Clinical trial NCT06507657: Effect of Empagliflozin on Left Atrial Function in Adults at Risk for Heart Failure
Official title: Effect of Empagliflozin on Left Atrial Function in Adults at Risk for Heart Failure
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Hypertension
Cardiovascular Diseases
Lead sponsor: University of Minnesota
Sponsor class: OTHER
First posted: 2024-07-18
Enrollment: 80
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: placebo-controlled, double-blinded, randomized pilot study
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: change in LA function
timeFrame: 9 months
Secondary outcomes:
measure: change in left ventricular ejection fraction
timeFrame: 9 months
measure: change in global longitudinal strain
timeFrame: 9 months
measure: change in mass (indexed to body surface area)
timeFrame: 9 months
measure: change in E/e' ratio
timeFrame: 9 months
measure: change in plasma protein levels: DLK-1 (protein delta homolog 1)
timeFrame: 9 months
measure: change in plasma protein levels: GDF15 (growth differentiating factor 15)
timeFrame: 9 months
measure: change in plasma protein levels: Spondin-1
timeFrame: 9 months
measure: change in plasma protein levels: IGBPF-7
timeFrame: 9 months
measure: change in plasma protein levels: THBS-2 (thrombospondin 2)
timeFrame: 9 months
measure: change in plasma protein levels: IGFBP-1 (insulin-like binding factor protein 1)
timeFrame: 9 months
measure: change in plasma protein levels: FABP-4 (fatty acid-binding protein 4)
timeFrame: 9 months
measure: change in plasma protein levels: CCL16 (C-C motif chemokine 16)
timeFrame: 9 months
measure: change in cardiovascular disease biomarker C-reactive protein (CRP)
timeFrame: 3 months and 9 months
measure: change in cardiovascular disease biomarker Troponin
timeFrame: 3 months and 9 months
measure: change in cardiovascular disease biomarker NT-proBNP
timeFrame: 3 months and 9 months
measure: changes in blood pressure ration
timeFrame: 1, 3 and 9 months
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
Study officials:
affiliation: University of Minnesota
name: Jeremy Van't Hof, MD
role: PRINCIPAL_INVESTIGATOR
References: