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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if probiotics can improve symptoms and quality of life for individuals with Long COVID. Participants will take either a daily probiotic pill or a placebo, which resembles the probiotic but contains no active ingredients. The trial suits adults still experiencing Long COVID symptoms and not currently using probiotics. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important findings.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that most people can take probiotics without problems. However, some have experienced side effects such as stomach issues, including diarrhea, nausea, and vomiting. While these side effects are uncommon, they can occur. This clinical trial is in Phase 2, indicating that earlier studies have already demonstrated probiotics to be somewhat safe. The trial aims to gather more information to confirm their safety and effectiveness in treating Long COVID. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Long COVID?

Unlike the standard treatments for Long COVID, which often focus on managing symptoms with medications like antihistamines, steroids, or antivirals, this approach uses a probiotic agent. Researchers are excited about this treatment because probiotics offer a unique mechanism of action by potentially restoring gut microbiota balance, which may play a role in reducing inflammation and improving immune function. This innovative approach could address the root cause of lingering symptoms rather than just alleviating them, offering a new avenue for relief to patients.

What evidence suggests that this treatment might be an effective treatment for Long COVID?

Research has shown that probiotics might help with Long COVID symptoms. They have eased issues like fever, cough, and trouble breathing in people with COVID-19. Probiotics contain beneficial bacteria, such as Lactobacillus and Bifidobacterium, which may help maintain gut and brain balance. This balance could reduce inflammation and aid recovery. Studies have examined how probiotics can shorten the duration of COVID-19 symptoms, suggesting they might also benefit those with Long COVID. While the results are promising, further research is needed to confirm these effects in Long COVID patients. Participants in this trial will receive either a probiotic pill or an identical placebo pill to assess the effectiveness of probiotics in managing Long COVID symptoms. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

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

Are unable to take the study medication daily

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

Have been diagnosed with an immune-compromising condition

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12566607/

The Role of Probiotics and Their Postbiotic Metabolites in Post ... Many of patients who have survived the acute phase of SARS-CoV-2 infection experience long-term symptoms, collectively known as “post-acute COVID-19 syndrome” ( ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2667268524001141

Beneficial effects of probiotics to flatten the curve of COVID- ... We found that probiotics decrease fever, cough, nasal congestion, shortness of breath and diarrhea in patients with corona virus disease.

3. molmed.biomedcentral.com molmed.biomedcentral.com/articles/10.1186/s10020-024-00986-6

Chronic inflammation in post-acute sequelae of COVID-19 ... This review is focused on understanding the risk factors of Long COVID with a special emphasis on the dysregulation of the gut-brain axis.

4. thelancet.com thelancet.com/journals/laninf/article/PIIS1473-3099(23)00735-1/fulltext

Synbiotics in post-acute COVID-19 syndrome—a potential ... There are now several studies showing that probiotics, consisting of beneficial bacteria such as Lactobacillus and Bifidobacterium species, ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04621071

Efficacy of Probiotics in Reducing Duration and Symptoms ... This randomized controlled trial aims to evaluate the efficacy of probiotics to reduce the duration and symptoms of COVID-19 in a symptomatic population tested ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0753332225000496

Subphenotypes of Long COVID and the clinical ... This review provides insights into distinct subphenotypes of Long COVID and identifies microbiota dysbiosis as a common theme and crucial target for future ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06643299?cond=COVID

Study Details | NCT06643299 | Probiotic Use for Recovery ... Placebo produced to be identical in taste and appearance to the probiotic agent, taken once daily for a four-month period. What is the study measuring? Primary ...