Clinical trial NCT06342609: Effect of Colchicine on Progression of Known Coronary Atherosclerosis in Patients With Stable Coronary Artery Disease
Official title: Effect of Colchicine on Progression of Known Coronary Atherosclerosis in Patients With STable CoROnary Artery Disease CoMpared to Placebo - EKSTROM Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Artery Disease
Lead sponsor: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Sponsor class: OTHER
First posted: 2024-04-02
Enrollment: 84
Sex: ALL
Minimum age (years): 30
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double blind Placebo controlled
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: This is a randomized double-blind, placebo-controlled, investigator-initiated trial that compares Colchicine 0.5mg/day with placebo, among patients with stable CAD. Subjects will be educated to maintain medication compliance with other prescribed medications.

Detailed description: The goal of this study is to evaluate whether treatment with Colchicine results in greater change of low attenuation plaque volume from baseline level when compared to placebo in subjects with stable Coronary Artery Disease (CAD). The Primary objective of the study is to determine progression rates of low attenuation plaque under influence of Colchicine as compared to placebo. The study will also look to determine effects of Colchicine on the morphology and composition non -calcified coronary plaque, progression of total plaque volume, progression of high vulnerability features of plaque and to assess whether these effects are modulated by a change in HsCRP and other markers of inflammation (HsCRP, IL-6, IL-1α, IL-1β, IL-18) as well as the effect on Pericoronary adipose tissue (PCAT) and Epicardial adipose tissue (EAT) volume and well as on the endothelial function.

Eligibility criteria: Inclusion Criteria:

1. Age 30-85 years
2. Proven coronary artery disease; as evidenced by coronary angiography, CT coronary angiography or a Coronary Artery Calcium Score (Agatston score \>400).
3. Clinically stable for at least six months
4. Patients should have no major competing co-morbidities or contra-indication to colchicine therapy
5. Patients must be considered to be compliant with their usual therapy
6. Willingness to be on birth control for women of childbearing age or established postmenopausal for at least 1 year
7. Patients must provide written informed consent after the scope and nature of the investigation has been explained to them.
8. Patients must be considered to be compliant with their usual therapy
9. Patients must provide written informed consent after the scope and nature of the investigation has been explained to them.
10. Patients must be able and willing to comply with the requirements of this study protocol

Exclusion Criteria:

1. Women who are pregnant, breast feeding or may be considering pregnancy during the study period
2. Renal impairment as evidenced by a serum creatinine \>150 μmol/l or estimated glomerular filtration rate (eGFR) \<50mL/min/1.73m2
3. Severe heart failure - systolic or diastolic New York Heart Association Functional classification 3 or 4
4. Moderate or severe valvular heart disease considered likely to require intervention
5. Dependency, frailty or a predicted life expectancy \< 5 years
6. Peripheral neuritis, myositis or marked myo-sensitivity to statins
7. Requirement for long term colchicine therapy for any other reason
8. Current enrollment in another trial
9. Patients with inflammatory bowel disease (Crohn's disease or ulcerative colitis) or patients with chronic diarrhea
10. Any unstable medical, psychiatric or substance abuse disorder that in the opinion of the investigator or principal investigator is likely to affect the subject's ability to complete the study or precludes the subject's participation in the study
11. Patient with progressive neuromuscular disease of Creatine Phosphokinase (CPK) level \>3 times the upper limit of normal as measured within the past 30 days and determined to be non-transient through repeat testing.
12. Patients already taking long term colchicine therapy for any other reason
13. History of malignancy within the last 5 years (other than skin cancer) or evidence of active cancer which would require concomitant cancer chemotherapy
14. Hematological or biochemical values at screening outside the reference ranges considered as clinically significant in the opinion of the investigator or PI.
15. Allergy to contrast material

Primary outcomes:
measure: Rate of change in low attenuation plaque volume as measured by multidetector computed tomography (MDCT) angiography
timeFrame: 12 months
Secondary outcomes:
measure: Effect of Colchicine on markers of inflammation using laboratory tests
timeFrame: 12 months
measure: Effects of Colchicine on Pericoronary Adipose Tissue (PCAT) volume using CTA
timeFrame: 12 months
measure: Effects of Colchicine on Epicardial Adipose Tissue (EAT) volume using CTA
timeFrame: 12 months
measure: Effect of Colchicine on the markers of Endothelial Function using Flow-mediated dilation (FMD)
timeFrame: 12 months
Other outcomes:
Locations:
city: Torrance
country: United States
facility: Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center
state: California
Study officials:
affiliation: The Lundquist Institute
name: Matthew Budoff, MD
role: PRINCIPAL_INVESTIGATOR
References: