Colchicine for Cardiovascular Disease in Diabetes

(CADENCE Trial)

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Kevin Boczar, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Ottawa Heart Institute Research Corporation

Must not be taking: Prednisone, Methotrexate, Cyclosporine, others

Disqualifiers: Severe LV dysfunction, Active infection, Cancer, others

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial tests colchicine to see if it can reduce inflammation in blood vessel plaques in high-risk patients with diabetes or pre-diabetes who recently had a heart attack or stroke. The goal is to prevent future cardiovascular events by reducing plaque inflammation. Colchicine is an ancient drug with anti-inflammatory effects, historically used for conditions like gout and familial Mediterranean fever, and has shown promise in reducing cardiovascular events by targeting inflammation in blood vessel plaques.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using certain strong inhibitors like cyclosporine or clarithromycin. It's best to discuss your current medications with the trial team.

What evidence supports the effectiveness of the drug colchicine for cardiovascular disease in diabetes?

Research shows that colchicine can reduce the risk of major heart-related problems in people with chronic coronary artery disease and diabetes, as well as in those with type 1 diabetes, by targeting inflammation, which is a key factor in heart disease. ^{1 2 3 4 5}

How is the drug colchicine unique for treating cardiovascular disease in diabetes?

Colchicine is unique because it targets inflammation, which is a key driver of cardiovascular disease in diabetes, and has been shown to reduce the risk of major cardiovascular events by 25% in patients with atherosclerotic cardiovascular disease. This anti-inflammatory approach is different from standard treatments that focus on controlling blood sugar, blood pressure, and cholesterol. ^{1 4 6 7 8}

Research Team

Kevin Boczar, MD

Principal Investigator

Ottawa Heart Institute Research Corporation

Eligibility Criteria

This trial is for adults over 18 with Type 2 Diabetes or pre-diabetes who've recently had a cardiovascular event like a heart attack or stroke. They must have stable symptoms and not be severely ill from other conditions. Pregnant women, those with severe liver, heart, or kidney issues, active infections, immune compromise, certain cancers within the last 3 years are excluded.

Inclusion Criteria

I am 18 years old or older.

Patients who have given informed consent

I recently had a heart attack or stroke related to atherosclerosis.

Exclusion Criteria

I need treatment for a serious heart valve problem.

I have severe liver issues or my ALT levels are more than three times the normal limit.

Pregnant women or breastfeeding women

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Baseline FDG PET-CT imaging and blood sampling for inflammation biomarkers

1 week

1 visit (in-person)

Treatment

Participants receive colchicine 0.6 mg daily or placebo for 6 months

6 months

3 visits (in-person) at 0, 3, and 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Colchicine (Anti-inflammatory)

Trial Overview The study tests if Colchicine can reduce inflammation in blood vessel plaques in high-risk patients using FDG PET imaging. Participants will either receive Colchicine or a placebo to see if there's an effect on plaque inflammation which contributes to cardiovascular events.

Participant Groups

Group I: Colchicine Experimental Treatment 1 Intervention

Colchicine: 0.6 mg colchicine capsule to be taken once a day.

Group II: Placebo Placebo Group 1 Intervention

Placebo: Sugar pill manufactured to mimic colchicine 0.6 mg capsule. Placebo to be taken once a day.

Who Is Running the Clinical Trial?

Ottawa Heart Institute Research Corporation

Lead Sponsor

Trials

200

Recruited

95,800+

Dr. Thierry Mesana

Ottawa Heart Institute Research Corporation

Chief Medical Officer since 2014

MD from McGill University

Dr. Rob Beanlands

Ottawa Heart Institute Research Corporation

Chief Executive Officer since 2024

MD from the University of Ottawa

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Dr. Paul C. Hébert

Canadian Institutes of Health Research (CIHR)

Chief Executive Officer

MD, University of Ottawa

Dr. Paul C. Hébert

Canadian Institutes of Health Research (CIHR)

Chief Medical Officer

MD, University of Ottawa

Findings from Research

Type 1 diabetes significantly reduces life expectancy by over 10 years, with residual cardiovascular risk contributing to high rates of heart-related events despite standard care.

Colchicine, an inexpensive anti-inflammatory drug, has been shown to reduce the risk of major cardiovascular events by 25%, suggesting it could be an effective treatment for lowering cardiovascular risk in individuals with type 1 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential of colchicine for lowering the risk of cardiovascular events in type 1 diabetes. Johansen, NJ., Knop, FK.[2023]

In the LoDoCo2 trial involving 5,522 patients with chronic coronary artery disease, colchicine significantly reduced cardiovascular events in patients without diabetes, showing a hazard ratio of 0.64, while the effect in patients with diabetes was less pronounced (HR 0.87).

Colchicine was associated with a lower incidence of new-onset type 2 diabetes mellitus (1.5% in the colchicine group vs. 2.2% in the placebo group), although this difference was not statistically significant, indicating the need for further research on its potential protective effects against diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colchicine and diabetes in patients with chronic coronary artery disease: insights from the LoDoCo2 randomized controlled trial. Mohammadnia, N., Los, J., Opstal, TSJ., et al.[2023]

Macrovascular complications from diabetes, such as large-vessel atherosclerosis, are a major cause of health issues and costs, but there is no strong evidence that glycemic control directly reduces these risks, unlike with microvascular complications.

While insulin treatment is generally favored for managing diabetes, there is concern that it may contribute to cardiovascular risks; therefore, alternative oral medications like metformin, which do not increase insulin levels, might be beneficial for some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of glycemic control on the incidence of macrovascular complications of type 2 diabetes. Stern, MP.[2019]

Diabetic patients are at a higher risk for cardiovascular disorders and experience faster degeneration of bioprosthetic aortic valves compared to non-diabetic individuals, highlighting the need for targeted interventions.

Current research is focusing on understanding the mechanisms of calcific aortic valve disease (CAVD) in diabetes, identifying potential biomarkers for diagnosis, and exploring innovative therapies such as targeted nanotherapies and tissue engineering.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aortic valve disease in diabetes: Molecular mechanisms and novel therapies. Manduteanu, I., Simionescu, D., Simionescu, A., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

The potential of colchicine for lowering the risk of cardiovascular events in type 1 diabetes. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Clinical trial evidence for cardiovascular risk reduction in type 2 diabetes. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Cardiovascular disease in type 2 diabetes mellitus: current management guidelines. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Colchicine and diabetes in patients with chronic coronary artery disease: insights from the LoDoCo2 randomized controlled trial. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

The effect of glycemic control on the incidence of macrovascular complications of type 2 diabetes. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Type-2 diabetes mellitus and cardiovascular disease. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Increased Calcific Aortic Valve Disease in response to a diabetogenic, procalcific diet in the LDLr-/-ApoB100/100 mouse model. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Aortic valve disease in diabetes: Molecular mechanisms and novel therapies. [2022]