Xylitol for C. Difficile

Overseen By Jessica Allegretti, MD MPH

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Brigham and Women's Hospital

Must not be taking: Antibiotics

Disqualifiers: Previous colon surgery, Allergy to xylitol, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 10

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of xylitol (a sugar alcohol) in reducing C. difficile, a harmful gut bacteria, in people with Inflammatory Bowel Disease (IBD). Researchers aim to test different xylitol doses to determine the optimal amount for treatment. The trial includes two groups: one where participants are observed without intervention and another where they receive varying doses of xylitol. People with IBD who have mild or inactive symptoms and are visiting their doctor for a colonoscopy or clinic appointment might be suitable candidates. As an Early Phase 1 trial, this research focuses on understanding how xylitol works in people, offering participants a chance to contribute to groundbreaking treatment development.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those who are on chronic antibiotics.

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

Research shows that xylitol is usually safe for people and often serves as a sugar substitute. This trial remains in the early stages, so the researchers are still collecting safety information. However, since xylitol is commonly found in foods, most people seem to tolerate it well. The sources have not reported specific negative effects, suggesting it is promising in terms of safety. Ongoing studies will help confirm these early findings. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using xylitol to treat C. difficile because it offers a unique approach compared to current antibiotics. Most treatments for C. difficile aim to kill the bacteria, but xylitol may work differently by disrupting the bacteria's ability to colonize the gut. This sugar alcohol has been used safely in other contexts, like dental care, which gives researchers hope for its safety profile. Additionally, xylitol's potential to prevent bacterial adhesion could offer a new way to manage infections without contributing to antibiotic resistance.

What evidence suggests that xylitol might be an effective treatment for C. difficile?

Research shows that xylitol can prevent C. difficile bacteria from adhering to intestinal cells, potentially preventing infections. In animal studies, xylitol has shown promise in controlling C. difficile growth. Additionally, one study found that xylitol works well with probiotic bacteria to inhibit C. difficile spores from growing and causing infection. These findings suggest that xylitol could help reduce C. difficile infections, especially in individuals with conditions like Inflammatory Bowel Disease (IBD). This trial includes a Dose Finding Cohort where participants will receive one of five consecutively increasing doses of xylitol to further investigate its effectiveness. Meanwhile, an Observational Cohort will assess rates of spontaneous decolonization. While these early results are promising, more research is needed to confirm xylitol's effectiveness in humans. ^{2 3 4 6 7}

Who Is on the Research Team?

Jessica Allegretti, MD MPH

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Inflammatory Bowel Disease (IBD) who are coming in for a colonoscopy or clinic visit. They should have inactive or mild IBD, as shown by specific low disease scores. People can't join if they use antibiotics often, had certain gut surgeries, can't swallow pills, or are allergic to xylitol.

Inclusion Criteria

Signed informed consent

I am scheduled for an outpatient colonoscopy or clinic visit.

My inflammatory bowel disease is mild or inactive.

Exclusion Criteria

I regularly take antibiotics for a long-term condition.

I am unable to give my consent.

I have had surgery on my colon, such as a colectomy, ostomy, or J-pouch.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants receive daily doses of xylitol for 7 days in one of five dosing groups

1 week

1 visit (in-person), weekly phone calls

Follow-up

Participants are monitored for safety, efficacy, and clinical outcomes, including C. difficile decolonization and IBD activity

26 weeks

Assessments at Week 8 and Week 26

What Are the Treatments Tested in This Trial?

Interventions

• Xylitol

Trial Overview

The trial is testing the safety and effectiveness of xylitol, a sugar alcohol used as a sweetener, to remove C. difficile bacteria from the gut in people with IBD. It's an early-stage study where participants will take increasing doses of xylitol orally.

How Is the Trial Designed?

Group I: Dose Finding Cohort Experimental Treatment 1 Intervention

One of five consecutively increasing dosing groups of xylitol

Group II: Observational Cohort Active Control 1 Intervention

Participants will be assessed for rates of spontaneous decolonization, stool sample testing and IBD scoring.

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Published Research Related to This Trial

C. difficile infections are on the rise in developed countries due to factors like antibiotic overuse and the emergence of new strains, highlighting the urgent need for better treatment options.

The review discusses both current treatments and promising new agents in development, focusing on antibiotics that may offer improved efficacy, selectivity, and reduced side effects compared to existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress in the discovery of treatments for C. difficile infection: A clinical and medicinal chemistry review. Tsutsumi, LS., Owusu, YB., Hurdle, JG., et al.[2021]

In a pooled analysis of the MODIFY I and II trials involving patients with recurrent Clostridium difficile infection (rCDI), bezlotoxumab treatment was associated with a reduction in cumulative inpatient-days, averaging 12.1 days compared to 14.1 days for the placebo group over an 84-day follow-up period.

The reduction in inpatient-days was more pronounced in patients with multiple risk factors for rCDI, indicating that bezlotoxumab may significantly decrease healthcare resource use for those at higher risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bezlotoxumab Is Associated With a Reduction in Cumulative Inpatient-Days: Analysis of the Hospitalization Data From the MODIFY I and II Clinical Trials. Basu, A., Prabhu, VS., Dorr, MB., et al.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6335148/

Probiotics for Prevention of Clostridium difficile Infection

Probiotic use may reduce incident CDI in high risk populations by as much as 50%, though prior clinical trials have yielded conflicting results.

2.

sciencedirect.com

sciencedirect.com/science/article/pii/S2590097825000023

Potential therapeutic solution for Clostridioides difficile ...

A combination of probiotic and prebiotic treatments has been found effective in reducing C. difficile growth in vivo [101]. Probiotics and prebiotics perform ...

3.

withpower.com

withpower.com/trial/xylitol-for-c-difficile-c38a2

Xylitol for C. Difficile · Info for Participants

Research shows that xylitol can reduce the ability of C. difficile bacteria to stick to intestinal cells, which might help prevent infections. In animal studies ...

4.

ctv.veeva.com

ctv.veeva.com/study/xylitol-use-for-decolonization-of-c-difficile-in-patients-with-ibd

Xylitol Use for Decolonization of C. Difficile in Patients With IBD

This randomized placebo-controlled dose-finding trial will assess the safety and efficacy of xylitol as an oral therapeutic for decolonization ...

5.

researchgate.net

researchgate.net/publication/316590063_A_combination_of_the_probiotic_and_prebiotic_product_can_prevent_the_germination_of_Clostridium_difficile_spores_and_infection

A combination of the probiotic and prebiotic product can ...

... The synergistic effect between xylitol and probiotic bacteria was demonstrated in a study using Clostridioides difficile, a microorganism ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40636622/

Prevention of Clostridium Difficile Infection Among ...

Conclusions: This RCT shall document the effect of the Torani-xylitol mixture on CDI prevention and CD colonization among hospitalized elderly ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8611198/

Frontiers in antibiotic alternatives for Clostridioides difficile ...

Clostridioides difficile (C. difficile) is a gram-positive, anaerobic spore-forming bacterium and a major cause of antibiotic-associated diarrhea.