The goal of this clinical trial is to examine whether empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, improves vascular and autonomic function in adults with prehypertension. The main questions this clinical trial aims to answer are: 1. Does empagliflozin improve endothelial function? 2. Does empagliflozin improve sympathetic nervous system function? This clinical trial employs a double-blind, placebo-controlled crossover study lasting up to 6 weeks for participants with prehypertension and up to 2 weeks for normotensive participants. Participants with prehypertension will take empagliflozin or placebo for 2 weeks, separated by a 2-week washout. Normotensive participants will complete baseline, pre-treatment visits only and will serve as a control group.
Prehypertension is recognized clinically as a precursor to hypertension, an independent predictor of cardiovascular disease (CVD) risk. Vascular and sympathetic nervous system dysfunction are non-traditional risk factors contributing to increased CVD risk that are mediated, in part, by systemic inflammation and oxidative stress. Targeting vascular and sympathetic nervous system function represents a therapeutic strategy for mitigating CVD risk in prehypertension. Sodium-glucose cotransporter-2 (SGLT2) inhibitors (e.g., empagliflozin) have emerged as a transformative therapeutic class with robust anti-inflammatory and antioxidant properties. The efficacy of SGLT2 inhibitors to improve vascular and sympathetic nervous system function through reductions in pro-inflammatory and improved redox balance have yet to be investigated in prehypertension. In this randomized, double-blind, placebo-controlled clinical trial, the investigators seek to utilize integrative methods for evaluating vascular and sympathetic nervous system function following 2-week treatment with empagliflozin. Understanding the mechanisms underpinning increased CVD risk in prehypertension will inform us about specific pharmacological prevention strategies in this ever-growing clinical population.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
100
Oral ingestion for 2 weeks
Oral placebo for 2 weeks.
Integrative Neurovascular Physiology Laboratory - University of Iowa
Iowa City, Iowa, United States
Macrovascular endothelial function as assessed by brachial artery flow-mediated dilation (FMD)
The brachial artery will be imaged using high-resolution Doppler ultrasound at baseline and following a period of forearm blood-flow occlusion induced by an inflatable blood pressure cuff. FMD will be calculated as the percentage (%) increase in brachial artery diameter from baseline following cuff release, reflecting the ability of the brachial artery to dilate in response to increased blood flow and shear stress. Higher FMD values indicate greater endothelium-dependent vasodilatory function.
Time frame: At the end of each 2-week treatment period
Sympathetic nervous system function as assessed by muscle sympathetic nerve activity
Muscle sympathetic nerve activity (MSNA) will be measured using microneurography, in which a recording electrode will be inserted into a nerve of the lower leg to directly record sympathetic nerve activity. Sympathetic bursts will quantified as burst frequency (bursts/min) and burst incidence (bursts/100 heartbeats). Higher values indicate greater MSNA sympathetic nerve activity.
Time frame: At the end of each 2-week treatment period
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