Probiotics for Long COVID

(PURE-LC Trial)

Overseen By Michelle Santangelo, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Rush University Medical Center

Must not be taking: Immunosuppressants, Probiotics

Disqualifiers: Pregnancy, Breastfeeding, Immune conditions, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

180 Participants Needed

Trial Summary

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 immunosuppressants or regularly taking probiotics.

What data supports the effectiveness of the treatment Probiotic Agent for Long COVID?

Research suggests that probiotics may help improve outcomes for COVID-19 patients by reducing symptoms like fever and digestive issues, and potentially shortening hospital stays. While these studies focus on COVID-19, they indicate that probiotics could support recovery by enhancing gut health and immune response, which might be beneficial for Long COVID as well. ^{1 2 3 4 5}

Is the probiotic treatment safe for humans?

Research on probiotics for COVID-19 patients shows they are generally safe, with no significant side effects reported. In one study, healthcare workers taking a specific probiotic reported fewer side effects from the COVID-19 vaccine, like less arm pain. ^{4 6 7 8 9}

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

The probiotic treatment for Long COVID is unique because it focuses on improving gut health and the microbiome, which can influence immune responses and reduce inflammation. Unlike standard treatments that may target specific symptoms, probiotics aim to restore balance in the gut, potentially alleviating gastrointestinal symptoms and supporting overall recovery. ^{3 5 10 11 12}

What is the purpose of this trial?

The goal of this clinical trial is to learn if probiotics can improve symptoms and quality of life in participants with Long COVID. The main questions it aims to answer are: 1. Do probiotics reduce the number and severity of symptoms in those with Long COVID? 2. Do probiotics improve physical and mental health quality of life in those with Long COVID? 3. Do probiotics improve return to work and daily activities in those with Long COVID? Researchers will compare probiotics to a placebo (a look-alike substance that contains no probiotics) to see if probiotics works to treat Long COVID. Participants will take the study medication (placebo or probiotic) for 4 months. They will then cross-over (take the other medication) for an additional 4 months. Participants will complete a survey at baseline, 4 months, and 8 months.

Eligibility Criteria

This trial is for individuals experiencing lingering symptoms after COVID-19, known as Long COVID. Participants should have ongoing issues but no current infection. The study excludes those with immune system disorders, on certain medications, or who are pregnant.

Inclusion Criteria

I am over 18 and have long-lasting symptoms from COVID.

Exclusion Criteria

I do not have symptoms of Long COVID anymore.

Are unable to take the study medication daily

Are currently pregnant or planning to become pregnant over the course of the study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1

Participants receive either probiotics or placebo for 4 months

16 weeks

1 visit (in-person) at baseline, 1 survey at 4 months

Treatment Phase 2

Participants cross-over to the other treatment (probiotics or placebo) for an additional 4 months

16 weeks

1 survey at 8 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Probiotic Agent

Trial Overview The study tests if probiotics can alleviate Long COVID symptoms and improve life quality compared to a placebo. It's a crossover trial where participants switch between the probiotic and placebo every four months and report their progress.

Participant Groups

Group I: Probiotic Arm Active Control 1 Intervention

Probiotic pill taken once daily

Group II: Placebo Arm Placebo Group 1 Intervention

Identical placebo pill taken once daily

Who Is Running the Clinical Trial?

Rush University Medical Center

Lead Sponsor

Trials

448

Recruited

247,000+

Findings from Research

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]

A study involving 200 hospitalized COVID-19 patients found that a multi-strain probiotic did not significantly affect overall mortality or major health outcomes, such as the need for intensive care or mechanical ventilation.

However, the probiotic was effective in reducing the duration of diarrhea associated with COVID-19 and preventing hospital-acquired diarrhea in patients receiving a single antibiotic, indicating its potential benefit in managing gastrointestinal symptoms during COVID-19 treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of a Probiotic Consisting of Lacticaseibacillus rhamnosus PDV 1705, Bifidobacterium bifidum PDV 0903, Bifidobacterium longum subsp. infantis PDV 1911, and Bifidobacterium longum subsp. longum PDV 2301 in the Treatment of Hospitalized Patients with COVID-19: a Randomized Controlled Trial. Ivashkin, V., Fomin, V., Moiseev, S., 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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Probiotics use is associated with improved clinical outcomes among hospitalized patients with COVID-19. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Potential beneficial role of probiotics on the outcome of COVID-19 patients: An evolving perspective. [2021]

3. 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]

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

Efficacy of a Probiotic Consisting of Lacticaseibacillus rhamnosus PDV 1705, Bifidobacterium bifidum PDV 0903, Bifidobacterium longum subsp. infantis PDV 1911, and Bifidobacterium longum subsp. longum PDV 2301 in the Treatment of Hospitalized Patients with COVID-19: a Randomized Controlled Trial. [2023]

5. England pubmed.ncbi.nlm.nih.gov

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

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

Probiotics for treating novel coronavirus with diarrhea: A protocol for systematic review and meta analysis. [2022]

7. China pubmed.ncbi.nlm.nih.gov

The efficacy of probiotics in patients with severe COVID-19. [2022]

8. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Efficacy of Saccharomyces boulardii CNCM I-745 probiotic drug in the prevention and treatment of diarrhea in hospitalized patients with new coronavirus infection COVID-19]. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Evaluation of the effect of Loigolactobacillus coryniformis K8 CECT 5711 consumption in health care workers exposed to COVID-19. [2022]

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

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

11. Netherlands pubmed.ncbi.nlm.nih.gov

Microbiome and intestinal pathophysiology in post-acute sequelae of COVID-19. [2023]

12. 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]