Fontan Circulation, Single Ventricle Heart Disease, HFpEF - Heart Failure With Preserved Ejection Fraction
Conditions
Keywords
Fontan, HFpEF, SGLT2 inhibitors
Brief summary
The purpose of this research is to determine whether treatment with the study drug dapagliflozin for 3 months affects peripheral venous pressure at rest and during exercise in adults with failing Fontan circulation.
Interventions
Patient will take a 10mg tablet of Dapagliflozin once daily for 12 weeks
DRUGPlacebo Tablet
Patient will take 10mg placebo tablet once daily for 12 weeks
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed informed consent prior to any study specific procedures 2. History of Fontan procedure 3. Male or female subject 4. Age ≥ 18 5. Symptoms of dyspnea (NYHA II-IV) with no non-cardiac or ischemia explanation 6. Elevated peripheral venous pressure (PVP) at rest or during exercise (≥20 mmHg) ascertained at Visit 1. Patients that have consented to study procedures but do not meet this invasive criterion will be considered as screen failures and will not be randomized.
Exclusion criteria
1. Type I diabetes 2. Any of the following medications: Insulin or Pramlintide, Sandostatin, Akeega (abiraterone acetate), Growth Hormone (Somatogrogon-GHLA), Lithium, Chloroquine, Hydroxychloroquine, Thioctic acid (alpha lipoic acid), Empagliflozin or Canagliflozin 3. Recent hospitalization (\<30 days) or revascularization (\<90 days) 4. Significant valvular heart disease (≥moderate stenosis, \>moderate regurgitation) 5. Significant Fontan obstruction with resting SVC-IVC gradient \>4 mmHg 6. Primary cardiomyopathy (such as amyloid) 7. Dyspnea due to primary lung disease or myocardial ischemia in the opinion of the investigator 8. Severe anemia (hemoglobin \<9 gm/dl) 9. Severe kidney disease (estimated GFR\<30) or liver disease 10. Women of childbearing potential not willing to use a medically accepted method of contraception OR who are currently pregnant (confirmed with positive pregnancy test) or breast feeding. 11. History of serious hypersensitivity reaction to dapagliflozin 12. Subjects on dialysis 13. Subjects with severe liver disease with history of decompensation including ascites or encephalopathy or variceal bleeding 14. Single ventricle heart disease without Fontan palliation 15. Those with a history of Fontan takedown
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peripheral venous pressure (PVP) at rest | Baseline, 12 Weeks | Peripheral venous pressure (PVP) at rest will be determined by Stress Echocardiogram. Peripheral venous pressure (PVP) is measured in millimeters of mercury (mmHg). |
| Peripheral venous pressure (PVP) with feet elevated | Baseline, 12 Weeks | Peripheral venous pressure (PVP) with feet elevated will be determined by Stress Echocardiogram. Peripheral venous pressure (PVP) is measured in millimeters of mercury (mmHg). |
| Peripheral venous pressure (PVP) at 20W exercise | Baseline, 12 Weeks | Peripheral venous pressure (PVP) at 20W exercise will be determined by Stress Echocardiogram. Peripheral venous pressure (PVP) is measured in millimeters of mercury (mmHg). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cardiac output at rest | Baseline, 12 Weeks | Cardiac output measures the amount of blood the heart pumps per minute. It is calculated by Cardiac Output= Oxygen Consumption/(Arterial - Venous Oxygen Content Difference). Cardiac output will be measured in liters per minute (L/min). |
| Cardiac output with exercise | Baseline, 12 Weeks | Cardiac output measures the amount of blood the heart pumps per minute. It is calculated by Cardiac Output= Oxygen Consumption/(Arterial - Venous Oxygen Content Difference). Cardiac output will be measured in liters per minute (L/min). |
| Peak oxygen consumption (VO2) during exercise | Baseline, 12 Weeks | Peak oxygen consumption (VO2) is measured in milliliters of oxygen per minute (mL/min). |
| Change in plasma volume | Baseline, 12 Weeks | Plasma volume will be determined by radiolabeled iodinated albumin (131I, 5-25 μCu) indicator dilution technique (BVA-100 Blood Volume Analyzer, Daxor Corp, NY). Plasma volume will be measured in milliliters (mL). |
| Change in blood volume | Baseline, 12 Weeks | Blood volume will be determined by radiolabeled iodinated albumin (131I, 5-25 μCu) indicator dilution technique (BVA-100 Blood Volume Analyzer, Daxor Corp, NY). Blood volume will be measured in milliliters (mL). |
| SF-36 quality of life (QOL) | Baseline, 12 Weeks | SF-36 quality of life (QOL) questionnaire is a 36-question questionnaire that evaluates a patient's quality of life. The score range is from 0-100, with a higher score reflecting a better quality of life. |
| Change in fat mass | Baseline, 12 Weeks | Fat mass will be determined by Dual Energy X-ray Absorptiometry Scan. Fat mass will be measured in kilograms (kg). |
| Change in fat free mass | Baseline, 12 Weeks | Fat free mass will be determined by Dual Energy X-ray Absorptiometry Scan. Fat free mass will be measured in kilograms (kg). |
Countries
United States
Contacts
CONTACTAmanda Wozniak
CONTACTYusef Maarouf
PRINCIPAL_INVESTIGATORLuke Burchill, M.B.B.S., Ph.D.
Mayo Clinic
Outcome results
None listed