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

Coronary Artery Disease Clinical Trial

— PROACT 1  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05819814
• Other study ID #: 2023P000935
• Status: Recruiting
• Phase: N/A
• Start date: December 7, 2023
• Est. completion date: July 2027

Study information

• Verified date: May 2024
• Source: Massachusetts General Hospital
• Contact: Fangzhou Cheng
• Phone: (617)-643-4842
• Email: proact[@]mgb.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: July 2027
• Est. primary completion date: July 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Atherosclerosis
• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Genetic:
• 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.

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assess the impact of disclosing a high polygenic risk result for coronary artery disease on change in cardiovascular health	Change in cardiovascular health from baseline to one year as measured by the American Heart Association's Life's Essential 8 (LE8) Score will be compared between an intervention arm that receives a high polygenic risk result for coronary artery disease and a control group that receives standard of care. The LE8 score ranges between 0 and 100 with higher numbers indicating better cardiovascular health.	1 year