Polygenic Risk-based Detection of Subclinical Coronary Atherosclerosis and Change in Cardiovascular Health

NCT ID: NCT05819814

Last Updated: 2025-07-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-07
• Study Completion Date: 2027-02-01

Brief Summary

The goal of this randomized controlled trial is to assess the impact of disclosing a high polygenic risk result for coronary artery disease on change in cardiovascular health over one year.

Detailed Description

The main question PROACT 1 aims to answer is whether cardiovascular health improves following disclosure of high polygenic risk result for coronary artery disease compared to standard of care.

This is a 1:1 randomized controlled trial of middle-aged participants with no known cardiovascular disease, are not on lipid-lowering therapy, who have high polygenic risk score for coronary artery disease, and do not have quantifiable plaque on coronary computed tomography angiography. Participants will be randomized into two equal groups: one group will receive their high polygenic risk result for coronary artery disease at baseline, and the other group will receive their result after study completion at 1 year. Change in cardiovascular health as measured by the American Heart Association Life's Essential 8 score from baseline to one-year will be compared.

Conditions

Coronary Artery Disease

Study Design

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

Study Groups

Intervention

Participants will receive their high polygenic risk result for coronary artery disease.

Group Type: EXPERIMENTAL

Disclosure of high polygenic risk result for coronary artery disease

Intervention Type: GENETIC

The disclosure of a high polygenic risk result for coronary artery disease involves a clinical report coupled with a virtual meeting with a genetic counselor.

Control

Participants will receive standard of care, and disclosure of high polygenic risk result will be deferred until study completion.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Disclosure of high polygenic risk result for coronary artery disease

The disclosure of a high polygenic risk result for coronary artery disease involves a clinical report coupled with a virtual meeting with a genetic counselor.

Intervention Type: GENETIC

Eligibility Criteria

Inclusion Criteria

• Males and females between 40 and 75 years of age capable and willing to provide informed consent
• Participant has high CAD PRS as defined on a clinical test

Exclusion Criteria

• Participant with a history of cardiovascular disease, defined by a diagnosis of coronary artery disease, peripheral artery disease, or cerebrovascular disease
• Participant with quantifiable plaque on a coronary computed tomography angiography
• Participant with a history of Liver disease (cirrhosis, active hepatitis, or severe hepatic disease) or any of the following recent lab results and determined to be non-transient: alanine aminotransferase greater than 3 times the upper limit of normal or total bilirubin greater than 2 times the upper limit of normal (unless due to Gilbert syndrome)
• Participant with estimated glomerular filtration rate <60 mL/min/1.73 m2 or creatinine greater than 2 times the upper limit of normal
• Patient with history of an allergic reaction or significant sensitivity to iodinated contrast, colchicine, or statins
• Patient currently taking LDL cholesterol lowering or anti- inflammatory medications including colchicine
• Participants requiring regular drugs known to be potent CY2P inhibitors (eg. ketoconazole, clarithromycin)
• Female patient who is pregnant, or breast-feeding or is considering becoming pregnant during the study
• Participant with BMI ≥ 40 kg/m2
• Participant unable to provide informed consent
• Participant unable 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 Abou-Karam, MD

Role: CONTACT

proact@mgb.org

(617)-643-4842

Facility Contacts

Role: primary

afahed@mgh.harvard.edu

Other Identifiers

2023P000935

Identifier Type: -

Identifier Source: org_study_id