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

Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05719714
• Other study ID #: STU00215566
• Secondary ID: K23HL150236
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 16, 2024
• Est. completion date: September 30, 2026

Study information

• Verified date: May 2024
• Source: Northwestern University
• Contact: Rupal Mehta, MD
• Phone: (312) 503-1536
• Email: rupal.mehta[@]northwestern.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: September 30, 2026
• Est. primary completion date: March 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Kidney Diseases
• Heart Failure
• Heart Failure With Preserved Ejection Fraction
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

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.

Locations

Country	Name	City	State
United States	Northwestern University	Chicago	Illinois

Sponsors (3)

Lead Sponsor	Collaborator
Northwestern University	National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

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* Note: There are 37 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Left ventricular longitudinal strain (LVLS)	2D-speckle tracking echocardiography	6 months
Primary	Peak VO2 (oxygen consumption)	Cardiopulmonary exercise stress test	6 months
Primary	Circulating plasma metabolite concentrations	Plasma	6 months
Secondary	Left Atrial Reservoir Strain (LARS)	2D-STE	6 months
Secondary	Right ventricular free wall strain	2D-STE	6 Months

External Links

•   Reference #1 in protocol. CDC National Chronic Kidney Disease Fact Sheet
•   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.