Colchicine for Cardiovascular Disease in Diabetes

(CADENCE Trial)

Recruiting at 1 trial location

Overseen By Rob S Beanlands, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

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) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 6 months

115 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether colchicine, a medication, can reduce inflammation in artery plaques to help prevent heart attacks and strokes in people with diabetes or pre-diabetes. Researchers focus on individuals who have recently experienced a heart attack, stroke, or mini-stroke and are at high risk for future cardiovascular events. Participants will receive either colchicine or a placebo (an inactive pill) to compare the effects. Those with diabetes or pre-diabetes who have had a recent cardiovascular event might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that colchicine is generally safe for people, especially in low doses. Studies have found that colchicine can effectively treat heart conditions like pericarditis and atherosclerosis, with most patients tolerating it well. Recent trials suggest that its ability to reduce inflammation may help lower the risk of heart attacks and strokes.

A meta-analysis, which combines results from several studies, also supports colchicine's safety for patients with heart diseases caused by plaque build-up in arteries. In 2023, the FDA approved colchicine for long-term use to reduce the risk of heart attacks and strokes. This approval indicates a strong safety record, as the FDA requires thorough safety checks before granting approval.

Overall, colchicine appears to be a well-tolerated and safe option for people at risk of heart-related issues. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Colchicine is unique because, unlike typical treatments for cardiovascular disease in diabetes that focus on controlling blood sugar and cholesterol, it targets inflammation directly. This anti-inflammatory action is crucial because inflammation plays a significant role in cardiovascular complications for people with diabetes. Researchers are excited about colchicine because it could offer a novel way to reduce heart-related risks by addressing a different aspect of the disease, potentially improving outcomes for patients who don't respond adequately to standard therapies.

What evidence suggests that colchicine might be an effective treatment for cardiovascular disease in diabetes?

Research has shown that colchicine can help lower the risk of heart problems. Specifically, the Low-Dose Colchicine 2 (LoDoCo2) trial found that colchicine reduced heart issues in people with long-term coronary artery disease (CAD). Studies have confirmed that colchicine helps manage heart disease by reducing inflammation. Evidence also suggests that colchicine lowers the chance of major heart events, like heart attacks, in people with CAD. In this trial, participants will receive either colchicine or a placebo to evaluate its effectiveness in reducing heart-related risks in individuals with diabetes and other heart conditions. ^{1 3 4 6 7}

Who Is on the Research Team?

Kevin Boczar, MD

Principal Investigator

Ottawa Heart Institute Research Corporation

Are You a Good Fit for This Trial?

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

Patients who have given informed consent

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

I have Type 2 Diabetes or pre-diabetes and may be on medication or insulin.

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Colchicine

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.

How Is the Trial Designed?

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.

Colchicine is already approved in United States for the following indications:

Approved in United States as Colcrys for:

• Gout
• Familial Mediterranean Fever

Who Is Running the Clinical Trial?

Ottawa Heart Institute Research Corporation

Lead Sponsor

Trials

200

Recruited

95,800+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Published Research Related to This Trial

Maintaining excellent glycemic control over time can effectively prevent or delay microvascular complications of diabetes, such as retinopathy, nephropathy, and neuropathy, as shown in major clinical trials.

While no prospective trial has definitively proven that glycemic control prevents macrovascular complications like heart attacks or strokes, controlling blood pressure, managing lipid levels, and using antiplatelet agents (like aspirin) have been shown to protect against these serious complications in individuals with diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trial evidence for cardiovascular risk reduction in type 2 diabetes. Stanciu, I., Peralta, ML., Emanuele, MA., et al.[2019]

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]

A new animal model of calcific aortic valve disease (CAVD) was developed using LDLr-/-ApoB100/100 mice fed a diabetogenic, procalcific diet, which resulted in a 77% incidence of significant aortic stenosis (AS) and structural changes similar to those seen in humans with type II diabetes mellitus (T2DM).

This model demonstrated impaired cardiac function and increased calcification in aortic valve leaflets, making it a valuable tool for studying the mechanisms of CAVD and potentially developing new treatments for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased Calcific Aortic Valve Disease in response to a diabetogenic, procalcific diet in the LDLr-/-ApoB100/100 mouse model. Scatena, M., Jackson, MF., Speer, MY., et al.[2020]

The prevalence of Type 2 diabetes (T2D) has increased significantly, with intensive treatment reducing the risk of major cardiovascular events by at least 10%, highlighting the importance of managing diabetes to prevent heart-related complications.

Metformin is recommended as the first-line treatment for T2D, and if blood sugar levels are not adequately controlled, additional medications like sodium-glucose cotransporter-2 inhibitors or dipeptidyl peptidase-4 inhibitors should be considered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Type-2 diabetes mellitus and cardiovascular disease. Henning, RJ.[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]

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]

Diabetic patients face a significantly higher risk of cardiovascular events, comparable to nondiabetic individuals with a history of heart issues, due to factors like protein glycation, oxidation, and common risk factors such as hypertension and obesity.

Recent clinical trials suggest that diabetic patients should aim for more stringent management goals for coronary risk factors, as standard interventions may not be as effective for them.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

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]

Citations

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Colchicine and diabetes in patients with chronic coronary ...

The Low-Dose Colchicine 2 (LoDoCo2) trial demonstrated that colchicine reduces cardiovascular risk in patients with chronic CAD.

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Colchicine and diabetes in patients with chronic coronary ...

The Low-Dose Colchicine 2 (LoDoCo2) trial demonstrated that colchicine reduces cardiovascular risk in patients with chronic CAD.

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ahajournals.org

ahajournals.org/doi/10.1161/ATVBAHA.124.319851

Colchicine's Role in Cardiovascular Disease Management

Randomized clinical trials established low-dose colchicine as an effective treatment for pericarditis and atherosclerotic cardiovascular disease ...

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Colchicine in Patients with Chronic Coronary Disease

Evidence from a recent trial has shown that the antiinflammatory effects of colchicine reduce the risk of cardiovascular events in patients with recent ...

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academic.oup.com

academic.oup.com/eurheartj/article/46/26/2552/8123897

Long-term trials of colchicine for secondary prevention of ...

Several trials in the CAD population have shown that colchicine is effective in reducing major adverse cardiovascular events [MACE: ...

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pmc.ncbi.nlm.nih.gov/articles/PMC9512890/

A meta-analysis of randomized controlled clinical trials

Long-term low-dose colchicine treatment may significantly reduce the risk of cardiovascular events. Furthermore, colchicine significantly reduced the risk of ...

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Colchicine for Cardiovascular Disease: Navigating the Gap ...

Low-dose colchicine was approved in 2023 for chronic use by the US Food and Drug Administration to “reduce the risk of myocardial infarction, stroke, coronary ...