The purpose of this study is to evaluate the effects of Empagliflozin on cardiac structure, function and circulating biomarkers in patients with Type II diabetes. Empagliflozin (anti-hyperglycemic agent), approved by Health Canada and the FDA for the treatment of Type II diabetes, demonstrated a reduction in cardiovascular deaths and heart failure from a previous post-marketing clinical trial. The use of empagliflozin to treat patients with diabetes and heart disease has been approved by Health Canada. However, the process by which it may give this beneficial effect remains unclear and needs further investigation. Therefore, the aim of this study is to provide a fundamental understanding of the mechanistic basis by which Empagliflozin could provide its potential cardio-protective effects by employing the use of Cardiac Magnetic Resonance Imaging (CMRI).
The prevalence of heart failure in Canada is high, affecting 1-3% of total population, representing one of the health care system's most expensive diagnoses. Type 2 diabetes is a significant risk factor for heart disease, and the presence of both type 2 diabetes and heart disease increases the risk of other major health complications including death. A translational study is fundamental in understanding of the potential mechanistic basis of empagliflozin's cardiac benefit. The study drug, empagliflozin (marketed as Jardiance), belongs to a class of medications that lowers blood glucose (sugar) by preventing glucose from entering back into blood circulation and ensures it is eliminated in urine. It is approved by the FDA and Health Canada for the treatment of type 2 diabetes. This is a double-blind, randomized, placebo-controlled, parallel-group phase IV study of empagliflozin vs. placebo in patients with type 2 diabetes with inadequate glycemic control and at high cardiovascular risk. The purpose is to better understand how empagliflozin could potentially improve heart function with the use of CMRI. Patients who have given informed consent will undergo a baseline CMRI and will then be randomly assigned in a 1:1 basis to either empagliflozin 10 mg once daily (OD) or matching placebo. The aim of the study is to consent 90 eligible subjects, who will be followed for 26 weeks. An end of study CMRI will be performed at 26 weeks. The study is comprised of 6 study visits and enrolled subjects will be followed for 6 months. The patients will be assessed using CMRI, which is considered the "gold standard" for measuring left ventricular (LV) volume, mass, and ejection fraction. Patients will undergo two CMRI examinations: at baseline and 6 months after surgery. In addition, the investigators will be investigating changes from baseline in LV end-diastolic volume, end-systolic volume, LV ejection fraction, regional LV diastolic and systolic function, aortic pulse wave velocity and distensibility (as measures of arterial stiffness) via CMR imaging in patients with type 2 diabetes treated with empagliflozin compared to those who receive placebo. Also, changes from baseline on a panel of biomarkers involved in the pathophysiology of heart will be evaluated at baseline, 1 months and 6 months, in patients with type 2 diabetes treated with empagliflozin. Study assessments and potential adverse events reporting will be undertaken at each study visit.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
DIAGNOSTIC
Masking
DOUBLE
Enrollment
97
single oral tablet once daily.
single oral tablet once daily.
St. Michael's Hospital
Toronto, Ontario, Canada
Left Ventricular (LV) mass Changes
Changes in Left Ventricular (LV) mass (indexed to BSA) at 6 months in patients with Type 2 diabetes who receive empagliflozin vs. placebo. This will be measured using CMRI.
Time frame: 6 months
LV end-diastolic volume
Changes in LV end-diastolic volume (indexed to BSA) at baseline and at 6 months in patients with type 2 diabetes treated with empagliflozin. This will be measured using CMRI.
Time frame: 6 months
End-systolic volume (indexed to BSA)
Changes in end-systolic volume (indexed to BSA) at baseline and at 6 months in patients with type 2 diabetes treated with empagliflozin. This will be measured using CMRI.
Time frame: 6 months
Left Ventricular Ejection Fraction (LVEF)
Changes LVEF at baseline and at 6 months in patients with type 2 diabetes treated with empagliflozin. This will be measured using CMRI.
Time frame: 6 months
Regional LV diastolic function
Changes in Regional LV diastolic function at baseline and at 6 months in patients with type 2 diabetes treated with empagliflozin. This will be measured using CMRI.
Time frame: 6 months
Regional LV systolic function
Changes in Regional LV systolic function at baseline and at 6 months in patients with type 2 diabetes treated with empagliflozin. This will be measured using CMRI.
Time frame: 6 months
Aortic pulse wave velocity and distensibility
Changes in aortic pulse wave velocity and distensibility (as arterial stiffness) at baseline and at 6 months in patients with type 2 diabetes treated with empagliflozin.
Time frame: 6 months
Biomarkers
Changes on a panel of biomarkers involved in the pathophysiology of heart failure at baseline, 1 months and 6 months, in patients with type 2 diabetes treated with empagliflozin.
Time frame: 6 months
Plasma catecholamine levels
Changes in plasma catecholamine levels at baseline, 1 months and 6 months, in patients with type 2 diabetes treated with empagliflozin.
Time frame: 6 months
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