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

Northwestern University2 sites in 1 country60 target enrollmentJanuary 16, 2024

ConditionsChronic Kidney Diseases Kidney Diseases Heart Failure

InterventionsDapagliflozin 10 MG [Farxiga]

DrugsDapagliflozin 10 MG [Farxiga]

Overview

Phase: Phase 1
Intervention: Standard of Care group
Conditions: Chronic Kidney Diseases
Sponsor: Northwestern University
Enrollment: 60
Locations: 2
Primary Endpoint: Circulating plasma metabolite concentrations
Status: Recruiting
Last Updated: 19 days ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

January 16, 2024

End Date

September 30, 2026

Last Updated

19 days ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Northwestern University

Responsible Party

Principal Investigator

Rupal Mehta

Doctor of Medicine

Northwestern University

Eligibility Criteria

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 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

•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
•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