Cardiovascular Diseases, Hypertension
Conditions
Brief summary
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce CVD events, including incident HF. SGLT2 is a glucose transport protein in the kidneys. Inhibition of this protein results in glucosuria and lower serum blood sugar. The SGLT2i medications were initially approved to treat type 2 diabetes (T2D). In 2015, Zinman et al. published the first large randomized clinical trial (RCT) demonstrating a lower composite CVD outcome in adults with T2D treated with empagliflozin compared to placebo (HR 0.85, 95% CI 0.74-0.99). In the specific case of empagliflozin, the hazard ratio was 0.75 (95% CI 0.65-0.86) for HFrEF 8 and 0.79 (95% CI 0.69-0.90) for HFpEF using a treatment dose of 10mg daily. The purpose of this placebo-controlled, double-blinded, randomized pilot study is to investigate the effect of empagliflozin on left atrial (LA) function in 80 patients who are at risk for heart failure. Participants will be randomized 1:1 to either intake of a 10mg empagliflozin oral tablet or a matching placebo once daily.
Interventions
DRUGempagliflozin
intake of a 10mg empagliflozin oral tablet At visit 1, after randomization, participants will be provided with bottles containing enough study pills for 3 months duration at 1 tablet daily. Participants will start the study drug on the morning following Visit 1. At the 3 month follow up visit, participants will be provided with enough study pills to complete the remaining 6 months of the study.
DRUGPlacebo tablet
intake a placebo oral tablet At visit 1, after randomization, participants will be provided with bottles containing enough study pills for 3 months duration at 1 tablet daily. Participants will start the study drug on the morning following Visit 1. At the 3 month follow up visit, participants will be provided with enough study pills to complete the remaining 6 months of the study.
Sponsors
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
placebo-controlled, double-blinded, randomized pilot study
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>60 years of age * Clinical diagnosis of hypertension * Body mass index ≥30kg/m2 * We will screen for participants with an echocardiogram within 60 days of the baseline visit
Exclusion criteria
* Female participants who are pregnant, lactating, or of child bearing potential * History of type 1 or type 2 diabetes mellitus by medical history or hemoglobin A1c \>7.0% at Visit 1 * Clinical diagnosis of HFpEF or HFrEF by participant self-report or documented in the electronic health record * Any LVEF measure of ≤40% on past echocardiogram * Moderate or severe valve disease on echocardiogram * History of genitourinary infection * eGFR \<60 ml/min/1.73 m2 at Visit 1 * Current treatment with SGLT2 inhibitor, GLP1 agonist, or DPP4 inhibitors * Participants in whom coronary revascularization by either PCI or bypass surgery is being contemplated within 6 months, or who have undergone revascularization in the prior 2 months * Significant allergy or known intolerance to SGLT2 inhibitors or any ingredient in the formulations * Participants currently experiencing any clinically significant or unstable medical condition that might limit their ability to complete the study, or to comply with the requirements of the protocol, including: dermatologic disease, hematological disease, pulmonary disease, hepatic disease, gastrointestinal disease, genitourinary disease, endocrine disease, neurological disease, and psychiatric disease * Any malignancy not considered cured (except basal cell carcinoma of the skin). A participant is considered cured if there has been no evidence of cancer recurrence for the 5 years prior to screening * Participants who have participated in studies of an investigational drug or device within 30 days prior to the screening visit * Inadequate quality echocardiographic images * Unstable coronary syndromes * Major surgery (major according to the investigator's assessment) performed within 90 days prior to Visit 1 or scheduled major elective surgery within 90 days after Visit 1. * Non-English speaking individuals
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| change in LA function | 9 months | LA function will be quantified by assessing LA reservoir, conduit, and contractile strain with 2DE at baseline and 9 months. |
Secondary
| Measure | Time frame |
|---|---|
| change in global longitudinal strain | 9 months |
| change in mass (indexed to body surface area) | 9 months |
| change in E/e' ratio | 9 months |
| change in plasma protein levels: DLK-1 (protein delta homolog 1) | 9 months |
| change in plasma protein levels: GDF15 (growth differentiating factor 15) | 9 months |
| change in plasma protein levels: Spondin-1 | 9 months |
| change in plasma protein levels: IGBPF-7 | 9 months |
| change in left ventricular ejection fraction | 9 months |
| change in plasma protein levels: IGFBP-1 (insulin-like binding factor protein 1) | 9 months |
| change in plasma protein levels: FABP-4 (fatty acid-binding protein 4) | 9 months |
| change in plasma protein levels: CCL16 (C-C motif chemokine 16) | 9 months |
| change in cardiovascular disease biomarker C-reactive protein (CRP) | 3 months and 9 months |
| change in cardiovascular disease biomarker Troponin | 3 months and 9 months |
| change in cardiovascular disease biomarker NT-proBNP | 3 months and 9 months |
| changes in blood pressure ration | 1, 3 and 9 months |
| change in plasma protein levels: THBS-2 (thrombospondin 2) | 9 months |
Countries
United States
Contacts
Primary ContactJulie Dicken, RN
Outcome results
None listed