What side effects are associated with this type of intervention?

Colchicine, an anti-inflammatory drug being studied for its effects on plaque inflammation in atherosclerosis, can cause gastrointestinal side effects such as diarrhea, nausea, and abdominal pain. Statins, another common treatment, may lead to muscle pain, liver enzyme abnormalities, and, rarely, rhabdomyolysis. PCSK9 inhibitors, used to lower LDL cholesterol, can cause injection site reactions, hypersensitivity reactions, and, in rare cases, neurocognitive symptoms. Antiplatelet agents like aspirin can increase the risk of gastrointestinal bleeding and, in some cases, cause allergic reactions.

What prior FDA approvals exist?

FDA-approved treatments for atherosclerosis that focus on anti-inflammatory actions include statins such as atorvastatin and rosuvastatin, which lower cholesterol and reduce arterial inflammation. PCSK9 inhibitors like alirocumab and evolocumab also lower LDL cholesterol and exhibit anti-inflammatory properties. These drugs aim to mitigate cardiovascular risks by addressing both lipid accumulation and inflammation in atherosclerotic plaques.

What other types of research exist?

Promising novel alternatives to colchicine for treating plaque inflammation in atherosclerosis patients include: 1) PCSK9 inhibitors (e.g., alirocumab, evolocumab) which have shown anti-inflammatory effects in addition to lipid-lowering properties; 2) IL-1β inhibitors (e.g., canakinumab) which target inflammatory pathways directly involved in atherosclerosis; 3) IL-6 inhibitors (e.g., tocilizumab) which have demonstrated potential in reducing vascular inflammation. These alternatives are being investigated for their efficacy in reducing plaque inflammation and improving cardiovascular outcomes.

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Anti-inflammatory

Colchicine for Cardiovascular Disease in Diabetes (CADENCE Trial)

Phase 3

Recruiting

Led By Rob S Beanlands, MD

Research Sponsored by Ottawa Heart Institute Research Corporation

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients aged ≥18 years

Patients with Type 2 Diabetes (on diet, oral hypo-glycemic agents and/or insulin) or pre-diabetes

Must not have

Patients with severe valve disease requiring intervention

Patients with a history of cirrhosis, chronic active hepatitis or severe hepatic disease or with alanine aminotransferase (ALT) levels greater than 3 times the upper limit of normal

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 6 months

Awards & highlights

Pivotal Trial

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Colchicine may cause side effects such as digestive upset (like diarrhea), blood disorders (low counts of white cells and platelets), muscle pain/weakness, and possibly increased risk of infection due to its impact on the body's inflammatory response.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 18 years old or older.

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

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I need treatment for a serious heart valve problem.

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

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I am not willing to use two forms of birth control during the study.

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I have chronic diarrhea.

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My heart failure is severe and not well-controlled.

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I have an active inflammatory condition or am on systemic anti-inflammatory therapy.

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I am allergic to dyes or my kidney function is low, so I will have a PET/CT instead of a CTA.

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My kidney function is reduced with a GFR less than 50.

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I am currently taking strong medication that affects how drugs are processed in my body.

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My heart's pumping ability is severely reduced.

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I have atrial fibrillation and have had a stroke or TIA.

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I currently have an active infection and am taking antibiotics.

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I often get infections due to a weak immune system.

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I am unable to understand and give consent for treatment.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 6 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~6 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 6 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

6 month change in FDG uptake TBR (Tissue to Blood Ratio) in the MDS (Maximum Disease Segment)

Secondary study objectives

6 month change in FDG uptake SUV (standard uptake value) in the MDS of each vascular region: aorta, left and right carotid.

Aorta

Levels of Interleukin-6 (IL-6) (pg/ml) and its change.

+1 more

Other study objectives

Exploratory outcomes - Levels of activated monocytes

Exploratory outcomes - MACE

Exploratory outcomes - Plasma levels of cytokines (pg/ml)

+4 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: ColchicineExperimental Treatment1 Intervention

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

Group II: PlaceboPlacebo Group1 Intervention

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

0 / 16Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for atherosclerosis include statins, antiplatelet agents, and anti-inflammatory drugs like colchicine. Statins work by lowering LDL cholesterol levels and stabilizing plaque, reducing the risk of plaque rupture. Antiplatelet agents, such as aspirin, prevent blood clots from forming on plaques, thereby reducing the risk of heart attacks and strokes. Colchicine, an anti-inflammatory drug, targets plaque inflammation, which is a key factor in plaque instability and rupture. This anti-inflammatory action is crucial for atherosclerosis patients as it helps to reduce the risk of acute cardiovascular events by stabilizing the plaques and preventing their rupture.