Vascular Aging and Lp299v Study

Vascular Aging Clinical Trial

Official title: Impact of Lp299v on Vascular Aging in Healthy Adults

Status Recruiting

Clinical Trial Summary

Emerging data suggest the gut microbiota regulates multiple mechanisms related to vascular aging, but no intervention targeting the gut microbiota has been tested in older adults without cardiovascular risk factors or cardiovascular disease. Early human data suggest an increase in potentially pathological gut metabolites such as trimethylamine-N-oxide (TMAO) are associated with older age, increased vascular stiffness, increased oxidative stress, and reduced nitric oxide (NO) bioavailability as evidenced by impaired endothelium-dependent vasodilation. Based on this data, the investigators hypothesize that supplementation with Lp299v will reverse human vascular aging in healthy older adults free of known traditional cardiovascular risk factors.

Clinical Trial Description

Multiple lines of evidence suggest that aging results in significant changes in the composition and metabolism of the gut microbiota that accelerate mechanisms responsible for vascular aging. Recent work established cross-sectional associations between phenotypically older vasculature (with increased vascular stiffness and impaired brachial endothelium-dependent vasodilation) and age-related alterations on the composition of the gut microbiota and metabolites that are derived from microbial metabolism such as TMAO (trimethylamine-N-oxide), nicotinamide, tryptophan, and purines. Animal data also suggests short-chain fatty acids favorably impact endothelium-dependent vasodilation. SCFAs exert a direct anti-inflammatory effect on mononuclear cells and increase glucagon-like protein 1 (GLP-1) production which activates endothelial nitric oxide synthase (eNOS) and increases NO levels. Taken together, these data suggest aging-related changes in the gut microbiota could adversely affect vascular health through multiple mechanisms, even in the absence of concomitant cardiovascular risk factors.

Six weeks of Lp299v supplementation in 36 otherwise healthy smokers reduced systemic inflammation, as evidenced by reductions in leptin (an adipokine that stimulates IL-6 production) and IL-6 levels, reduced monocyte adhesion to endothelial cells, and reduced circulating fibrinogen levels (elevated in the setting of inflammation). In addition, Lp299v supplementation reduced oxidative stress based on reduced urinary F2-isoprostanes and had a modest lowering effect on systolic blood pressure.

The investigators will recruit 20 healthy older adults (10 men, 10 women ages 50 or older) without traditional cardiac risk factors or prevalent cardiovascular disease and randomize subjects into a 6-week, double-blind, randomized, placebo-controlled clinical trial of Lp299v supplementation. Measurements of micro-and macrovascular function, systemic inflammation, and stool microbiota composition will be made. ;

Related Conditions & MeSH terms

• Vascular Aging

• NCT number: NCT05296395
• Study type: Interventional
• Source: Medical College of Wisconsin
• Contact: Michael E Widlansky, MD
• Phone: 414-955-6759
• Email: mwidlans@mcw.edu
• Status: Recruiting
• Phase: N/A
• Start date: February 1, 2023
• Completion date: September 22, 2027