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

Study Overview
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Brief Summary
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This is a randomized placebo controlled study to assess the safety and efficacy of xylitol as an oral therapeutic for decolonization of C. difficile in IBD patients. A total of 72 patients who meet eligibility criteria will be randomized 1:1 to either the xylitol or sucralose (placebo) arm. Both arms will receive a dose comprising five capsules BID for four weeks. Microbiome assessment and C. difficile testing will be performed at baseline, week 4, 8, 26, and 52.

Detailed Description
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This randomized placebo-controlled trial will assess the safety and efficacy of xylitol as an oral therapeutic for decolonization of C. difficile in the IBD patient population. Participants with confirmed IBD diagnosis (regardless of disease activity) 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 during colonoscopy for C. difficile colonization via colonic wash sampling. Participants who meet eligibility criteria will be randomized 1:1 to either placebo or xylitol. The treatment arm will receive BID dosing of 7.5 grams via gel capsule for 4 weeks. The placebo arm will receive sucralose at BID dosing of 250 mg via gel capsule for 4 weeks. Participants will end dosing at week 4 but monitoring will continue to week 8. Both participants and study team will be blinded to treatment arm allocation. Participants will be assessed through week 8 for the primary outcome, decolonization. Safety and tolerability outcomes will be assessed through week 8. In addition, secondary efficacy outcomes including IBD disease activity and development of CDI will be evaluated at week 8 and week 52. Participants will also be followed through week 52 for long-term safety, efficacy, and clinical outcomes. Disease activity and symptoms will be recorded from time of informed consent through to the week 52 trial visit. Stool samples for biomarker assessments and C. difficile testing will be collected at scheduled trial visits per Schedule of Assessments. The primary outcome, decolonization of C. Difficile at week 8, will be confirmed via stool sampling. Additional C. difficile testing will be done at week 26 and week 52. The study will prospectively enroll approximately 56 adult participants at a single center. Participants that experience intolerable adverse events will be withdrawn from the study and will be considered treatment failures. Data from these patients will be carried forward from last evaluable assessment.

Official Title
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Xylitol Use for Decolonization of C. Difficile in Patients With Inflammatory Bowel Disease

Conditions
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Inflammatory Bowel Diseases, Clostridioides Difficile Infection

Intervention / Treatment
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* Drug: Xylitol
* Drug: Sucralose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent. Male or female ≥ 18 years of age IBD diagnosis (CD, UC or indeterminant Colitis will be permitted) Presenting for outpatient colonoscopy for any indication Exclusion Criteria: Unable to provide consent Patients with previous colectomy, ostomy, J-pouch, or previous colon surgery (excluding appendectomy) Unable to complete study procedures Chronic use of antibiotics Inability or unwillingness to swallow capsules Allergy to xylitol or sucralose

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Xylitol<br>Patients in this arm will be receiving 7.5g/day of Xylitol over a 4 week period. | Drug: Xylitol<br>* Xylitol is a sugar alcohol and considered a GRAS substance by the FDA. Xylitol is also an FDA approved as a food additive. Xylitol will be used as a treatment for the decolonization of C. difficile and will be given in gel capsules. The xylitol provided will be prepared by the BWH investigational drug service and ordered from MEDISCA suppliers. It will be 100% pure. Xylitol has a distinct taste and therefore it will be administered in gel capsules as opposed to an oral solution to maintain blinding.<br>|
| Placebo Comparator: Sucralose<br>Patients in this arm will be receiving 250mg/day of sucralose over a 4 week period. | Drug: Sucralose<br>* The placebo in this trial will be sucralose. Sucralose is alternate SA that is poorly absorbed and non-microbially metabolized by bacteria in the microbiome including C. difficile. Because this is a double-blind, controlled trial, the control will be presented in capsules that are identical in size, smell, texture, and appearance to those of the xylitol capsules. These will be produced by the BWH investigational drug service. Sucralose will be ordered from MEDISCA as well and will be 100% pure.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C.difficile decolonization | Absence of C. difficile via PCR in week 8 stool sample | 8 weeks | 
| safety and tolerability | Subject incidence of treatment-emergent adverse events (including treatment-emergent adverse events for clinically significant changes in laboratory parameters and vital signs) | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| biomass of C.difficile | Change in biomass of C. difficile | 8 weeks | 
| IBD clinical outcomes | Clinical Remission: SCCAI score less than 3 & HBI score less than 5 Clinical Response: A decrease from baseline in the HBI score or SCCAI score by three points | 8 weeks | 
| IBD clinical outcomes | Clinical Remission: SCCAI score less than 3 & HBI score less than 5 Clinical Response: A decrease from baseline in the HBI score or SCCAI score by three points | 52 weeks | 
| C. difficile infection | Incidence of patients developing CDI | 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn's Disease, Ulcerative colitis