ClinicalTrials.Veeva

Menu

Impact of Lp299v on Vascular Function in Patients With PASC

Medical College of Wisconsin logo

Medical College of Wisconsin

Status

Active, not recruiting

Conditions

COVID-19

Treatments

Other: Freeze Dried Potato Starch Capsule
Other: Lactobacillus Plantarum 299v Freeze Dried Capsule

Study type

Interventional

Funder types

Other

Identifiers

NCT05227170
PRO42931

Details and patient eligibility

About

Emerging data show that SARS-CoV-2 infection causes gut microbiome changes strongly associated with Post-Acute Sequelae of SARS-CoV-2 (PASC). The investigators and others have established that an orally ingested probiotic (Lactobacillus plantarum 299v, Lp299v) reduces circulating levels of cell-free mitochondrial DNA (cf-mtDNA), decreases toll-like receptor 9 (TLR9) activation [and downstream interleukin (IL-6)], and improves micro- and macrovascular (brachial artery) endothelial dysfunction [as measured by flow-mediated dilation (FMD%)] in humans. Recently published data also report impaired brachial FMD% and increased vascular stiffness post-SARS-CoV-2 infection. Based on these data, the investigators hypothesize that supplementation with Lp299v will attenuate SARS-CoV-2 associated endothelial dysfunction by reducing cf-mtDNA, TLR9 activation, and inflammation.

Full description

The intestinal immune system plays a critical role in systemic immunity, and its interaction with the systemic immune system plays a crucial role in determining the severity and outcomes of common pulmonary infections. SARS-CoV-2 infection alters the composition and metabolism of the gut microbiome. Greater losses of beneficial species in the human gut microbiome of SARS-CoV-2 patients are associated with severe disease and greater systemic inflammation. These pathological alterations are observed at least 6 months post-infection and are associated with greater residual systemic inflammation and PASC symptoms.

Six weeks of Lp299v supplementation in otherwise healthy smokers reduces circulating levels of the pro-inflammatory IL-6 and reduces monocyte adhesion to endothelial cells. IL-6 is elevated in patients with PASC and strongly correlates with TLR9 activation in disease states with high circulating cf-mtDNA levels. We published trial data showing once daily Lp299v supplementation (20 billion colony forming units/day) in men with coronary artery disease (CAD) improves endothelium-dependent vasodilation in the brachial artery and NO-dependent vasodilation of resistance arterioles from CAD patients. Further, preliminary data suggest Lp299v reduces circulating levels of cf-mtDNA (Fig. 2B). We also published data showing that 6 weeks of Lp299v has a significant anti-inflammatory effect on PBMC gene transcription, with gene ontology analyses indicating Lp299v supplementation inhibits TLR9 activation (z-score -3.48, P<0.0000000023). Combining the evidence that Lp299v reduces (1) circulating cf-mtDNA; (2) TLR9 activation; and (3) IL-6 levels while improving micro- and macrovascular endothelial function make Lp299v an excellent candidate to test as an intervention to improve vascular function in PASC patients.

Therefore, we will recruit subjects ages ≥18-89 who carry a clinical diagnosis of PASC and are within a window of 30-180-day post-acute symptom resolution into an 8-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.

Enrollment

80 estimated patients

Sex

All

Ages

18 to 89 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  • Ages 18 to 89 years
  • 30-180 days post-COVID-19 diagnosis
  • PASC diagnosed based on symptom report/expert physician judgement

Exclusion criteria

  • Antibiotics within four weeks of enrollment
  • History of chronic diseases (renal insufficiency, liver dysfunction, cancer requiring systemic treatment within 3 years of enrollment)
  • History of cognitive impairment/inability to follow study procedures
  • Short gut syndrome, inflammatory bowel disease, or an ileostomy.
  • Subjects currently taking Vitamin K antagonists such as coumadin or warfarin
  • Pregnant at the time of screening
  • Unstable coronary artery disease (new symptoms or event within 30 days of enrollment)
  • Daily alcohol use (may interfere with Lp299v's action)

Trial design

Primary purpose

Basic Science

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

80 participants in 2 patient groups, including a placebo group

Lp299v
Experimental group
Description:
Subjects will consume 20 billion colony forming units of Lp299v (2 capsules) once daily for 8 weeks.
Treatment:
Other: Lactobacillus Plantarum 299v Freeze Dried Capsule
Heat-killed placebo control
Placebo Comparator group
Description:
Subjects will consume potato starch (2 capsules) once daily for 8 weeks.
Treatment:
Other: Freeze Dried Potato Starch Capsule

Trial contacts and locations

1

Loading...

Central trial contact

Ryan Kacala; Michael E Widlansky, MD, MPH

Data sourced from clinicaltrials.gov

Clinical trials

Find clinical trialsTrials by location
© Copyright 2025 Veeva Systems