Clinical trial NCT05139472: Impact of Empagliflozin on Functional Capacity in Heart Failure with Preserved Ejection Fraction
Official title: Impact of Empagliflozin on Functional Capacity in Heart Failure with Preserved Ejection Fraction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Heart Failure with Preserved Ejection Fraction
Heart Failure, Diastolic
Diabetes Mellitus
Keywords: Exercise
Invasive Exercise Testing
SGLT-2 Inhibitors
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: Boehringer Ingelheim
First posted: 2021-12-01
Enrollment: 8
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single arm, open label trial
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Peak Oxygen Uptake
timeFrame: 12 weeks
measure: Peak Pulmonary Capillary Wedge Pressure (PCWP)
timeFrame: 12 weeks
Secondary outcomes:
measure: Primary Endpoints after single dose of empagliflozin
timeFrame: 1 hour
measure: Cardiac Output at Rest and During Exercise
timeFrame: 12 weeks
measure: Stroke Volume at Rest and During Exercise
timeFrame: 12 weeks
measure: Right Atrial Pressure at Rest and During Exercise
timeFrame: 12 weeks
measure: Pulmonary Capillary Wedge Pressure at Rest and During Submaximal Exercise
timeFrame: 12 weeks
measure: Left ventricular volumes at rest and during submaximal exercise
timeFrame: 12 weeks
measure: Hemoglobin mass, plasma volume, total blood volume
timeFrame: 12 weeks
measure: Diastolic parameters at rest and during submaximal exercise
timeFrame: 12 weeks
measure: 6 minute walk time
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Institute for Exercise and Environmental Medicine
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
Study officials:
References: