Clinical trial NCT05819814: Polygenic Risk-based Detection of Subclinical Coronary Atherosclerosis and Change in Cardiovascular Health
Official title: Polygenic Risk-based Detection of Subclinical Coronary Atherosclerosis and Change in Cardiovascular Health
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Coronary Artery Disease
Keywords: Coronary artery disease
Polygenic risk score
Genetics
Genomic medicine
Precision medicine
Preventive cardiology
Risk prediction
Cardiovascular health
Coronary CT angiogram
Coronary plaque
Atherosclerosis
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2023-04-19
Enrollment: 200
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Assess the impact of disclosing a high polygenic risk result for coronary artery disease on change in cardiovascular health
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
References: