Heart Failure, Obesity
Conditions
Keywords
Renal function, Glucose intolerance, Lipid metabolism
Brief summary
The aim of this trial is to assess the effect of Empagliflozin on lipid and glucose metabolism as well as volume homeostasis and renal function in elderly and obese patients with increased risk of developing heart failure. No history of established heart failure or diabetes is allowed. The primary hypotheses are that 6 months treatment with Empagliflozin 10 mg a day will: 1) decrease epicardial adipose tissue volume, and 2) reduce estimated extracellular volume compared with placebo.
Detailed description
The Empire Prevent: Metabolic is a part of the Empire Prevent Trial Program, which also comprises the Empire Prevent: Cardiac. The Empire Prevent: Metabolic is designed to enroll at least 120 patients.
Interventions
DRUGEmpagliflozin 10 MG
Patients are randomized 1:1 to receive either Empagliflozin or matching placebo for 180 days
DRUGPlacebo
Placebo matches the active drug in appearance, odor and labelling.
Sponsors
Danish Heart Foundation
Herlev and Gentofte Hospital
University Hospital Bispebjerg and Frederiksberg
Hillerod Hospital, Denmark
Rigshospitalet, Denmark
Jacob Moller
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Parallel Assignment
Eligibility
Sex/Gender
ALL
Age
60 Years to 84 Years
Healthy volunteers
No
Inclusion criteria
* Body mass index \>28kg/m2 * Age 60-84 years * Established risk factor for developing heart failure, defined as at least one of the following: * hypertension * ischemic heart disease * stroke/transient cerebral ischemia * chronic kidney disease (eGFR 30-45ml/min/1.73m2)
Exclusion criteria
* Diabetes mellitus type 1 or 2 (no medical history, no antidiabetic treatment) * Heart failure with reduced ejection fraction (LVEF \<40%) * Inability to perform exercise test * Dementia * Severe non-compliance * Substance abuse * Severe chronic obstructive pulmonary disease (FEV1\<50% expected value) * Permanent atrial fibrillation * GFR \<30 ml/min/1,73m2 * Severe peripheral artery disease * Cancer treatment within one year beside prostate cancer and basal cell carcinoma * Severe aortic or mitral valve disease * Pregnancy or breastfeeding * Acute hospital admission within 30 days * Participation in other pharmacological study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ventricular epicardial adipose tissue (EAT) mass | 180 days | Between-group difference in the change of EAT mass assessed by cardiac magnetic resonance imaging (MRI) |
| Estimated extracellular volume (eECV) | 180 days | Between-group difference in the change of eECV assessed by 99mTc-DTPA clearance (technetium-99mTc-diethylenetriaminepentaacetic acid) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total epicardial adipose tissue (EAT) volume | 180 days | Between-group difference in the change of EAT mass assessed by cardiac magnetic resonance imaging (MRI) |
| Plasma volume | 180 days | Between-group difference in the change of estimated plasma volume assessed by hematocrit and hemoglobin |
| Right ventricular end-diastolic volume index, RVEDVI | 180 days | Between-group difference in the change of RVEDVI assessed by cardiac MRI |
| Total pericardial adipose tissue volume | 180 days | Between-group difference in the change of pericardial adipose tissue volume assessed by cardiac MRI |
Other
| Measure | Time frame | Description |
|---|---|---|
| Kidney function (estimated) | 180 days | Between-group difference in the change of estimated glomerular filtration rate (eGFR) based on the chronic kidney disease epidemiology collaboration (CKD-EPI) estimation |
| Kidney function (measured) | 180 days | Between-group difference in the change of glomerular filtration rate assessed by 99mTc-DTPA clearance |
| Erythropoietin | 180 days | Between-group difference in the change of erythropoietin |
| Body composition | 180 days | Between-group difference in the change in body composition assessed by dual energy x-ray absorptiometry (DXA) scan |
| Glucose tolerance | 180 days | Between-group difference in the change of glucose metabolism assessed by oral glucose tolerance test |
| Exploratory outcome: fat tissue gene expression | 180 days | Between-group difference in fat tissue gene expression assessed by Western Blot |
| Exploratory outcome: oxidative stress and inflammation. | 180 days | Between-group difference in biomarkers of oxidative stress and inflammation. |
| Ketone bodies | 180 days | Between-group difference in the change of ketone supply to the heart assessed by blood ketones |
| Urine albumin/creatinine ratio | 180 days | Between-group difference in the change of urine albumin/creatinine ratio |
| Uric acid | 180 days | Between-group difference in the change of uric acid |
Countries
Denmark
Outcome results
None listed