Clostridioides Difficile Infection, Inflammatory Bowel Diseases
Conditions
Keywords
Crohn's Disease, Ulcerative colitis
Brief summary
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.
Detailed description
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.
Interventions
DRUGXylitol
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.
DRUGPlacebo
The placebo will be administered by the BWH investigational drug services. The placebo will be composed of cellulose microcrystal.
Sponsors
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 ≤ 7; Partial Mayo score ≤ 4) 5. Presenting for outpatient colonoscopy or clinic appointment for any indication
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. Stool positive for Listeria monocytogenes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| C.difficile decolonization | 8 weeks | Absence of C. difficile via PCR in week 8 stool sample |
| safety and tolerability | 8 weeks | Subject incidence of treatment-emergent adverse events (including treatment-emergent adverse events for clinically significant changes in laboratory parameters and vital signs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| biomass of C.difficile | 8 weeks | Change in biomass of C. difficile |
| IBD clinical outcomes | 8 weeks | 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 |
| C. difficile infection | 52 weeks | Incidence of patients developing CDI |
Countries
United States
Contacts
CONTACTHeidy Cabral
CONTACTJessica Allegretti, MD
PRINCIPAL_INVESTIGATORJessica R Allegretti, MD
Brigham and Women's Hospital
Outcome results
None listed