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This is a randomized, placebo-controlled, dose-ranging study to assess the safety and efficacy of xylitol as an oral therapeutic for decolonization of C. difficile in IBD patients. A total of 99 patients who meet eligibility criteria will be randomized 1:1:1 to one of two xylitol doses or placebo arm. All arms will receive an identical capsule dosing for four weeks. Microbiome assessment and C. difficile testing will be performed at baseline, week 4, 8, 26, and 52.
This randomized placebo-controlled dose-finding 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 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 screening. Participants will be screened for C. difficile colonization via colonic wash sampling during colonoscopy or whole stool following a clinic appointment.
Participants may only have inactive or mild IBD based in clinical scores (see inclusion criteria) to be eligible for screening. Risk factors for colonization will be assessed by comparing colonized vs. not colonized patients.
Participants who are found to be colonized will be randomized 1:1:1 to either placebo or one of two dosing groups of xylitol. The dose A treatment arm will receive 7.5 grams daily of xylitol via gel capsule for 4 weeks. The dose B treatment arm will receive 15 grams daily of xylitol via gel capsule for 4 weeks. The placebo arm will receive identical capsule dosing for 4 weeks. Participants will end dosing at week 4, but monitoring will continue through week 52. Both participants and study team will be blinded to treatment arm allocation.
The primary endpoints assessed are decolonization at week 8 as well as safety and tolerability through week 8. In addition, secondary efficacy outcomes including IBD disease activity and development of CDI, which will be evaluated at week 8, week 26 and week 52. Disease activity and symptoms will be recorded from informed consent through 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose A of Xylitol | Experimental | Patients in this arm will be receiving 7.5g/day of Xylitol over a 4 week period. |
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| Dose B of Xylitol | Experimental | Patients in this are will be receiving 15g/day of Xylitol over a 4 week period. |
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| Placebo | Placebo Comparator | Patients in this arm will be receiving placebo over a 4 week period. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Xylitol | Drug | 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. |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| biomass of C.difficile | Change in biomass of C. difficile | 8 weeks |
| IBD clinical outcomes | Clinical Remission: Partial Mayo score less than 1 & HBI score less than 5 Clinical Response: A decrease from baseline in the HBI score or SCCAI score by three points |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Heidy Cabral | Contact | 6175257322 | hjcabral@bwh.harvard.edu | |
| Jessica Allegretti, MD | Contact | 6177326389 | jallegretti@bwh.harvard.edu |
| Name | Affiliation | Role |
|---|---|---|
| Jessica R Allegretti, MD | Brigham and Women's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brigham and Women's Hospital | Boston | Massachusetts | 02115 | United States |
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| ID | Term |
|---|---|
| D015212 | Inflammatory Bowel Diseases |
| D003015 | Clostridium Infections |
| D003424 | Crohn Disease |
| D003093 | Colitis, Ulcerative |
| ID | Term |
|---|---|
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D007410 | Intestinal Diseases |
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| ID | Term |
|---|---|
| D014993 | Xylitol |
| ID | Term |
|---|---|
| D013402 | Sugar Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D002241 | Carbohydrates |
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| Placebo | Drug | The placebo will be administered by the BWH investigational drug services. The placebo will be composed of cellulose microcrystal. |
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| 8 weeks |
| IBD clinical outcomes | Clinical Remission: Partial Mayo score less than 1 & 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 |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D003092 | Colitis |
| D003108 | Colonic Diseases |