Colchicine for Cardiovascular Disease in Diabetes
(CADENCE Trial)
Recruiting in Palo Alto (17 mi)
+1 other location
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?
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.14678
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.
See 2 more
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
See 17 more
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 OverviewThe 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
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.
Colchicine is already approved in United States for the following indications:
🇺🇸 Approved in United States as Colcrys for:
- Gout
- Familial Mediterranean Fever
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Mazankowski Alberta Heart InstituteEdmonton, Canada
University of Ottawa Heart InstituteOttawa, Canada
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Who Is Running the Clinical Trial?
Ottawa Heart Institute Research CorporationLead Sponsor
Canadian Institutes of Health Research (CIHR)Collaborator
References
The potential of colchicine for lowering the risk of cardiovascular events in type 1 diabetes. [2023]In type 1 diabetes, average life expectancy is reduced by ˃10 years as compared with outside of diabetes. Residual cardiovascular risk defines high cardiovascular event rate despite modern, guideline-recommended standard of care of established risk factors like hypertension, dyslipidaemia, and glycaemic control, and it adds importantly to these lost years of life in type 1 diabetes due to atherosclerotic cardiovascular diseases like myocardial infarction and ischaemic stroke. With a growing understanding of inflammation as an important driver of atherosclerotic cardiovascular disease, residual inflammatory risk is a novel and common risk factor and a promising target for lowering residual cardiovascular risk in type 1 diabetes. Interestingly, the inexpensive anti-inflammatory agent colchicine reduced the risk of major adverse cardiovascular events by 25% in cardiovascular outcome trials in the secondary prevention of atherosclerotic cardiovascular disease. Here, we summarize the role of inflammation as a driver of atherosclerosis and review current evidence linking inflammation and atherosclerotic cardiovascular disease in type 1 diabetes. Also, we provide an overview of the evidence base for targeting residual inflammatory risk with colchicine for lowering residual cardiovascular risk in type 1 diabetes.
Clinical trial evidence for cardiovascular risk reduction in type 2 diabetes. [2019]Major clinical trials have shown that excellent glycemic control, sustained over time, can prevent or delay the microvascular complications of diabetes, including retinopathy, nephropathy, and neuropathy. No prospective trial has clearly shown that glycemic intervention can prevent the macrovascular complications of diabetes, such as myocardial infarction, cerebrovascular accident, and amputation. However, a number of landmark clinical trials have shown the efficacy of control of blood pressure and lipids and use of antiplatelet agents (mainly aspirin) in protecting the macrovasculature of individuals with diabetes. In this article, glycemic, blood pressure, lipid, and antiplatelet trials relevant to the treatment of people with type 2 diabetes are reviewed.
Cardiovascular disease in type 2 diabetes mellitus: current management guidelines. [2019]Cardiovascular disease is the most prevalent and detrimental complication of diabetes mellitus. The incidence of cardiovascular mortality in diabetic subjects without a clinical history of previous cardiac events is as high as the incidence in nondiabetic subjects with a history of myocardial infarction. This inordinate increase in the risk of coronary events in diabetic patients is attributed to multiple factors, including glycation and oxidation of proteins and increased prevalence of classic risk factors of coronary disease, such as hypertension, obesity, and dyslipidemia. Despite advances in the management of cardiovascular disease, a large proportion of diabetic subjects continue to have uncontrolled hyperglycemia, hypertension, and dyslipidemia. In addition, certain medical interventions with established efficacy in the general population do not appear to be appropriate for diabetic subjects. Recently published clinical trials of managing coronary risk factors indicate that more stringent goals of therapy should be set for diabetic patients. In this communication, some of these landmark studies are reviewed and some practical guidelines of management are suggested.
Colchicine and diabetes in patients with chronic coronary artery disease: insights from the LoDoCo2 randomized controlled trial. [2023]Despite optimal treatment, patients with chronic coronary artery disease (CAD) and diabetes mellitus (DM) are at high risk of cardiovascular events, emphasizing the need for new treatment options. The Low-Dose Colchicine 2 (LoDoCo2) trial demonstrated that colchicine reduces cardiovascular risk in patients with chronic CAD. This analysis determines the efficacy of colchicine in patients with chronic CAD and DM as well as the effect of colchicine on the development of new-onset type 2 diabetes mellitus (T2DM).
The effect of glycemic control on the incidence of macrovascular complications of type 2 diabetes. [2019]Of all the complications of diabetes mellitus, macrovascular complications, ie, large-vessel atherosclerosis, account for the largest share of morbidity, mortality, and health care expenditures. Whereas there is now highly persuasive evidence that glycemic control reduces the risk of microvascular complications in type 1 diabetes, and probably in type 2 diabetes as well, such evidence is unavailable for macrovascular complications. Prospective epidemiologic studies, however, indicate that poor glycemic control enhances cardiovascular risk, and a number of biochemical mechanisms have been advanced to explain this phenomenon. However, data from animal studies, in vitro studies, and prospective epidemiologic studies suggest that endogenous insulin or insulin resistance may be atherogenic. Thus, a dilemma exists for insulin treatment, although the weight of evidence still favors its aggressive use. For persons whose glycemia can be adequately controlled with oral agents, the use of agents such as metformin and troglitazone--which do not raise, and may even lower, insulin concentrations--may offer an advantage. Definitive clinical trials on the benefits and risks of insulin therapy related to macrovascular complications are lacking and urgently needed.
Type-2 diabetes mellitus and cardiovascular disease. [2019]The global prevalence of diabetes has risen in adults from 4.7% in 1980 to 8.5% in 2014. 90-95% of adults with diabetes have Type 2 diabetes (T2D). This paper focuses on the diagnosis and treatment of T2D patients who have or are at risk for cardiovascular disease. Hyperglycemia, insulin resistance and excess fatty acids increase oxidative stress, disrupt protein kinase C signaling and increase advanced glycation end-products that result in vascular inflammation, vasoconstriction, thrombosis and atherogenesis. Intensive T2D treatment produces a ≥10% risk reduction in major macrovascular and microvascular events. Glucose-lowering therapies must be individualized. Metformin is an optimal drug for monotherapy. If hemoglobin A1c is not at goal, a sodium-glucose cotransporter-2 inhibitor or a dipeptidyl peptidase-4 inhibitor should be considered for therapy with metformin. Coronary angioplasty/stenting is recommended for diabetic patients with acute myocardial infarctions. Coronary artery bypass grafting is recommended for symptomatic diabetic patients with multivessel disease.
Increased Calcific Aortic Valve Disease in response to a diabetogenic, procalcific diet in the LDLr-/-ApoB100/100 mouse model. [2020]Label="OBJECTIVE" NlmCategory="OBJECTIVE">Calcific aortic valve disease (CAVD) is a major cause of aortic stenosis (AS) and cardiac insufficiency. Patients with type II diabetes mellitus (T2DM) are at heightened risk for CAVD, and their valves have greater calcification than nondiabetic valves. No drugs to prevent or treat CAVD exist, and animal models that might help identify therapeutic targets are sorely lacking. To develop an animal model mimicking the structural and functional features of CAVD in people with T2DM, we tested a diabetogenic, procalcific diet and its effect on the incidence and severity of CAVD and AS in the, LDLr-/-ApoB100/100 mouse model.
Aortic valve disease in diabetes: Molecular mechanisms and novel therapies. [2022]Valve disease and particularly calcific aortic valve disease (CAVD) and diabetes (DM) are progressive diseases constituting a global health burden for all aging societies (Progress in Cardiovascular Diseases. 2014;56(6):565: Circulation Research. 2021;128(9):1344). Compared to non-diabetic individuals (The Lancet. 2008;371(9626):1800: The American Journal of Cardiology. 1983;51(3):403: Journal of the American College of Cardiology. 2017;69(12):1523), the diabetic patients have a significantly greater propensity for cardiovascular disorders and faster degeneration of implanted bioprosthetic aortic valves. Previously, using an original experimental model, the diabetic-hyperlipemic hamsters, we have shown that the earliest alterations induced by these conditions occur at the level of the aortic valves and, with time these changes lead to calcifications and CAVD. However, there are no pharmacological treatments available to reverse or retard the progression of aortic valve disease in diabetes, despite the significant advances in the field. Therefore, it is critical to uncover the mechanisms of valve disease progression, find biomarkers for diagnosis and new targets for therapies. This review aims at presenting an update on the basic research in CAVD in the context of diabetes. We provide an insight into the accumulated data including our results on diabetes-induced progressive cell and molecular alterations in the aortic valve, new potential biomarkers to assess the evolution and therapy of the disease, advancement in targeted nanotherapies, tissue engineering and the potential use of circulating endothelial progenitor cells in CAVD.