Effect of Colchicine on Progression of Known Coronary Atherosclerosis in Patients With Stable Coronary Artery Disease

Coronary Artery Disease Clinical Trial

— EKSTROM  

Official title:

Effect of Colchicine on Progression of Known Coronary Atherosclerosis in Patients With STable CoROnary Artery Disease CoMpared to Placebo - EKSTROM Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06342609
• Other study ID #: 32857-01-EKSTROM
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: March 15, 2023
• Est. completion date: September 7, 2024

Study information

• Verified date: March 2024
• Source: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 84
• Est. completion date: September 7, 2024
• Est. primary completion date: September 7, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Atherosclerosis
• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• Colchicine 0.5 MG
0.5mg per day of Colchicine orally administered

Locations

Country	Name	City	State
United States	Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of change in low attenuation plaque volume as measured by multidetector computed tomography (MDCT) angiography	Reduction of low attenuation plaque volume from baseline (start of the study) till the final visit will be measured using Coronary Computed Tomography Angiography (CTA).	12 months
Secondary	Effect of Colchicine on markers of inflammation using laboratory tests	To determine the effect of Colchicine on markers of inflammation (IL-6, IL-1a, IL-1ß, IL-18 high sensitivity C-reactive protein)	12 months
Secondary	Effects of Colchicine on Pericoronary Adipose Tissue (PCAT) volume using CTA	To determine the effects of Colchicine on PCAT volume.	12 months
Secondary	Effects of Colchicine on Epicardial Adipose Tissue (EAT) volume using CTA	To determine the effects of Colchicine on EAT volume.	12 months
Secondary	Effect of Colchicine on the markers of Endothelial Function using Flow-mediated dilation (FMD)	To determine the effect of Colchicine on Endothelial function using FMD.	12 months