Chronic Kidney Diseases, Heart Failure, Heart Failure With Preserved Ejection Fraction, Kidney Diseases
Conditions
Keywords
kidney, heart failure, kidney diseases
Brief summary
The goal of this study is to better understand the effects of a sodium-glucose transport protein 2 inhibitor, dapagliflozin, added on to standard of care on heart and lung function and circulating metabolites (substances created when our bodies break down food, drugs, or its own tissues) in patients with chronic kidney disease.
Detailed description
This is a 6-month interventional patient-oriented research study of sixty patients with chronic kidney disease (CKD) and evidence of subclinical heart failure with preserved ejection fraction (HFpEF) (estimated glomerular filtration rate \[eGFR\] 25-60 ml/min/1.73m2, absolute left ventricular longitudinal strain \[LVGLS\] \<18% or left atrial reservoir strain (LARS) \< 25% on 2D-speckle tracking echocardiography or meeting 3/5 of the American Society of Echocardiography criteria for diastolic dysfunction: septal e' \<7 cm/sec, lateral e'\<10 cm/sec, average E/e' ratio\>14, left atrial volume index \>34 mL/m2, or peak tricuspid regurgitation velocity \>2.8 m/sec), or peak VO2 Females: ≤ 18 mL/kg/min, peak VO2 Males: ≤ 20 mL/kg/min on cardiopulmonary exercise testing, or lack of augmentation of LVLS or LARS during exercise. Half of the patients will be randomized to receive dapagliflozin for six months as an add-on to standard of care (SOC). Metabolomic testing and cardiac and functional exercise testing will be done at baseline and at six months. The aim of the current study is to investigate whether SGLT2i-induced metabolomic changes are associated with improved cardiac and functional testing ascertained on 2D-speckle tracking echocardiography or cardiopulmonary functional testing at six months.
Interventions
10mg (milligram) tablet to be taken orally once daily for 6 months. Manufacturer: Astrazeneca. Study drug will be stored and dispensed by the Interventional Drug Service Pharmacy at Northwestern University.
Sponsors
Northwestern University
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
30 subjects will be randomized to intervention. 30 subjects will be randomized to standard of care.
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. \>18 years of age 2. eGFR 25-60 ml/min/1,73m2 (eGFR = estimated glomerular filtration rate) 3. On stable doses of diuretics and/or angiotensin converting enzyme inhibitor or angiotensin receptor blocker 4. Evidence of subclinical heart failure with preserved ejection fraction at their pre-exercise echocardiogram (defined as meeting 3/5 of the American Society of Echocardiography (ASE) criteria for diastolic dysfunction \[septal e'\<7 cm/wc, average E/e' ratio\>14, left atrial volume index \>34 mL/m2, and peak TR velocity \>2.8 m/sec\] or absolute left ventricular longitudinal strain \< 18%, left atrial reservoir strain (LARS) \< 25% on 2d speckle tracking echocardiography), lack of augmentation of LVLS or LARS during exercise, or peak VO2 Females: ≤ 18 mL/kg/min, peak VO2 Males: ≤ 20 mL/kg/min on cardiopulmonary exercise testing.
Exclusion criteria
1. presence or history of diabetes 2. coronary revascularization within the last 6 months 3. hemodynamically significant valvular disease 4. significant lung disease requiring home oxygen 5. angina (chest pain) 6. non-revascularized myocardial ischemia 7. systolic BP \<100 or \>180 mmHg 8. pregnancy 9. clinical heart failure symptoms 10. history of systemic disease processes that can cause HFpEF such as amyloidosis or sarcoidosis 11. any musculoskeletal or chronic condition that will interfere with completion of cardiac testing 12. active cancer 13. immunosuppressive therapy 14. baseline or pre-exercise echocardiogram demonstrates a reduced ejection fraction \< 50% 15. currently on sodium glucose cotransporter 2 inhibitor (SGLT2i) therapy 16. Hypersensitivity to a SGLT2i 17. Pre-existing liver disease 18. ALT/AST\> 3x normal (ALT = alanine aminotransferase AST = aspartate aminotransferase) 19. history of recurrent urinary tract infections (in the opinion of the investigator) or a urinary tract infection in the last 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Left ventricular longitudinal strain (LVLS) | 6 months | 2D-speckle tracking echocardiography |
| Peak VO2 (oxygen consumption) | 6 months | Cardiopulmonary exercise stress test |
| Circulating plasma metabolite concentrations | 6 months | Plasma |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Left Atrial Reservoir Strain (LARS) | 6 months | 2D-STE |
| Right ventricular free wall strain | 6 Months | 2D-STE |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORRupal Mehta, MD
Northwestern Univeristy
Outcome results
None listed