Impact of Empagliflozin on Functional Capacity in Heart Failure With Preserved Ejection Fraction

Sodium-Glucose Cotransporter-2 (SGLT-2) inhibitors generally and empagliflozin specifically have shown cardiovascular benefits in patients with heart failure (HF), but the underlying mechanisms remain unclear. Empagliflozin use resulted in lower pulmonary artery diastolic pressures in patients with HF, suggesting a beneficial diuretic effect. Other potential mechanisms include increased blood volume, decreased blood pressure, and changes in sympathetic and neuro-hormonal activation.

This study is a single-arm, open label, prospective interventional study of 8 subjects with heart failure with preserved ejection fraction (HFpEF). Before and after 12 weeks of daily empagliflozin, participants with undergo comprehensive invasive exercise testing with a right heart catheter. Our goal is to evaluate the effects of empagliflozin on fitness, assessed by peak VO2, and peak left ventricular filling pressure, assessed by pulmonary capillary pressure at peak exercise.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus; Heart Failure, Diastolic; Heart Failure With Preserved Ejection Fraction
• Intervention / Treatment: Drug: Empagliflozin 10 MG

Detailed Description

This is a single-arm, open label, pilot study of 8 subjects with HFpEF. The subjects will undergo screening tests (exercise stress echo and blood work) to evaluate for potential exclusion criteria and provide familiarization to the exercise protocol. Those included will undergo an echocardiogram and invasive cardiopulmonary exercise test. This involves placement of a right heart catheter in the pulmonary artery and undergoing seated, upright exercise. During the exercise test, the subject's oxygen uptake (VO2), intra-cardiac pressures (right atrial pressure, pulmonary capillary wedge pressure) and cardiac output (Qc) will be measured. The subject will take a dose of empagliflozin in the lab and wait for at least 60 minutes. They will repeat a shortened version of the exercise test in the afternoon. After baseline testing, each subject will take 10mg empagliflozin daily for 12 weeks. They will have repeat blood work (specific electrolytes and renal function) 30 days after starting medication to screen for renal injury. After 12 weeks, they will return for another invasive cardiopulmonary exercise test and echocardiogram.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Dallas, Texas, United States, 75231
      • Institute for Exercise and Environmental Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• adults ages 50-85
• clinical heart failure
• ejection fraction > 50%

Exclusion Criteria:

• previous hypersensitivity or adverse reaction to SGLT-2 inhibitors
• currently treated with SGLT-2 inhibitor
• current or prior ejection fraction <50%
• chronic kidney disease with glomerular filtration rate < 45 ml/kg/min
• unstable coronary artery disease
• significant arrhythmia
• BMI >55 kg/m2
• inability to exercise.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm; This arm of the study will take 10 mg empagliflozin daily for 12 weeks	Drug: Empagliflozin 10 MG; Daily Empagliflozin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Oxygen Uptake	Peak VO2 measured on maximal exercise test	12 weeks
Peak Pulmonary Capillary Wedge Pressure (PCWP)	Peak PCWP, measured at end-expiration, at the end of maximal exercise test	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Endpoints after single dose of empagliflozin	Peak VO2 and peak PCWP will be measured after a single dose of empagliflozin	1 hour
Cardiac Output at Rest and During Exercise		12 weeks
Stroke Volume at Rest and During Exercise		12 weeks
Right Atrial Pressure at Rest and During Exercise		12 weeks
Pulmonary Capillary Wedge Pressure at Rest and During Submaximal Exercise		12 weeks
Left ventricular volumes at rest and during submaximal exercise	Measured by echocardiography	12 weeks
Hemoglobin mass, plasma volume, total blood volume	Measured by Carbon Monoxide Rebreathe	12 weeks
Diastolic parameters at rest and during submaximal exercise	Measured by echocardiography	12 weeks
6 minute walk time		12 weeks

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: Boehringer Ingelheim

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2021
• Primary Completion (Actual): September 20, 2023
• Study Completion (Actual): February 19, 2024

Study Registration Dates

• First Submitted: November 10, 2021
• First Submitted That Met QC Criteria: November 17, 2021
• First Posted (Actual): December 1, 2021

Study Record Updates

• Last Update Posted (Estimated): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Exercise; Invasive Exercise Testing; SGLT-2 Inhibitors
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Heart Failure, Diastolic; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Empagliflozin
• Other Study ID Numbers: STU 2018-0311

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: De-identified data may be made available upon reasonable request

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.: No