COVID-19NCT05227170
Impact of Lp299v on Vascular Function in Patients With PASC
A study testing Lactobacillus Plantarum 299v Freeze Dried Capsule and Freeze Dried Potato Starch Capsule in people with COVID-19, run by Medical College of Wisconsin at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 89 years
- Conditions the study is for
- COVID-19
- What is being tested?
- Lactobacillus Plantarum 299v Freeze Dried Capsule and Freeze Dried Potato Starch Capsule
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Apr 2022to 31 Jul 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 89 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ages 18 to 89 years
- 30-180 days post-COVID-19 diagnosis
- PASC diagnosed based on symptom report/expert physician judgement
Who cannot join
- 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 locations and contacts
1 site in 1 country.
United States1 site
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
About this study
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.
Read the detailed 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.
- Conditions
- COVID-19
- Being tested
- Lactobacillus Plantarum 299v Freeze Dried Capsule, Freeze Dried Potato Starch Capsule
- Keywords
- endothelial function, PASC, COVID-19, inflammation, microbiome
- Medical subject headings
- COVID-19, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lactobacillus Plantarum 299v Freeze Dried CapsuleOther
The intervention is a probiotic lactobacillus that is contained in food products in the US
Freeze Dried Potato Starch CapsuleOther
The intervention is potato starch that is freeze dried designed to mimic the lp299v capsule.
| Study group | Role | What they receive |
|---|---|---|
| Lp299v | Experimental | Subjects will consume 20 billion colony forming units of Lp299v (2 capsules) once daily for 8 weeks. Receives: Other: Lactobacillus Plantarum 299v Freeze Dried Capsule |
| Heat-killed placebo control | Placebo comparator | Subjects will consume potato starch (2 capsules) once daily for 8 weeks. Receives: Other: Freeze Dried Potato Starch Capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Brachial Artery Flow Mediated Dilation (FMD%)
This is a measurement of endothelial function in the brachial artery
Measured: 8 weeks
Secondary outcomes (10)
Nitroglycerin-Mediated Vasodilation of the brachial artery (NMD)
Measurement of vascular smooth muscle reactivity
Measured: 8 weeks
Hyperemic Flow Velocity
Measurement of microvascular endothelial function
Measured: 8 weeks
Carotid-Femoral Pulse Wave Velocity (cfPWV)
Measurement of vascular stiffness
Measured: 8 weeks
Percentage of Laser Doppler Signal
Measurement of skin microvascular function
Measured: 8 weeks
interleukin-6
circulating inflammatory marker
Measured: 8 weeks
Stool microbiota alpha diversity
Diversity of bacterial species in the individual microbiome
Measured: 8 weeks
Stool microbiota beta diversity
Differences in bacterial composition between intervention arms
Measured: 8 weeks
Cell-Free Mitochondrial DNA (cf-mtDNA)
Level of circulating cf-mtDNA in the plasma
Measured: 8 weeks
Brachial Artery Resting Diameter
resting diameter of the brachial artery - representative of resting vascular tone
Measured: 8 weeks
Myeloid Cell Population phenotypes
Quantification and identification of mononuclear cell and neutrophil types
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2022
- Study start29 Apr 2022
- Primary completion31 Jul 2025
- Study completion31 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by Medical College of WisconsinThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael E. Widlansky, Medical College of Wisconsin
- Investigators
- Michael E Widlansky, MD, MPH, Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05227170
- Sponsor's protocol ID
- PRO42931
- Status last verified
- Oct 2026
- First submitted
- 27 Jan 2022
- Last updated
- 30 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Lp299v on Vascular Function in Patients With PASC
- ClinicalTrials.gov ID
- NCT05227170
- Acronym / sponsor ID
- PRO42931
- Conditions
- COVID-19
- Keywords
- endothelial function, PASC, COVID-19, inflammation, microbiome
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Study start
- 29 Apr 2022 (actual)
- Primary completion
- 31 Jul 2025 (actual)
- Study completion
- 31 Jul 2027 (estimated)
- First posted
- 7 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lp299v | Experimental | Other: Lactobacillus Plantarum 299v Freeze Dried CapsuleSubjects will consume 20 billion colony forming units of Lp299v (2 capsules) once daily for 8 weeks. |
| Heat-killed placebo control | Placebo comparator | Other: Freeze Dried Potato Starch CapsuleSubjects will consume potato starch (2 capsules) once daily for 8 weeks. |
Who may qualify
- Ages
- 18 to 89 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Ages 18 to 89 years
- 30-180 days post-COVID-19 diagnosis
- PASC diagnosed based on symptom report/expert physician judgement
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lactobacillus Plantarum 299v Freeze Dried CapsuleThe intervention is a probiotic lactobacillus that is contained in food products in the US | Other | Lp299v |
| Freeze Dried Potato Starch CapsuleThe intervention is potato starch that is freeze dried designed to mimic the lp299v capsule. | Other | Heat-killed placebo control |
Primary outcome
Brachial Artery Flow Mediated Dilation (FMD%)
Time frame: 8 weeks
This is a measurement of endothelial function in the brachial artery
10 secondary outcomes
Nitroglycerin-Mediated Vasodilation of the brachial artery (NMD)
Time frame: 8 weeks
Hyperemic Flow Velocity
Time frame: 8 weeks
Carotid-Femoral Pulse Wave Velocity (cfPWV)
Time frame: 8 weeks
Percentage of Laser Doppler Signal
Time frame: 8 weeks
interleukin-6
Time frame: 8 weeks
Stool microbiota alpha diversity
Time frame: 8 weeks
Stool microbiota beta diversity
Time frame: 8 weeks
Cell-Free Mitochondrial DNA (cf-mtDNA)
Time frame: 8 weeks
Brachial Artery Resting Diameter
Time frame: 8 weeks
Myeloid Cell Population phenotypes
Time frame: 8 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2026.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael E Widlansky, MD, MPH principal investigator
Medical College of Wisconsin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Lactobacillus Plantarum 299v Freeze Dried Capsule and Freeze Dried Potato Starch Capsule in people with COVID-19, run by Medical College of Wisconsin at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 30 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Brachial Artery Flow Mediated Dilation (FMD%) (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2026.