Polygenic Risk-based Detection of Subclinical Coronary Atherosclerosis and Intervention With Statin and Colchicine
Purpose
The goal of this double-blind randomized controlled trial is to determine how treatment with high intensity statin, low-dose colchicine, and their combination modulates progression and composition of coronary atherosclerosis in individuals with high polygenic risk for coronary artery disease.
Condition
- Coronary Artery Disease
Eligibility
- Eligible Ages
- Between 40 Years and 75 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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 - Participant with subclinical atherosclerosis defined as plaque visible on CCTA and causing <70% luminal stenosis
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 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
Study Design
- Phase
- Phase 4
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Placebo Comparator Group A |
Participants will receive placebo daily |
|
|
Active Comparator Group B |
Participants will receive rosuvastatin 20mg daily and placebo daily |
|
|
Active Comparator Group C |
Participants will receive colchicine 0.6mg daily and placebo daily |
|
|
Active Comparator Group D |
Participants will receive rosuvastatin 20mg daily and colchicine 0.6mg daily |
|
Recruiting Locations
More Details
- Status
- Recruiting
- Sponsor
- Massachusetts General Hospital
Detailed Description
The main question PROACT 2 aims to answer is whether and how single or dual targeting of cholesterol-lowering and inflammation modulates coronary plaque in individuals with high polygenic risk and subclinical coronary atherosclerosis. This is a double-blind randomized controlled trial of 200 individuals with high polygenic risk for coronary artery disease and subclinical plaque on coronary computed tomography angiography. Participants will be randomized into four equal treatment groups: group A receiving a placebo daily, group B receiving rosuvastatin 20mg daily, group C receiving colchicine 0.6mg daily, and group D receiving both rosuvastatin 20mg daily and colchicine 0.6mg daily. The primary outcome is change in total non-calcified plaque volume on coronary computed tomography angiography from baseline to one year. Multiple secondary plaque imaging and biomarker outcomes will be explored in this pilot mechanistic trial.