Clinical trial NCT06799039: Pilot Trial of Xylitol for C. Difficile De-Colonization in Patients with Inflammatory Bowel Disease
Official title: Pilot Trial of Xylitol for C. Difficile De-Colonization in Patients with Inflammatory Bowel Disease
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: EARLY_PHASE1
Conditions: Inflammatory Bowel Disease (IBD)
Clostridioides Difficile Infection
Keywords: C. Difficile
Decolonization
IBD
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2025-01-29
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Dose Finding
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: Participants with confirmed IBD diagnosis who are scheduled for an outpatient colonoscopy for any reason at Brigham and Women's Hospital or clinic appointment at the Crohn's and Colitis Center will be eligible for enrollment. Participants will be screened for C. difficile colonization via colonic wash sampling during colonoscopy or whole stool at or following clinic appointment. Participants may only have inactive or mild IBD at the time of the colonoscopy or clinic visit to be eligible.

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 who meet eligibility criteria but do not want to participate in the trial will also be eligible to enroll in an observational cohort. Participants in the observational cohort will be assessed at Week 1, 4 and 8, following confirmation of colonization. Participants will be assessed for rates of spontaneous decolonization, stool sample testing and IBD scoring.

Participants in the treatment cohort will be assessed thorough 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety and Efficacy of Xylitol
timeFrame: 8 weeks
measure: C. Diff Decolonization
timeFrame: 8 weeks
Secondary outcomes:
measure: Biomass of C. Difficile
timeFrame: 8 weeks
measure: Effect of C. difficile decolonization on Inflammatory Bowel Disease (IBD) clinical outcomes
timeFrame: 26 weeks
measure: C. Difficile infection surveillance
timeFrame: 26 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Jessica Allegretti, MD MPH
role: PRINCIPAL_INVESTIGATOR
References: