Effect of Dapagliflozin on Metabolomics and Cardiac Mechanics in Chronic Kidney Disease

Sponsor

Northwestern University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05719714

Collaborator

National Institutes of Health (NIH) (NIH), National Heart, Lung, and Blood Institute (NHLBI) (NIH)

Enrollment

Location

Arms

42.1

Anticipated Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Diseases Heart Failure With Preserved Ejection Fraction Kidney Diseases Heart Failure	Drug: Dapagliflozin 10 MG [Farxiga]	Phase 1/Phase 2

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% on 2D-speckle tracking echocardiography or meeting any 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). 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

30 subjects will be randomized to intervention. 30 subjects will be randomized to standard of care.30 subjects will be randomized to intervention. 30 subjects will be randomized to standard of care.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Effect of Dapagliflozin on Metabolomics and Cardiac Mechanics in Chronic Kidney Disease

Anticipated Study Start Date :

Mar 1, 2023

Anticipated Primary Completion Date :

Sep 1, 2026

Anticipated Study Completion Date :

Sep 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention group Thirty individuals will be randomized to dapagliflozin 10mg to be taken daily for six months.	Drug: Dapagliflozin 10 MG [Farxiga] 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.
No Intervention: Standard of Care group Thirty individuals will be randomized to standard of care treatment.

Arm

Intervention/Treatment

Experimental: Intervention group

Thirty individuals will be randomized to dapagliflozin 10mg to be taken daily for six months.

Drug: Dapagliflozin 10 MG [Farxiga]

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.

No Intervention: Standard of Care group

Thirty individuals will be randomized to standard of care treatment.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

Left Atrial Reservoir Strain (LARS) [6 months]
2D-STE
Right ventricular free wall strain [6 Months]
2D-STE

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

18 years of age
eGFR 25-60 ml/min/1,73m2 (eGFR = estimated glomerular filtration rate)
On stable doses of diuretics and/or angiotensin converting enzyme inhibitor or angiotensin receptor blocker
Evidence of subclinical heart failure with preserved ejection fraction at their pre-exercise echocardiogram (defined as meeting any 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%)

Exclusion Criteria:

presence or history of diabetes
coronary revascularization within the last 6 months
hemodynamically significant valvular disease
significant lung disease requiring home oxygen
angina (chest pain)
non-revascularized myocardial ischemia
systolic BP <100 or >180 mmHg
pregnancy
clinical heart failure symptoms
history of systemic disease processes that can cause HFpEF such as amyloidosis or sarcoidosis
any musculoskeletal or chronic condition that will interfere with completion of cardiac testing
active cancer
immunosuppressive therapy
baseline or pre-exercise echocardiogram demonstrates a reduced ejection fraction </= 50%
currently on sodium glucose cotransporter 2 inhibitor (SGLT2i) therapy
Hypersensitivity to a SGLT2i
Pre-existing liver disease
ALT/AST> 3x normal (ALT = alanine aminotransferase AST = aspartate aminotransferase)
history of recurrent urinary tract infections (in the opinion of the investigator) or a urinary tract infection in the last 3 months