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

November 14, 2023 updated by: Rupal Mehta, Northwestern University
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

60

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60607
        • Recruiting
        • Northwestern University
        • Contact:
        • Contact:
        • Principal Investigator:
          • Rupal Mehta, MD
        • Sub-Investigator:
          • Tamara Isakova, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 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:

  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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Left ventricular longitudinal strain (LVLS)
Time Frame: 6 months
2D-speckle tracking echocardiography
6 months
Peak VO2 (oxygen consumption)
Time Frame: 6 months
Cardiopulmonary exercise stress test
6 months
Circulating plasma metabolite concentrations
Time Frame: 6 months
Plasma
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Left Atrial Reservoir Strain (LARS)
Time Frame: 6 months
2D-STE
6 months
Right ventricular free wall strain
Time Frame: 6 Months
2D-STE
6 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northwestern University

Collaborators

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

Investigators

  • Principal Investigator: Rupal Mehta, MD, Northwestern Univeristy

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2023

Primary Completion (Estimated)

September 1, 2026

Study Completion (Estimated)

September 1, 2026

Study Registration Dates

First Submitted

January 31, 2023

First Submitted That Met QC Criteria

January 31, 2023

First Posted (Actual)

February 9, 2023

Study Record Updates

Last Update Posted (Estimated)

November 16, 2023

Last Update Submitted That Met QC Criteria

November 14, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STU00215566
  • K23HL150236 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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