Ulcerative Colitis
Conditions
Brief summary
The purpose of this study is to evaluate the engraftment of donor microbiota with active ulcerative colitis (UC) following sequential fecal microbiota transplant (FMT). One key group of bacteria we are following are sulfate reducing bacteria (SRB). We plan to measure the relative abundance of SRB at baseline and after FMT. It is widely unknown if the microbiota in UC is dysfunctional and therefore perpetuates inflammation, or if the ongoing inflammation shapes the microbiota. We aim to determine if we can alter the microbiota in UC towards a healthy, more diverse microbiota resembling the donor using capsule FMT material.
Detailed description
Inflammatory bowel disease (IBD) is a chronic, relapsing remitting inflammatory disease of the intestine. The two main forms of IBD are Crohn's disease (CD) and Ulcerative Colitis (UC). There is no cure for IBD and the etiology is unknown, however IBD is thought to arise as an aberrant immune response to the intestinal microbiota. The intestinal microbiota closely correlates with inflammation in IBD. Currently, the treatment of IBD is based on suppressing the aberrant immune response in the intestine. This often takes the form of systemic immunosuppression, which in turn carries a multitude of risks including infection and malignancy. Thus there is an urgent need for safe, effective therapies that ultimately have the potential to cure IBD. Fecal microbiota transplantation (FMT) is the process of transferring fecal microbiota from one individual to another. FMT has revolutionized the treatment of multiple recurrent Clostridium difficile infection with a cure rate around 90%. Given the success of FMT in C. difficile colitis, attention turned to other forms of colitis, in particular IBD. Early pilot studies demonstrated a mixed result for the use of FMT in IBD. One of the key issues surrounding the use of FMT in IBD is the challenge of engrafting a new microbiota. Additionally IBD flares following FMT for C. difficile infection have been reported, although it is difficult to account for the confounding of the underlying C. difficile infection. This study will examine how FMT donor selection can impact the engraftment of the microbiota into patients with UC.
Interventions
DRUGFecal microbiota
Lyophilized encapsulated fecal microbiota given daily for 8 weeks.
DRUGPlacebo
Placebo capsules identical in appearance to fecal microbiota capsules to be taken daily for 8 weeks.
Sponsors
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 89 Years
Healthy volunteers
No
Inclusion criteria
* Able and willing to provide consent * English speaking * Diagnosis of ulcerative colitis based on typical clinical-histopathic diagnosis * Diagnosis of ulcerative colitis \> 3 months * Active disease on endoscopy (endoscopic Mayo subscore ≥ 1) * Evidence of inflammation extending beyond a minimum of 20cm * Any ongoing ulcerative colitis therapy must be at stable doses for 4 weeks prior to study and remain stable over the course of the study
Exclusion criteria
* Extensive bowel resection * Presence of ileostomy or colostomy * Suspicion of ischemic colitis, radiation colitis or microscopic colitis * Diagnosis of Crohn's disease * Diagnosis of per-anal fistula or abscess * Adenomatous polyps that have not been removed * Use of pre or probiotics within 30 days of randomization * Pregnancy * Severe food allergies * End stage liver disease or cirrhosis * An absolute neutrophil count \< 500 cell/µL * Life expectancy \< 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Engraftment of donor microbiota | 12 weeks | Engraftment measured by SourceTracker at baseline to week 12 between FMT arm and placebo arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical efficacy of FMT versus placebo | 8 weeks | Change in partial Mayo score from baseline to week 8 between FMT and placebo arm |
| Clinical efficacy of low sulfate reducing microbiota | 12 weeks | Partial mayo score at week 12 between those with low sulfate reducing microbiota or not low sulfate reducing microbiota |
| Rate of change of sulfate reducing microbiota | 4 weeks | Change in quantitative PCR of sulfate reducing genes at week 1, 2, 3 and 4 between FMT arm and placebo arm |
| Serious adverse events | 12 weeks | Number of serious adverse events between FMT arm and placebo arm |
Countries
United States
Outcome results
None listed