Probiotics for Long COVID Symptoms

Overseen by Michael E Widlansky

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Medical College of Wisconsin

Must not be taking: Vitamin K antagonists

Disqualifiers: Antibiotics, Chronic diseases, Cognitive impairment, others

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests whether taking a probiotic called Lp299v can help people who have long-term symptoms after COVID-19. The probiotic aims to reduce inflammation and improve blood vessel function. Adults aged 18-89 with these symptoms will take the supplement for a period of time to see if it helps. Probiotics have shown benefits in a variety of diseases, including respiratory infections, and may be beneficial in the adjunctive treatment of COVID-19.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking antibiotics, Vitamin K antagonists like coumadin or warfarin, or if you have certain health conditions. It's best to discuss your medications with the trial team.

What data supports the effectiveness of the treatment Lp299v for Long COVID symptoms?

Research shows that Lactobacillus plantarum, a component of Lp299v, can boost immune responses and reduce inflammation, which may help in managing COVID-19 symptoms. Additionally, probiotics have been shown to shorten the duration of COVID-19 symptoms and improve immune function, suggesting potential benefits for Long COVID. ^{1 2 3 4 5}

Is Lactobacillus plantarum 299v safe for human consumption?

Lactobacillus plantarum 299v (also known as Lp299v) is considered safe for human consumption, as it has been studied in over 60 human clinical trials and does not cause antibiotic resistance. It is used in various food products and dietary supplements, and has been shown to survive the conditions in the human gut. ^{6 7 8 9 10}

How does the treatment Lp299v differ from other treatments for Long COVID symptoms?

Lp299v (Lactiplantibacillus plantarum 299v) is unique because it is a probiotic that may help rebalance the gut microbiome, which can influence immune responses through the gut-lung axis. Unlike other treatments, it potentially enhances the body's natural immune response and reduces inflammation, which could be beneficial for managing Long COVID symptoms. ^{2 4 11 12 13}

Research Team

Michael E Widlansky

Principal Investigator

Medical College of Wisconsin

Eligibility Criteria

This trial is for adults aged 18-89 who have had COVID-19 and are experiencing lingering symptoms known as PASC. They must be within 30 to 180 days post-diagnosis. People with daily alcohol use, recent antibiotics, blood thinner usage like warfarin, pregnancy, cognitive issues preventing study compliance, unstable heart disease or certain chronic conditions can't participate.

Inclusion Criteria

I was diagnosed with COVID-19 between 30 to 180 days ago.

I am between 18 and 89 years old.

I have been diagnosed with long COVID by a doctor.

Exclusion Criteria

Pregnant at the time of screening

You drink alcohol every day, which could affect the way the study drug works.

I am currently taking blood thinners like coumadin or warfarin.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Lp299v or placebo supplementation for 8 weeks

8 weeks

Weekly visits (in-person or virtual) for monitoring and data collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Lp299v (Probiotic)

Trial Overview The trial tests if a probiotic called Lactobacillus plantarum (Lp299v) in capsule form can improve blood vessel function in those with PASC by reducing inflammation and immune system activation compared to a placebo made of potato starch capsules.

Participant Groups

Group I: Lp299v Experimental Treatment 1 Intervention

Subjects will consume 20 billion colony forming units of Lp299v (2 capsules) once daily for 8 weeks.

Group II: Heat-killed placebo control Placebo Group 1 Intervention

Subjects will consume potato starch (2 capsules) once daily for 8 weeks.

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Dr. Joseph E. Kerschner

Medical College of Wisconsin

Chief Medical Officer since 2011

MD, specific institution not identified

Dr. John R. Raymond, Sr.

Medical College of Wisconsin

Chief Executive Officer since 2010

MD from the Medical University of South Carolina

Findings from Research

In a study of 300 symptomatic COVID-19 outpatients, those taking a specific probiotic formula achieved complete remission of symptoms at a significantly higher rate (53.1%) compared to the placebo group (28.1%), indicating the probiotic's potential efficacy in managing COVID-19 symptoms.

The probiotic supplementation was well-tolerated and not only reduced viral load and lung infiltrates but also increased specific immune responses against SARS-CoV-2, suggesting that its mechanism of action may involve enhancing the host's immune system rather than altering gut microbiota composition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probiotic improves symptomatic and viral clearance in Covid19 outpatients: a randomized, quadruple-blinded, placebo-controlled trial. Gutiérrez-Castrellón, P., Gandara-Martí, T., Abreu Y Abreu, AT., et al.[2023]

In a study of 120 patients with mild COVID-19, those taking a spore-based Bacillus probiotic showed a significantly shorter time to symptom resolution (6.63 days) compared to those not taking probiotics (8.48 days).

Patients on probiotics also experienced faster fever resolution and reported fewer digestive symptoms, indicating that ongoing probiotic treatment may improve clinical outcomes in mild COVID-19 cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ongoing Treatment with a Spore-Based Probiotic Containing Five Strains of Bacillus Improves Outcomes of Mild COVID-19. Catinean, A., Sida, A., Silvestru, C., et al.[2023]

In a study of 44 moderate/severe COVID-19 inpatients, those who received an oral booster of single-strain probiotic bifidobacteria had a significantly shorter hospital stay (median of 7.6 days) compared to those who did not receive the probiotic.

The probiotic group also showed improved clinical outcomes, including better radiological improvement and lower levels of interleukin-6, with a mortality rate of 5% compared to 25% in the non-probiotic group, suggesting that probiotics may enhance recovery in severe COVID-19 cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral booster probiotic bifidobacteria in SARS-COV-2 patients. Bozkurt, HS., Bilen, Ö.[2022]

The study found that the probiotic Lactobacillus plantarum significantly increased the innate cytokine index in healthy individuals, suggesting it may enhance immune responses against COVID-19, with a mean fold change of 17-fold (P=0.0138).

In contrast, another probiotic, Bifidobacterium longum, did not show a significant effect on the innate cytokine index, indicating that not all probiotics have the same immunomodulatory potential against COVID-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lactobacillus plantarum induces innate cytokine responses that potentially provide a protective benefit against COVID-19: A single-arm, double-blind, prospective trial combined with an in vitro cytokine response assay. Kageyama, Y., Nishizaki, Y., Aida, K., et al.[2021]

In a study involving 200 nursing home residents over 60 years old, the probiotic Loigolactobacillus coryniformis K8 did not show a significant difference in overall antibody levels compared to a placebo after COVID-19 vaccination.

However, among those who contracted COVID-19, participants taking K8 had significantly higher IgG antibody levels, suggesting that K8 may enhance the immune response in elderly individuals, particularly in those over 85 years old.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Loigolactobacillus coryniformis K8 CECT 5711 on the Immune Response of Elderly Subjects to COVID-19 Vaccination: A Randomized Controlled Trial. Fernández-Ferreiro, A., Formigo-Couceiro, FJ., Veiga-Gutierrez, R., et al.[2022]

In a study of 35 cancer patients receiving home enteral nutrition, Lactobacillus plantarum 299v (Lp299v) significantly increased serum albumin levels compared to a placebo, indicating potential benefits for nutritional status.

Lp299v also reduced gastrointestinal symptoms like vomiting and flatulence after 4 weeks, suggesting it may help alleviate discomfort associated with enteral nutrition, although it did not significantly improve overall quality of life compared to the placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of 4 weeks of Lactobacillus plantarum 299v supplementation on nutritional status, enteral nutrition tolerance, and quality of life in cancer patients receiving home enteral nutrition - a double-blind, randomized, and placebo-controlled trial. Kaźmierczak-Siedlecka, K., Folwarski, M., Ruszkowski, J., et al.[2021]

Lactobacillus plantarum 299v has been shown to improve gut health by increasing anti-inflammatory cytokines, which can enhance cancer treatment efficacy and reduce gastrointestinal side effects.

This probiotic also benefits patients with irritable bowel syndrome (IBS) by normalizing stool and alleviating abdominal pain, and it helps prevent Clostridium difficile-associated diarrhea in those undergoing antibiotic treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of Lactobacillus plantarum 299v in supporting treatment of selected diseases. Kaźmierczak-Siedlecka, K., Daca, A., Folwarski, M., et al.[2021]

Lactiplantibacillus plantarum 299v (L. plantarum 299v) is a well-researched probiotic strain with over 170 publications, including more than 60 clinical studies, demonstrating its safety and efficacy in improving gastrointestinal health, particularly in reducing symptoms of irritable bowel syndrome (IBS).

This strain not only enhances iron absorption and status but also survives the harsh conditions of the gastrointestinal tract, making it suitable for various food applications and dietary supplements, with a stable shelf-life in freeze-dried formats.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lactiplantibacillus plantarum 299v (LP299V®): three decades of research. Nordström, EA., Teixeira, C., Montelius, C., et al.[2021]

In a study using a rat model of colitis, Lactobacillus plantarum species 299 (LP299) did not improve the severity of colitis or gut permeability compared to untreated controls, indicating it may not be effective in this context.

The experiment involved 48 rats with induced colitis and assessed outcomes like colon macroscopic scoring and gut permeability, but LP299 treatment did not show any beneficial effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probiotic therapy fails to improve gut permeability in a hapten model of colitis. Kennedy, RJ., Hoper, M., Deodhar, K., et al.[2019]

In a study of 3533 hospitalized patients, the routine use of the probiotic Lactobacillus plantarum 299v (LP299v) significantly reduced the incidence of Clostridium difficile infections (CDI) from 1.21% to 0.11% after its implementation as a preventive measure during antibiotic treatment.

The findings suggest that LP299v may be an effective prophylactic option for preventing CDI in high-risk patients receiving antibiotics, particularly in nephrology and transplantation settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Lactobacillus plantarum 299v on the Incidence of Clostridium difficile Infection in High Risk Patients Treated with Antibiotics. Kujawa-Szewieczek, A., Adamczak, M., Kwiecień, K., et al.[2020]

Immunomodulatory strains of Lactiplantibacillus plantarum, particularly MPL16, have been shown to enhance the immune response in human respiratory cells and increase resistance to SARS-CoV-2 infection, indicating potential therapeutic benefits against COVID-19.

This study is the first to demonstrate that specific immunobiotic lactobacilli can positively influence the replication of SARS-CoV-2, suggesting a new avenue for research into probiotics as a preventive or therapeutic strategy for COVID-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunobiotic Lactobacilli Improve Resistance of Respiratory Epithelial Cells to SARS-CoV-2 Infection. Islam, MA., Albarracin, L., Tomokiyo, M., et al.[2021]

The probiotic Lactobacillus plantarum GUANKE (LPG) can enhance immune responses to SARS-CoV-2 vaccines, promoting the production of neutralizing antibodies even 6 months post-vaccination.

Administering LPG immediately after vaccination significantly boosts antibody levels and maintains T-cell responses in both the lungs and spleen, suggesting it could be an effective strategy to prolong vaccine-induced immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Boosting Vaccine-Elicited Respiratory Mucosal and Systemic COVID-19 Immunity in Mice With the Oral Lactobacillus plantarum. Xu, J., Ren, Z., Cao, K., et al.[2022]

The probiotic strain Lacticaseibacillus paracasei DG has shown significant potential in enhancing antiviral immunity and inhibiting SARS-CoV-2 infection in laboratory studies using intestinal epithelial cells.

L. paracasei DG not only directly inhibits SARS-CoV-2 but also boosts the antiviral effects of lactoferrin, suggesting it could be an effective preventive measure against COVID-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lacticaseibacillus paracasei DG enhances the lactoferrin anti-SARS-CoV-2 response in Caco-2 cells. Salaris, C., Scarpa, M., Elli, M., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Probiotic improves symptomatic and viral clearance in Covid19 outpatients: a randomized, quadruple-blinded, placebo-controlled trial. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Ongoing Treatment with a Spore-Based Probiotic Containing Five Strains of Bacillus Improves Outcomes of Mild COVID-19. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Oral booster probiotic bifidobacteria in SARS-COV-2 patients. [2022]

4. Greece pubmed.ncbi.nlm.nih.gov

Lactobacillus plantarum induces innate cytokine responses that potentially provide a protective benefit against COVID-19: A single-arm, double-blind, prospective trial combined with an in vitro cytokine response assay. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of Loigolactobacillus coryniformis K8 CECT 5711 on the Immune Response of Elderly Subjects to COVID-19 Vaccination: A Randomized Controlled Trial. [2022]

6. Italy pubmed.ncbi.nlm.nih.gov

Effects of 4 weeks of Lactobacillus plantarum 299v supplementation on nutritional status, enteral nutrition tolerance, and quality of life in cancer patients receiving home enteral nutrition - a double-blind, randomized, and placebo-controlled trial. [2021]

7. Poland pubmed.ncbi.nlm.nih.gov

The role of Lactobacillus plantarum 299v in supporting treatment of selected diseases. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Lactiplantibacillus plantarum 299v (LP299V®): three decades of research. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Probiotic therapy fails to improve gut permeability in a hapten model of colitis. [2019]

10. Switzerland pubmed.ncbi.nlm.nih.gov

The Effect of Lactobacillus plantarum 299v on the Incidence of Clostridium difficile Infection in High Risk Patients Treated with Antibiotics. [2020]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Immunobiotic Lactobacilli Improve Resistance of Respiratory Epithelial Cells to SARS-CoV-2 Infection. [2021]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Boosting Vaccine-Elicited Respiratory Mucosal and Systemic COVID-19 Immunity in Mice With the Oral Lactobacillus plantarum. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

Lacticaseibacillus paracasei DG enhances the lactoferrin anti-SARS-CoV-2 response in Caco-2 cells. [2021]