Enhancing Parasympathetic Activity to Improve Endothelial Dysfunction, Vascular Oxidative Stress in African Americans
Status:
Recruiting
Trial end date:
2028-12-31
Target enrollment:
Participant gender:
Summary
Specific Aim 1: To test the hypothesis that prolonged (3-month) treatment with galantamine
inhibits NADPH IsoLG-protein adducts formation and improves markers of endothelial cell (EC)
dysfunction in AAs.
Aim 1a: The investigators will determine if galantamine inhibits NADPH IsoLG-protein adducts
formation, superoxide production, and immune cell activation compared to placebo.
For this purpose, the investigators will study peripheral blood mononuclear cell (PBMC), a
critical source of systemic oxidative stress, collected from study participants.
Aim 1b: The investigators will determine if galantamine reduces intracellular Iso-LGs,
ICAM-1, and 3-nitrotyrosine, a marker of vascular oxidative stress, in ECs harvested from
study participants.
Specific Aim 2: To determine if prolonged (3-month) treatment with galantamine improves
endothelial dysfunction as measured by vascular reactivity in AAs. The investigators will
measure vascular reactivity in response to ischemia in two vascular beds: (a) in conduit
arteries (brachial artery) using brachial artery diameter flow-mediated dilation (FMD), and
(b) in the microvasculature (MBV) using contrast-enhanced ultrasonography in skeletal muscle.
This proposal will study a novel mechanism that could alter the oxidative and immunogenic
responses that contributes to endothelial dysfunction in AAs and will offer a potential
pathway for the development of more effective therapies aimed at decreasing the progression
of endothelial dysfunction to cardiovascular disease in this population.