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

NCT ID: NCT05850091

Last Updated: 2025-07-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-12-07

Study Completion Date

2027-02-01

Brief Summary

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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

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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.

Conditions

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Coronary Artery Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Group A

Participants will receive placebo daily

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Capsule with sugar pill that mimics active study drugs

Group B

Participants will receive rosuvastatin 20mg daily and placebo daily

Group Type ACTIVE_COMPARATOR

Rosuvastatin

Intervention Type DRUG

Pharmacotherapy for reduction in LDL cholesterol level

Placebo

Intervention Type DRUG

Capsule with sugar pill that mimics active study drugs

Group C

Participants will receive colchicine 0.6mg daily and placebo daily

Group Type ACTIVE_COMPARATOR

Colchicine

Intervention Type DRUG

Pharmacotherapy for inflammation inhibition

Placebo

Intervention Type DRUG

Capsule with sugar pill that mimics active study drugs

Group D

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

Group Type ACTIVE_COMPARATOR

Rosuvastatin

Intervention Type DRUG

Pharmacotherapy for reduction in LDL cholesterol level

Colchicine

Intervention Type DRUG

Pharmacotherapy for inflammation inhibition

Interventions

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Rosuvastatin

Pharmacotherapy for reduction in LDL cholesterol level

Intervention Type DRUG

Colchicine

Pharmacotherapy for inflammation inhibition

Intervention Type DRUG

Placebo

Capsule with sugar pill that mimics active study drugs

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

40 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Massachusetts General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Akl C. Fahed, MD, MPH

Interventional Cardiologist

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Roukoz Abou-Karam, MD

Role: CONTACT

(617)-643-4842

Facility Contacts

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Role: primary

Other Identifiers

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2023P000945

Identifier Type: -

Identifier Source: org_study_id

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