Probiotics for Healthy Subjects

Overseen By Monique Torres

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Mayo Clinic

Must not be taking: Antibacterials, NSAIDs, Steroids, Antifungals

Disqualifiers: Gastrointestinal disease, Diabetes, Hypertension, Immune deficiency, others

Compensation: Varies

Number of Visits: 1

Duration: 2 weeks

56 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether the probiotic S. boulardii CNCM I-745 can improve gut health by controlling what passes through the gut wall. Participants will take either the probiotic or a placebo while also receiving Indomethacin, a common medication. The trial seeks healthy individuals with regular bowel movements and no history of serious gut issues or recent use of probiotics or certain medications. This offers an opportunity to explore how probiotics might help maintain a healthy digestive system. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, allowing participants to contribute to groundbreaking insights into gut health.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop all current medications, but certain medications are restricted. You cannot have taken oral or systemic antibacterial therapy, NSAIDs, proton pump inhibitors, steroids, or medications affecting gastrointestinal transit or permeability within specific timeframes before the study. Check with the study team for details on your specific medications.

Is there any evidence suggesting that S. boulardii CNCM I-745 is likely to be safe for humans?

Research has shown that S. boulardii CNCM I-745 is generally safe for use. Studies have found it helps treat symptoms like diarrhea and is safe to take. Trials conducted in China found this probiotic to be safe, with participants rarely experiencing serious side effects. This suggests that most people can use S. boulardii CNCM I-745 without major problems. However, since this information is based on other studies, individual experiences may vary. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

S. boulardii CNCM I-745 is unique because it involves a probiotic approach, which is different from typical anti-inflammatory medications used for similar conditions. Most treatments rely on drugs like NSAIDs to manage symptoms, but this probiotic works by potentially restoring gut health and balance. Researchers are excited because it could offer a natural alternative with fewer side effects, targeting the microbiome to support overall digestive health. This innovative approach may provide benefits more quickly than traditional methods.

What evidence suggests that S. boulardii CNCM I-745 might be an effective treatment for impaired intestinal permeability?

Research has shown that S. boulardii CNCM I-745 can help with gut problems. In several studies, this probiotic reduced diarrhea symptoms by up to 24 hours and helped prevent and treat antibiotic-associated diarrhea. In this trial, participants in the S. boulardii CNCM I-745 group will receive this probiotic to evaluate its effects on gut health. These findings suggest that S. boulardii CNCM I-745 might improve gut health by supporting the gut lining. Although direct information on its impact on the gut barrier is limited, these results are promising for gut-related issues. ^{1 2 4 6 7}

Who Is on the Research Team?

Michael Camilleri, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

Healthy adults with a BMI of 18-35 kg/m^2 and weight over 50 kg can join. Women who can get pregnant must test negative for pregnancy and agree to use contraception. Participants should have regular bowel movements, not be in another trial recently, or have taken certain drugs that affect the gut.

Inclusion Criteria

Able to comply with study requirements and to provide signed informed consent.

Has signed the informed consent form before beginning any study procedure.

For women of childbearing potential: A negative urine pregnancy test immediately prior to starting the study treatment; Agreement to comply with approved methods of contraception during the whole study: unless they meet the criteria of post-menopausal; i.e., 12 months of spontaneous amenorrhea, women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner, should use one or more of the following acceptable methods of contraception that should be maintained throughout the study: Surgical sterilization; Hormonal contraception (implantable, patch, oral, intra-muscular); Intra-uterine device; Double barrier method (diaphragm plus condom); At the discretion of the investigator, total abstinence is acceptable in cases where age, career, lifestyle, or sexual orientation of the patient ensures compliance.

Exclusion Criteria

Patients enrolled in another clinical trial within the past 30 days

Patients not able to fill in the study questionnaires

History of hypersensitivity to the study treatments (active substance or excipients), brewer's or baker's yeast

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Treatment

Participants receive Indomethacin from day 2 to day 7 and either S. boulardii CNCM I-745 or placebo from day 1 to day 14

2 weeks

Multiple visits for assessments and sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments on day 20 for placebo group

1 week

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• S. boulardii CNCM I-745

Trial Overview

The study tests if S. boulardii CNCM I-745 improves intestinal barrier function compared to placebo in healthy people. It also looks at how indomethacin affects this process by possibly impairing the gut lining's control of material passage into the body.

How Is the Trial Designed?

Group I: S. boulardii CNCM I-745 Group Experimental Treatment 2 Interventions

Subjects will receive Indomethacin from day 2 to day 7 and S. boulardii CNCM I-745 from day 1 to day 14

Group II: Placebo Group Placebo Group 2 Interventions

Subjects will receive Indomethacin from day 2 to day 7 and Placebo from day 1 to day 14

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

In a study involving 52 colorectal cancer patients, those who consumed a probiotic mixture for six months showed a significant reduction in several pro-inflammatory cytokines, indicating a potential anti-inflammatory effect of probiotics post-surgery.

The probiotics were found to be safe for consumption after surgery, with no surgical infections reported, suggesting they could be a beneficial addition to the recovery process for colorectal cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized double-blind placebo-controlled trial of probiotics in post-surgical colorectal cancer. Zaharuddin, L., Mokhtar, NM., Muhammad Nawawi, KN., et al.[2020]

In a study of 154 patients with Crohn's disease in clinical remission, taking the probiotic Saccharomyces boulardii for over 6 months significantly improved the Crohn's Disease Activity Index (CDAI), body mass index (BMI), hemoglobin levels, and total cholesterol without any safety concerns.

The study found that while S. boulardii led to meaningful improvements in several health markers, other measures like fecal calprotectin and CRP did not show significant changes, indicating that the probiotic may specifically enhance certain aspects of health in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in the Crohn's Disease Activity Index and Safety of Administering Saccharomyces Boulardii in Patients with Crohn's Disease in Clinical Remission: A Single Hospital-based Retrospective Cohort Study. Oh, GM., Moon, W., Seo, KI., et al.[2021]

Saccharomyces boulardii CNCM I-745 is a unique probiotic yeast that offers several mechanisms of action, including adhesion to harmful microorganisms, toxin elimination, and anti-inflammatory effects on the gut, making it effective in treating various gastrointestinal diseases.

This probiotic is particularly advantageous during antibiotic therapy because it is resistant to antibiotics, reducing the risk of promoting antimicrobial resistance, and is generally considered safe despite rare reports of fungemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Saccharomyces boulardii CNCM I-745: A Non-bacterial Microorganism Used as Probiotic Agent in Supporting Treatment of Selected Diseases. Kaźmierczak-Siedlecka, K., Ruszkowski, J., Fic, M., et al.[2021]

Fecal microbial transplantation is strongly supported as an effective treatment for recurrent Clostridium difficile infections based on evidence from randomized clinical trials.

Moderate evidence suggests that certain probiotics, like Lactobacillus and Bifidobacterium, can help prevent antibiotic-associated diarrhea and serve as adjunct therapy for Helicobacter pylori treatment, but overall, many studies are small and of low quality, indicating a need for further research before routine recommendations can be made.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probiotics in Gastroenterology: How Pro Is the Evidence in Adults? Koretz, RL.[2019]

The probiotic yeast Saccharomyces boulardii CNCM I-745 effectively helps restore a healthy gut microbiome during dysbiosis, such as diarrhea, by increasing beneficial bacteria and suppressing harmful ones.

S. boulardii has multiple mechanisms of action, including immunological effects and enhancing the growth of beneficial intestinal microbiota, making it a promising option for preventing and treating diarrhea, especially in at-risk populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Saccharomyces boulardii CNCM I-745 supports regeneration of the intestinal microbiota after diarrheic dysbiosis - a review. Moré, MI., Swidsinski, A.[2020]

The probiotic Saccharomyces boulardii CNCM I-745 is effective in preventing and treating various types of diarrhea, including antibiotic-associated and Clostridium difficile-associated diarrhea, by enhancing the gut-associated immune system.

S. boulardii works through multiple mechanisms, including directly affecting pathogens and their toxins, modulating immune responses, and preserving the integrity of the intestinal lining, which helps reduce fluid leakage and inflammation during diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of Saccharomyces boulardii CNCM I-745on the gut-associated immune system. Stier, H., Bischoff, SC.[2022]

In a study involving female C57BL/6 mice, supplementation with Saccharomyces boulardii significantly reduced weight loss and colon inflammation, while improving intestinal barrier integrity during experimental colitis.

S. boulardii reshaped the gut microbiome by increasing beneficial bacteria and decreasing harmful ones, which was linked to improved metabolic profiles and reduced inflammation, suggesting its potential as a therapeutic option for inflammatory bowel diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Saccharomyces boulardii protects against murine experimental colitis by reshaping the gut microbiome and its metabolic profile. Gao, H., Li, Y., Xu, J., et al.[2023]

Saccharomyces boulardii is an effective probiotic for children, particularly in treating acute gastroenteritis and preventing antibiotic-associated diarrhea, supported by double-blind placebo-controlled studies.

The mechanisms of action include inhibiting bacterial toxins, reducing inflammation, and stimulating the intestinal mucosa, which highlights its potential for broader therapeutic uses beyond current indications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Saccharomyces boulardii in childhood. Vandenplas, Y., Brunser, O., Szajewska, H.[2021]

Saccharomyces boulardii CNCM I-745 is an effective probiotic that significantly reduces the risk of antibiotic-associated diarrhea (AAD) and restores gut microbiota diversity, making it a valuable option for patients undergoing antibiotic treatment.

In children with pediatric acute gastroenteritis (PAGE), S. boulardii CNCM I-745 outperformed other probiotics, such as Lactobacillus rhamnosus GG, in reducing diarrhea duration and hospital stay, and is considered safe for both children and adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unique Properties of Yeast Probiotic Saccharomyces boulardii CNCM I-745: A Narrative Review. Gopalan, S., Ganapathy, S., Mitra, M., et al.[2023]

The probiotic yeast strain Unique 28 (Saccharomyces boulardii) was found to be safe for human consumption, as it showed no signs of toxicity in rats even at high doses (up to 6,500 mg/kg for acute toxicity and 1,300 mg/kg for sub-acute toxicity).

In a 14-week sub-acute toxicity study, Unique 28 did not produce any adverse effects, indicating its potential for safe use in treating conditions like diarrhea and inflammatory bowel disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety assessment studies of probiotic Saccharomyces boulardii strain Unique 28 in Sprague-Dawley rats. Sudha, MR.[2013]

Saccharomyces boulardii CNCM I-745 is effective in preventing antibiotic-associated diarrhea and works by targeting harmful microorganisms and supporting the intestinal mucosa, making it a valuable probiotic.

This yeast does not disrupt the microbiota in healthy individuals but can help restore it more quickly in those suffering from antibiotic-related issues or chronic diarrhea, suggesting its potential for broader therapeutic applications in intestinal infections and inflammatory diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diversity of Saccharomyces boulardii CNCM I-745 mechanisms of action against intestinal infections. Czerucka, D., Rampal, P.[2020]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40535538/

Efficacy and safety of Saccharomyces boulardii CNCM I ...

S. boulardii CNCM I-745 was found to significantly reduce the duration of PAGE (SMD=-1.63 days, 95% CI -2.08, -1.18), improve the total ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12174131/

Efficacy and safety of Saccharomyces boulardii CNCM I- ...

Our review found S. boulardii CNCM I-745 significantly reduced the duration of PAGE, significantly improved diarrheal symptoms and had a higher ...

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S2052297520301189

Retrospective analysis of EMR database to assess the ...

boulardii was able to reduce the duration of diarrhoea by approximately 24 hours (–0.99 days; 95% CI –1.40 to –0.58). Saccharomyces boulardii probiotic is not ...

4.

wjgnet.com

wjgnet.com/1007-9327/full/v25/i18/2188.htm

Diversity of Saccharomyces boulardii CNCM I-745 ...

boulardii CNCM I-745 has a preventive effect in diarrhea associated with antibiotics[6,7]; the second study also demonstrated a curative effect.

5.

pghn.org

pghn.org/Synapse/Data/PDFData/1121PGHN/pghn-18-17.pdf

The Efficacy of Saccharomyces boulardii CNCM I-745 in ...

In the control group, diarrhea occurred in 26 cases (28.26%), starting after 4.05±1.11 days, lasting 4.02±0.87 days, and in six cases eradication treatment was.

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07168434

Saccharomyces Boulardii CNCM I-745 in Irritable Bowel ...

To demonstrate the efficacy of Saccharomyces boulardii CNCM I-745 on global and individual Irritable Bowel Syndrome (IBS) symptoms, measured by ...

7.

bpspubs.onlinelibrary.wiley.com

bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.16200

Use of Saccharomyces boulardii CNCM I‐745 as ...

This study examined the protective effects of the probiotic Saccharomyces boulardii CNCM I-745 in a rat model of diclofenac-induced enteropathy.