Pilot Trial of Xylitol for C. Difficile De-Colonization in Patients With Inflammatory Bowel Disease

This 3+3 dose escalation pilot trial will assess the safety and efficacy of xylitol as an oral therapeutic for decolonization of C. difficile in the Inflammatory Bowel Disease (IBD) patient population.

Study Overview

• Status: Not yet recruiting
• Conditions: Inflammatory Bowel Disease (IBD); Clostridioides Difficile Infection
• Intervention / Treatment: Drug: Xylitol

Detailed Description

Participants with confirmed IBD diagnosis who are scheduled for an outpatient colonoscopy for any reason at Brigham and Women's Hospital will be eligible for enrollment. Participants will be screened for C. difficile colonization via colonic wash sampling during colonoscopy. Participants may only have inactive or mild IBD at the time of the colonoscopy to be eligible.

Eligible participants will be initially enrolled in the observational cohort until there are 39 subjects enrolled. Participants in the observational cohort will be assessed at Week 1, 4 and 8, following confirmation of colonization. Participants will only be assessed for stool sample testing, IBD scoring and occurrence of CDI.

The subsequent participants who meet eligibility criteria will be enrolled into one of five consecutively increasing dosing groups of xylitol. The dose A treatment arm will receive a daily dose of 1 gram of xylitol for 7 days. The dose B treatment arm will receive a daily dose of 2 grams of xylitol for 7 days. The dose C treatment group will receive a daily dose of 5 grams of xylitol for 7 days. The dose D treatment group will receive a daily dose of 7 grams of xylitol for 7 days. The dose E treatment group will receive a daily dose of 9 grams of xylitol for 7 days. Participants will end dosing at day 7 but monitoring will continue through to week 8.

Participants in the will be assessed through week 8 for the primary outcome, determining the maximum tolerated dosage of xylitol. C. difficile decolonization will be assessed through week 8. Participants will also receive weekly phone call for assessment of symptoms and tolerability through week 8. In addition, secondary efficacy outcomes including IBD disease activity and development of CDI will be evaluated at week 8, and week 26. Participants will also be followed through week 26 for long-term safety, efficacy, and clinical outcomes. Disease activity and symptoms will be recorded from informed consent through the week 26 trial visit.

The primary outcome, determining the maximum tolerated dose of xylitol at week 8 will be confirmed via adverse event reporting. Additional C. difficile testing will be done at week 26.

The study will prospectively enroll between 15 and 30 adult participants at a single center. Participants that experience intolerable adverse events will be withdrawn from the study and will be considered treatment failures.

• Study Type: Interventional
• Enrollment (Estimated): 69
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Heidy Cabral; Phone Number: 617-525-7322; Email: hjcabral@bwh.harvard.edu
• Study Contact Backup: Name: Jessica Allegretti, MD MPH; Phone Number: 617-732-6389

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
      • Contact: Heidy Cabral; Phone Number: 617-525-7322; Email: hjcabral@bwh.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed informed consent.
2. Male or female ≥ 18 years of age
3. IBD diagnosis (CD, UC or indeterminant Colitis will be permitted)
4. Inactive or mild IBD (HBI score ≤ 4; Partial Mayo score ≤ 4)
5. Presenting for outpatient colonoscopy or clinic appointment

Exclusion Criteria:

1. Unable to provide consent.
2. Patients with previous colectomy, ostomy, J-pouch, or previous colon surgery (excluding appendectomy)
3. Unable to complete study procedures.
4. Chronic use of antibiotics.
5. Inability or unwillingness to swallow capsules.
6. Allergy to xylitol.
7. Currently pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Finding Cohort; One of five consecutively increasing dosing groups of xylitol	Drug: Xylitol; Xylitol is a sugar alcohol and considered a GRAS substance by the FDA. Patients will be consecutively enrolled into one of five dosing including 1g, 2g, 5g, 7g and 9g.
No Intervention: Observational Cohort; Participants will be assessed for rates of spontaneous decolonization, stool sample testing and IBD scoring.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
C. Diff Decolonization	Proportion of patients decolonized of C. difficile at Week 8	8 weeks
Safety and Efficacy of Xylitol	Incidence of Treatment Emergent Adverse Events (TEAEs) through Week 8	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomass of C. Difficile	Change in biomass of C. difficile in patients at Week 8	8 weeks
Effect of C. difficile decolonization on Inflammatory Bowel Disease (IBD) clinical outcomes	Change in IBD clinical score at Week 8 and Week 26. IBD clinical scores are used to assess IBD patient symptoms. The assessments are separated between scores for Ulcerative Colitis (UC) and Crohn's Disease (CD). The Harvey Bradshaw Index (HBI) is a clinical assessment for IBD patients with Crohn's disease while Partial Mayo Score is a clinical assessment for Ulcerative Colitis. The scores will be collected at study visit in form of a survey. The HBI score can vary but a score above 8 or 9 is considered severe disease activity. The Partial Mayo Score can range from 0 to 9 and a score above 7 is considered severe disease activity. A decrease in score from baseline to follow-up timepoints is indicative of improved IBD patient symptoms.	26 weeks
C. Difficile infection surveillance	Incidence of patients developing C. Difficile Infection through Week 26	26 weeks

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Investigators: Principal Investigator: Jessica Allegretti, MD MPH, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): September 1, 2031

Study Registration Dates

• First Submitted: January 23, 2025
• First Submitted That Met QC Criteria: January 23, 2025
• First Posted (Actual): January 29, 2025

Study Record Updates

• Last Update Posted (Actual): December 16, 2025
• Last Update Submitted That Met QC Criteria: December 8, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: IBD; Decolonization; C. Difficile
• Additional Relevant MeSH Terms: Intestinal Diseases; Infections; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Clostridium Infections; Inflammatory Bowel Diseases; Organic Chemicals; Carbohydrates; Alcohols; Sugar Alcohols; Xylitol
• Other Study ID Numbers: 2025P000210

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes