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

NCT ID: NCT05719714

Last Updated: 2025-07-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-16
• Study Completion Date: 2026-09-30

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.

Conditions

Chronic Kidney Diseases; Heart Failure With Preserved Ejection Fraction; Kidney Diseases; Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intervention group

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

Group Type: EXPERIMENTAL

Dapagliflozin 10 MG [Farxiga]

Intervention Type: DRUG

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.

Standard of Care group

Thirty individuals will be randomized to standard of care treatment.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Rupal Mehta

Doctor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rupal Mehta, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern Univeristy

Locations

Northwestern University

Chicago, Illinois, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Rupal Mehta, MD

Role: CONTACT

rupal.mehta@northwestern.edu

(312) 503-1536

Tamara Isakova, MD

Role: CONTACT

tamara.isakova@northwestern.edu

(312) 503-6921

Facility Contacts

Rupal C Mehta, MD

Role: primary

rupal.mehta@northwestern.edu

312-503-1536

Tamara Isakova, MD

Role: backup

tamara.isakova@northwestern.edu

312-926-2000

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Related Links

https://cardiab.biomedcentral.com/articles/10.1186/s12933-017-0569-8

Reference #28 in protocol. Symmetric and asymmetric dimethylarginine as risk markers of cardiovascular disease, all-cause mortality and deterioration in kidney function in persons with type 2 diabetes and microalbuminuria.

Other Identifiers

K23HL150236

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STU00215566

Identifier Type: -

Identifier Source: org_study_id