RECRUITING

SGLT2i and KNO3 in HFpEF - The SAK HFpEF Trial

Conditions

Heart Failure With Preserved Ejection Fraction

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This study will test whether pharmacologic agents that may improve mitochondrial function and energy fuel metabolism \[Empagliflozin (Empa)\], with and without additional supplements that increase perfusion and fatty acid oxidation \[Potassium Nitrate (KNO3)\], improve submaximal exercise endurance and skeletal muscle oxidative phosphorylation capacity (SkM OxPhos) in participants with Heart Failure with Preserved Ejection Fraction (HFpEF).

Official Title

SGLT2i and KNO3 in HFpEF - The SAK HFpEF Trial

Quick Facts

Study Start:2022-01-24

Study Completion:2026-03-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05138575

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.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. NYHA Class II-III symptoms 2. Left ventricular ejection fraction \>= 50% 3. Stable medical condition for at least 2 weeks, as per investigator judgment 4. Prior or current evidence for elevated filling pressures as follows: 1. Mitral early (E)/septal tissue annular (e') velocity ratio \> 8, in the context of a septal e' velocity \<=7 cm/s or a lateral e' \<= 10 cm/s, in addition to one of the following: i. Large left atrium (LA volume index \> 34 mL/m2), ii. Chronic loop diuretic use for control of symptoms, iii. Elevated natriuretic peptides within the past year (e.g. NTproBNP \> 125 pg/mL in sinus rhythm or \> 375 pg/mL if in atrial fibrillation) 2. Mitral E/e' ratio \> 14 at rest or during exercise 3. Elevated invasively-determined filling pressures previously (resting left ventricular end-diastolic pressure \>= 16 mm Hg or pulmonary capillary wedge pressure \>= 15 mmHg; or PCWP/LVEDP \>= 25 mmHg with exercise) 4. Prior episode of acute heart failure requiring IV diuretics	1. Age \<18 years old 2. Pregnancy: Women of childbearing potential will undergo a urine pregnancy test during the screening visit. 3. Treatment with organic nitrates or phosphodiesterase inhibitors that cannot be interrupted 4. Uncontrolled atrial fibrillation, as defined by a resting atrial fibrillation heart rate \> 100 beats per minute at the time of the baseline assessment 5. Hemoglobin \< 10 g/dL 6. Subject inability/unwillingness to exercise 7. Moderate or greater left sided valvular disease (mitral regurgitation, aortic stenosis, aortic regurgitation), mild or greater mitral stenosis, severe right-sided valvular disease 8. Known hypertrophic, infiltrative, or inflammatory cardiomyopathy 9. Clinically significant pericardial disease, as per investigator judgment 10. Current angina due to clinically significant epicardial coronary disease, as per investigator judgment 11. Acute coronary syndrome or coronary intervention within the past 2 months 12. Primary pulmonary artery hypertension (WHO Group 1 Pulmonary Arterial Hypertension) 13. Clinically significant lung disease as defined by: Chronic Obstructive Pulmonary Disease Stage III or greater GOLD criteria (FEV1\<50%), treatment with oral steroids within the past 6 months for an exacerbation of obstructive lung disease, current use of supplemental oxygen aside from nocturnal oxygen for the treatment of obstructive sleep apnea. * Desaturation to \<90% on the baseline maximal effort cardiopulmonary exercise test will also be grounds for exclusion 14. Clinically-significant ischemia, as per investigator's judgement, on stress testing without either (1) subsequent revascularization, (2) an angiogram demonstrating the absence of clinically significant epicardial coronary artery disease, as per investigator judgment; (3) a follow-up 'negative' stress test, particularly when using a more specific technique (i.e., a negative perfusion imaging test following a 'positive' ECG stress test) * Exercise-induced regional wall motion abnormalities on the echocardiographic assessment during the baseline maximal effort cardiopulmonary exercise test will also be exclusionary 15. Left ventricular ejection fraction \< 45% on a prior echocardiogram or cardiac MRI 16. Significant liver disease impacting synthetic function or volume control (ALT/AST \> 3x ULN, Albumin \< 3.0 g/dL) 17. eGFR \< 30 mL/min/1.73m\^2. 18. Methemoglobin \> 5% 19. Serum potassium \> 5.0 mEq/L on baseline testing 20. Type I Diabetes 21. History of ketoacidosis 22. Current use of or prior intolerance to an SGLT2i 23. Ongoing maintenance of a 'Ketogenic Diet' (low carbohydrate, high fat) 24. Allergy to beets 25. Severe right ventricular dysfunction 26. Baseline resting seated systolic blood pressure \> 180 mmHg or \< 100 mmHg 27. Orthostatic blood pressure response to the transition from supine to standing (\>20 mmHg reduction in systolic blood pressure 2-3 minutes after standing, or a fall in SBP to \< 90 mmHg) 28. Active participation in another study that utilizes an investigational agent (observational studies/registries allowed) 29. Any condition that, in the opinion of the investigator, will interfere with the completion of the study. This may include comorbid or psychiatric conditions that may impede successful completion of the protocol, or logistical concerns (e.g. inability to travel to the exercise unit).

Inclusion Criteria

Exclusion Criteria

1. NYHA Class II-III symptoms
2. Left ventricular ejection fraction \>= 50%
3. Stable medical condition for at least 2 weeks, as per investigator judgment
4. Prior or current evidence for elevated filling pressures as follows:
1. Mitral early (E)/septal tissue annular (e') velocity ratio \> 8, in the context of a septal e' velocity \<=7 cm/s or a lateral e' \<= 10 cm/s, in addition to one of the following: i. Large left atrium (LA volume index \> 34 mL/m2), ii. Chronic loop diuretic use for control of symptoms, iii. Elevated natriuretic peptides within the past year (e.g. NTproBNP \> 125 pg/mL in sinus rhythm or \> 375 pg/mL if in atrial fibrillation)
2. Mitral E/e' ratio \> 14 at rest or during exercise
3. Elevated invasively-determined filling pressures previously (resting left ventricular end-diastolic pressure \>= 16 mm Hg or pulmonary capillary wedge pressure \>= 15 mmHg; or PCWP/LVEDP \>= 25 mmHg with exercise)
4. Prior episode of acute heart failure requiring IV diuretics

1. Age \<18 years old
2. Pregnancy: Women of childbearing potential will undergo a urine pregnancy test during the screening visit.
3. Treatment with organic nitrates or phosphodiesterase inhibitors that cannot be interrupted
4. Uncontrolled atrial fibrillation, as defined by a resting atrial fibrillation heart rate \> 100 beats per minute at the time of the baseline assessment
5. Hemoglobin \< 10 g/dL
6. Subject inability/unwillingness to exercise
7. Moderate or greater left sided valvular disease (mitral regurgitation, aortic stenosis, aortic regurgitation), mild or greater mitral stenosis, severe right-sided valvular disease
8. Known hypertrophic, infiltrative, or inflammatory cardiomyopathy
9. Clinically significant pericardial disease, as per investigator judgment
10. Current angina due to clinically significant epicardial coronary disease, as per investigator judgment
11. Acute coronary syndrome or coronary intervention within the past 2 months
12. Primary pulmonary artery hypertension (WHO Group 1 Pulmonary Arterial Hypertension)
13. Clinically significant lung disease as defined by: Chronic Obstructive Pulmonary Disease Stage III or greater GOLD criteria (FEV1\<50%), treatment with oral steroids within the past 6 months for an exacerbation of obstructive lung disease, current use of supplemental oxygen aside from nocturnal oxygen for the treatment of obstructive sleep apnea.
* Desaturation to \<90% on the baseline maximal effort cardiopulmonary exercise test will also be grounds for exclusion
14. Clinically-significant ischemia, as per investigator's judgement, on stress testing without either (1) subsequent revascularization, (2) an angiogram demonstrating the absence of clinically significant epicardial coronary artery disease, as per investigator judgment; (3) a follow-up 'negative' stress test, particularly when using a more specific technique (i.e., a negative perfusion imaging test following a 'positive' ECG stress test)
* Exercise-induced regional wall motion abnormalities on the echocardiographic assessment during the baseline maximal effort cardiopulmonary exercise test will also be exclusionary
15. Left ventricular ejection fraction \< 45% on a prior echocardiogram or cardiac MRI
16. Significant liver disease impacting synthetic function or volume control (ALT/AST \> 3x ULN, Albumin \< 3.0 g/dL)
17. eGFR \< 30 mL/min/1.73m\^2.
18. Methemoglobin \> 5%
19. Serum potassium \> 5.0 mEq/L on baseline testing
20. Type I Diabetes
21. History of ketoacidosis
22. Current use of or prior intolerance to an SGLT2i
23. Ongoing maintenance of a 'Ketogenic Diet' (low carbohydrate, high fat)
24. Allergy to beets
25. Severe right ventricular dysfunction
26. Baseline resting seated systolic blood pressure \> 180 mmHg or \< 100 mmHg
27. Orthostatic blood pressure response to the transition from supine to standing (\>20 mmHg reduction in systolic blood pressure 2-3 minutes after standing, or a fall in SBP to \< 90 mmHg)
28. Active participation in another study that utilizes an investigational agent (observational studies/registries allowed)
29. Any condition that, in the opinion of the investigator, will interfere with the completion of the study. This may include comorbid or psychiatric conditions that may impede successful completion of the protocol, or logistical concerns (e.g. inability to travel to the exercise unit).

Contacts and Locations

Study Contact

Melissa Fernando

CONTACT

2672536141

fernand@Pennmedicine.upenn.edu

Cassandra Demastus, CRNP

CONTACT

Cassandra.Demastus@Pennmedicine.upenn.edu

Principal Investigator

Payman Zamani, MD

PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Study Locations (Sites)

University of Pennsylvania Health System

Philadelphia, Pennsylvania, 19104

United States

Collaborators and Investigators

Sponsor: University of Pennsylvania

Payman Zamani, MD, PRINCIPAL_INVESTIGATOR, University of Pennsylvania

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 Registration Dates

Study Start Date2022-01-24

Study Completion Date2026-03-01

Study Record Updates

Study Start Date2022-01-24

Study Completion Date2026-03-01

Terms related to this study

Additional Relevant MeSH Terms

Heart Failure With Preserved Ejection Fraction