Effect of an Isolevuglandin Scavenger on Salt Sensitivity of Blood Pressure and Immune Cell Activation in Humans
Vanderbilt University Medical Center
Summary
Hypertension is the leading cause of preventable deaths globally, driven by complications such as myocardial infarction, stroke, heart failure, and kidney disease. Recent updates in hypertension classification by the American Heart Association (AHA) place nearly half of the U.S. population in the hypertensive category. Excess dietary salt is a major risk factor for hypertension, with 50% of hypertensive individuals exhibiting salt-sensitivity of blood pressure (SSBP). SSBP is an independent predictor of cardiovascular events and death. While kidney mechanisms in salt-sensing have been extensively studied, emerging evidence suggests that immune cells can also sense sodium (Na+). This trial hypothesizes that myeloid cell-derived isolevuglandins (IsoLGs) drive endothelial dysfunction, perpetuating the salt-sensitive phenotype. Preliminary data indicate that targeting IsoLGs with the IsoLG scavenger 2-hydroxybenzylamine (2-HOBA) may interrupt this immune-vascular axis, reducing salt sensitivity and associated cardiovascular risks. This phase 2 clinical trial aims to investigate the role of 2-HOBA in modulating immune cell function within blood vessels in hypertensive patients. The study will explore the impact of immunity on salt sensitivity and assess 2-HOBA's potential to reduce endothelial dysfunction, improve immune cell activation, and alleviate SSBP.
Description
Investigators will perform a 12-week randomized, double-blind, placebo-controlled, 2x2 crossover proof-of-concept phase II study with treatment of 2-HOBA in participants previously phenotyped for SSBP. Investigators will randomize people with known SSBP (i.e., 10 mmHg drop in systolic blood pressure from salt-loading to salt-depletion) to treatment with 2-HOBA (500mg) three times a day for 4 weeks, followed by a washout period of 4 weeks, and then placebo for 4 weeks versus placebo then washout then 2-HOBA. Assessments will be obtained at week 0, 4, 8 and 12 per cross-over design above. The in…