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

Primary Purpose

Coronary Artery Disease

Status
Not yet recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Rosuvastatin
Colchicine
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Coronary Artery Disease focused on measuring Polygenic risk, Atherosclerosis, Genetics, Genomic medicine, Polygenic score, Precision medicine, Preventive cardiology, Coronary plaque, Inflammation, Cholesterol, Lipids, Colchicine, Statin

Eligibility Criteria

40 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Massachusetts General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Intervention

Control

Arm Description

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

Participants will receive rosuvastatin 20mg daily and placebo

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Change in total plaque volumes from baseline to one 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
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
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
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
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
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
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
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).

Full Information

First Posted
April 6, 2023
Last Updated
April 28, 2023
Sponsor
Massachusetts General Hospital
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT05850091
Brief Title
Polygenic Risk-based Detection of Subclinical Coronary Atherosclerosis and Intervention With Statin and Colchicine
Acronym
PROACT 2
Official Title
Polygenic Risk-based Detection of Subclinical Coronary Atherosclerosis and Intervention With Statin and Colchicine
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
July 2023 (Anticipated)
Primary Completion Date
July 2026 (Anticipated)
Study Completion Date
July 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Disease
Keywords
Polygenic risk, Atherosclerosis, Genetics, Genomic medicine, Polygenic score, Precision medicine, Preventive cardiology, Coronary plaque, Inflammation, Cholesterol, Lipids, Colchicine, Statin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intervention
Arm Type
Active Comparator
Arm Description
Participants will receive rosuvastatin 20mg daily and colchicine 0.6mg daily
Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
Participants will receive rosuvastatin 20mg daily and placebo
Intervention Type
Drug
Intervention Name(s)
Rosuvastatin
Intervention Description
Pharmacotherapy for reduction in cholesterol level
Intervention Type
Drug
Intervention Name(s)
Colchicine
Intervention Description
Pharmacotherapy for inflammation inhibition
Primary Outcome Measure Information:
Title
Change in total non-calcified plaque volume from baseline to one year
Description
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.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Change in total plaque volumes from baseline to one year
Description
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).
Time Frame
1 year
Title
Change in maximal luminal stenosis from baseline to one year
Description
The change in maximal luminal stenosis will be compared between the two groups from baseline to one year, reported as a percentage (%).
Time Frame
1 year
Title
Change in calcium score from baseline to one year
Description
The change in calcium score will be compared between the two groups from baseline to one year, reported in Agatston units.
Time Frame
1 year
Title
Change in number of high-risk features from baseline to one year
Description
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).
Time Frame
1 year
Title
Change in fat attenuation index from baseline to one year
Description
The change in fat attenuation index will be compared between the two groups from baseline to one year, reported in Hounsfield units (HU).
Time Frame
1 year
Title
Change in low-density lipoprotein cholesterol (LDL-C) from baseline to one year
Description
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).
Time Frame
1 year
Title
Change in C-reactive protein (CRP) from baseline to one year
Description
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).
Time Frame
1 year
Title
Change in Interleukin-6 and Interleukin-1 beta (IL-1ß) from baseline to one year
Description
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).
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Roukoz Abou Karam
Phone
6174121147
Email
raboukaram@mgh.harvard.edu
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Data will be tabulated and analyzed. Study site will not share any of the subject identifiers.

Learn more about this trial

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

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