PROACT 2: Polygenic Risk-based Detection of Subclinical Coronary Atherosclerosis and Intervention With Statin and Colchicine

Sponsor

Massachusetts General Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05850091

Collaborator

National Heart, Lung, and Blood Institute (NHLBI) (NIH)

150

Enrollment

Location

Arms

Anticipated Duration (Months)

3.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of this double-blind randomized controlled trial is to determine if combination therapy of statin and low-dose colchicine - compared with statin alone - favorably modulates progression and composition of subclinical coronary atherosclerosis in individuals with high polygenic risk for coronary artery disease.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease	Drug: Rosuvastatin Drug: Colchicine	Phase 4

Detailed Description

The main question PROACT 2 aims to answer is whether and how 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 150 individuals with high polygenic risk for coronary artery disease and subclinical plaque on coronary computed tomography angiography. Participants will be randomized in a 1:1 allocation to rosuvastatin 20mg and colchicine 0.6mg daily vs. rosuvastatin 20mg and placebo. 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Polygenic Risk-based Detection of Subclinical Coronary Atherosclerosis and Intervention With Statin and Colchicine

Anticipated Study Start Date :

Jul 1, 2023

Anticipated Primary Completion Date :

Jul 1, 2026

Anticipated Study Completion Date :

Jul 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Intervention Participants will receive rosuvastatin 20mg daily and colchicine 0.6mg daily	Drug: Rosuvastatin Pharmacotherapy for reduction in cholesterol level Drug: Colchicine Pharmacotherapy for inflammation inhibition
Placebo Comparator: Control Participants will receive rosuvastatin 20mg daily and placebo	Drug: Rosuvastatin Pharmacotherapy for reduction in cholesterol level

Arm

Intervention/Treatment

Active Comparator: Intervention

Participants will receive rosuvastatin 20mg daily and colchicine 0.6mg daily

Drug: Rosuvastatin

Pharmacotherapy for reduction in cholesterol level

Drug: Colchicine

Pharmacotherapy for inflammation inhibition

Placebo Comparator: Control

Participants will receive rosuvastatin 20mg daily and placebo

Drug: Rosuvastatin

Pharmacotherapy for reduction in cholesterol level

Outcome Measures

Primary Outcome Measures

Change in total non-calcified plaque volume from baseline to one year [1 year]
The primary outcome of this study is the change in total non-calcified plaque volume between the two groups from baseline to one year. This outcome will be measured using coronary computed tomography angiography (CCTA) and reported in cubic millimeters (mm³). The comparison of the changes in non-calcified plaque volume will help assess the effectiveness of the intervention on plaque progression and composition.

Secondary Outcome Measures

Change in total plaque volumes from baseline to one year [1 year]
The change in the following plaque volumes will be compared between the two groups from baseline to one year: total plaque volume, total calcified plaque volume, and total low attenuation plaque volume. These volumes will be analyzed individually and reported in cubic millimeters (mm³).
Change in maximal luminal stenosis from baseline to one year [1 year]
The change in maximal luminal stenosis will be compared between the two groups from baseline to one year, reported as a percentage (%).
Change in calcium score from baseline to one year [1 year]
The change in calcium score will be compared between the two groups from baseline to one year, reported in Agatston units.
Change in number of high-risk features from baseline to one year [1 year]
The change in the number of high-risk features will be compared between the two groups from baseline to one year, reported as a count (number of features).
Change in fat attenuation index from baseline to one year [1 year]
The change in fat attenuation index will be compared between the two groups from baseline to one year, reported in Hounsfield units (HU).
Change in low-density lipoprotein cholesterol (LDL-C) from baseline to one year [1 year]
The change in low-density lipoprotein cholesterol (LDL-C) will be compared between the two groups from baseline to one year, reported in milligrams per deciliter (mg/dL).
Change in C-reactive protein (CRP) from baseline to one year [1 year]
The change in C-reactive protein (CRP) will be compared between the two groups from baseline to one year, reported in milligrams per liter (mg/L).
Change in Interleukin-6 and Interleukin-1 beta (IL-1ß) from baseline to one year [1 year]
The change in Interleukin-6 (IL-6) and Interleukin-1 beta (IL-1ß) will be compared between the two groups from baseline to one year. Both biomarkers will be analyzed individually and reported in picograms per milliliter (pg/mL).

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

High polygenic risk for coronary artery disease
Subclinical atherosclerosis defined as plaque visible on coronary computed tomography angiography and causing <70% luminal stenosis

Exclusion Criteria:

Cardiovascular disease, defined by a diagnosis of coronary artery disease, peripheral artery disease, or cerebrovascular disease
Contraindication to taking colchicine or rosuvastatin (allergy, liver or kidney disease)
Taking LDL cholesterol lowering or anti- inflammatory medications
Contraindications to coronary computed tomography angiography (chronic kidney disease, contrast allergy)
Pregnancy or breastfeeding
Inability to provide informed consent
Estimated glomerular filtration rate <60 mL/min/1.73 m2
Allergy to iodinated contrast
BMI ≥ 40 kg/m2
Inability to hold breath for 10 seconds.