Clinical trial NCT05850091: Polygenic Risk-based Detection of Subclinical Coronary Atherosclerosis and Intervention With Statin and Colchicine
Official title: Polygenic Risk-based Detection of Subclinical Coronary Atherosclerosis and Intervention With Statin and Colchicine
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Coronary Artery Disease
Keywords: Polygenic risk
Atherosclerosis
Genetics
Genomic medicine
Polygenic score
Precision medicine
Preventive cardiology
Coronary plaque
Inflammation
Cholesterol
Lipids
Colchicine
Statin
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2023-05-09
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: TREATMENT

Brief summary: 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.

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.

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
* 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

Primary outcomes:
measure: Change in total non-calcified plaque volume from baseline to one year
timeFrame: 1 year
Secondary outcomes:
measure: Change in total plaque volumes from baseline to one year
timeFrame: 1 year
measure: Change in maximal luminal stenosis from baseline to one year
timeFrame: 1 year
measure: Change in calcium score from baseline to one year
timeFrame: 1 year
measure: Change in number of high-risk features from baseline to one year
timeFrame: 1 year
measure: Change in fat attenuation index from baseline to one year
timeFrame: 1 year
measure: Progression in non-calcified plaque volume from baseline to one year
timeFrame: 1 year
measure: Change in low-density lipoprotein cholesterol (LDL-C) from baseline to one year
timeFrame: 1 year
measure: Change in C-reactive protein (CRP) from baseline to one year
timeFrame: 1 year
measure: Change in Interleukin-6 and Interleukin-1 beta (IL-1ß) from baseline to one year
timeFrame: 1 year
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
References: