Source: org_study_id