Effect of Propionic Acid Supplementation on Endothelial Function

Sponsor
Medical College of Wisconsin
Study ID
NCT05135702
Status
Not Yet Recruiting

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Conditions

  • Cardiovascular Diseases
  • Endothelial Dysfunction

Eligibility Criteria

Sex
ALL
Age
40 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

  • Sodium Propionate — DIETARY_SUPPLEMENT
    a 500 mg powder dietary supplement that can be mixed into food or drinks. It will be taken twice daily for four weeks.
  • Placebo — DIETARY_SUPPLEMENT
    a color, size, calorie, and consistency-matched powder dietary supplement that can be mixed into food or drinks. It will be taken twice daily for four weeks.

Study Details

Coronary Artery Disease (CAD) remains a leading cause of morbidity and mortality worldwide despite improved mitigation of traditional risk factors. Large association studies have linked the gut microbiome alterations with inflammation, CAD, and traditional CAD risk factors. Subsequent studies have shown concomitant improvements in gut dysbiosis, inflammation, and cardiometabolic diseases using probiotics and other gut-modulating therapies. To date, many studies have shown a correlative relationship between intestinal bacteria composition and the presence of CAD, or severity of heart attacks, but few have begun to elucidate potential metabolic and immunologic mechanisms. The investigator's recently supplemented Lactobacillus plantarum 299v in men with stable CAD, which improved systemic inflammation and brachial artery flow-mediated dilation (BA-FMD) - a measure of endothelial function and a predictive CAD precursor. Improvement in BA-FMD positively correlated with increased serum propionic acid (PA) concentrations. PA is a gut microbiome-derived short chain fatty acid (SCFA) with known human vascular receptors and implicated in endothelial function, innate immunity, and glucose homeostasis. Whether PA is mediating improvement in endothelial dysfunction or inflammation in the investigator's prior experiment remains unknown. The investigator's objective is to determine whether endothelial cell function is improved by dietary supplementation of sodium propionate in patients with established coronary artery disease. Furthermore, the investigators wish to elucidate to what extent inflammation is reduced by this therapy, by both measuring serum inflammatory markers and by seeing if plasma from treated patients induces anti-inflammatory transcriptomic responses from cultured endothelial cells and peripheral blood mononuclear cells, both of which are involved in atherosclerosis. Specific Aim 1 will determine the impact of dietary PA supplementation on endothelial function and traditional CAD risk factors in patients with CAD. The investigators will utilize ultrasound to assess the percent change in BA-FMD before and after dietary PA supplementation. The extent of endothelium-dependency of these responses will be tested by measuring BA-FMD following nitroglycerin administration. The investigators will also measure markers representative of traditional CAD risk factors, such as lipid levels and HgbA1C. Specific Aim 2 will determine anti-inflammatory changes in vivo and in transcriptomic signatures of cultured EC and PBMCs induced by dietary PA. The investigators will measure changes to systemic serum inflammatory markers involved in atherosclerotic processes using a targeted metabolomics approach, using plasma from the investigator's cohort before and after PA supplementation. Plasma samples will be used to incubate aforementioned cells to compare transcriptomic signatures of cells subjected to pre-supplementation plasma versus post-supplementation plasma. The investigators will use Ingenuity Pathway Analysis to determine changes to inflammatory pathways and i.i.com to determine whether more anti-inflammatory signatures were induced. Specific Aim 3 will determine the impact of PA supplementation on gut microbiome taxonomy and diversity. As an optional additional clinical study activity, the investigators will collect stool samples before and after dietary PA supplementation, subject samples to multiplex 16S RNA sequencing, and calculate the Shannon Diversity Index. This will help us determine changes in individual gut microbiome constituents and diversity of the entire population.

Key Dates

First listed
Nov 26, 2021
Start date
Jul 31, 2027
Status verified
Sep 2025
Primary completion
Jul 31, 2029
Completion
Dec 31, 2029

Study Design

Enrollment
20 participants (estimated)
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE

Arms

  • Experimental: Sodium Propionate First
    Subjects in this arm will consume 500mg sodium propionate powder twice daily for four weeks, mixed into their food/drink. This is followed by four weeks of placebo twice daily.
  • Placebo Comparator: Placebo First
    Subjects in this arm will consume a placebo twice daily for four weeks, mixed into their food/drink. This is followed by four weeks of 500mg sodium propionate powder, twice daily.

Primary Outcome Measure

Change in baseline flow mediated dilation (FMD) at 4 weeks [ Time Frame: baseline and week 4 ]

Central Contacts

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