RecruitingPhase 1Phase 2NCT05719714

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


Sponsor

Northwestern University

Enrollment

60 participants

Start Date

Jan 16, 2024

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 18 YearsMax Age: 85 Years

Inclusion Criteria4

  • \>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 Criteria19

  • 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

Interventions

DRUGDapagliflozin 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(1)

Northwestern University

Chicago, Illinois, United States

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NCT05719714


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