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

Sponsor

University of Texas Southwestern Medical Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT05139472

Collaborator

Boehringer Ingelheim (Industry)

Enrollment

Locations

Arm

25.7

Anticipated Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure With Preserved Ejection Fraction Heart Failure, Diastolic Diabetes Mellitus	Drug: Empagliflozin 10 MG	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

8 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Single arm, open label trialSingle arm, open label trial

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 9, 2021

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Peak Oxygen Uptake [12 weeks]
Peak VO2 measured on maximal exercise test
Peak Pulmonary Capillary Wedge Pressure (PCWP) [12 weeks]
Peak PCWP, measured at end-expiration, at the end of maximal exercise test

Secondary Outcome Measures

Primary Endpoints after single dose of empagliflozin [1 hour]
Peak VO2 and peak PCWP will be measured after a single dose of empagliflozin
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 [12 weeks]
Measured by echocardiography
Hemoglobin mass, plasma volume, total blood volume [12 weeks]
Measured by Carbon Monoxide Rebreathe
Diastolic parameters at rest and during submaximal exercise [12 weeks]
Measured by echocardiography
6 minute walk time [12 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Institute for Exercise and Environmental Medicine	Dallas	Texas	United States	75231
2	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390