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

NCT05850091 | Recruiting Phase 4 FDA Drug

• 1 other identifier: 2023P000945
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

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.

Conditions

Coronary Artery Disease

Keywords

Polygenic risk; Atherosclerosis; Genetics; Genomic medicine; Polygenic score; Precision medicine; Preventive cardiology; Coronary plaque; Inflammation; Cholesterol; Lipids; Colchicine; Statin

Outcome Measures

Primary Outcomes (1)

• Change in total non-calcified plaque volume from baseline to one 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.

  1 year

Secondary Outcomes (9)

• Change in total plaque volumes from baseline to one year

  1 year

• Change in maximal luminal stenosis from baseline to one year

  1 year

• Change in calcium score from baseline to one year

  1 year

• Change in number of high-risk features from baseline to one year

  1 year

• Change in fat attenuation index from baseline to one year

  1 year

Study Arms (4)

Group A

PLACEBO COMPARATOR

Participants will receive placebo daily

Drug: Placebo

Group B

ACTIVE COMPARATOR

Participants will receive rosuvastatin 20mg daily and placebo daily

Drug: Rosuvastatin; Drug: Placebo

Group C

ACTIVE COMPARATOR

Participants will receive colchicine 0.6mg daily and placebo daily

Drug: Colchicine; Drug: Placebo

Group D

ACTIVE COMPARATOR

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

Drug: Rosuvastatin; Drug: Colchicine

Interventions

Placebo DRUG

Capsule with sugar pill that mimics active study drugs

Group A; Group B; Group C

Rosuvastatin DRUG

Pharmacotherapy for reduction in LDL cholesterol level

Group B; Group D

Colchicine DRUG

Pharmacotherapy for inflammation inhibition

Group C; Group D

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Related Publications (1)

• Abou-Karam R, Kim MS, Jemma Cho SM, Bitar F, Gady S, Cheng F, Thompson AG, Karlson EW, Natarajan P, Ellinor PT, Foldyna B, Ghebremichael MS, Atlas SJ, Ridker PM, Lu MT, Fahed AC. Polygenic Risk Based Detection and Treatment of Subclinical Coronary Atherosclerosis in the PROACT Clinical Trials. J Am Coll Cardiol. 2026 Feb 6:S0735-1097(25)10563-9. doi: 10.1016/j.jacc.2025.12.032. Online ahead of print.

  PMID: 41706060 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease; Atherosclerosis; Inflammation

Interventions

Rosuvastatin Calcium; Colchicine

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Alkaloids

Central Study Contacts

Roukoz Abou-Karam, MD

CONTACT

(617)-643-4842; proact@mgb.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Interventional Cardiologist

Study Record Dates

• First Submitted: April 6, 2023
• First Posted: May 9, 2023
• Study Start: December 7, 2023
• Primary Completion (Estimated): May 15, 2026
• Study Completion (Estimated): May 1, 2027
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

US (1)