Fecal Microbiota Transplantation for Ulcerative Colitis
Fecal microbiota therapy (FMT) is an emerging treatment for gastrointestinal disorders marked by an imbalance in the intestinal microbial flora (dysbiosis). It is hypothesized to work by shifting the recipient's microbiota toward a eubiotic microbial community that resists colonization by pathogenic organisms or decreases its inherent inflammatory properties. Several studies now report its efficacy in treatment of severe Clostridium difficile colitis. Preliminary studies using FMT in Ulcerative Colitis (UC) have also met with some success. This is corroborated by several lines of evidence suggesting dysbiosis plays an important role in UC pathogenesis. While a recent study using FMT in patients with irritable bowel syndrome (IBS) and constipation found transplants persist for up to 2 years, the extent to which the microbiota is alterable in UC is not known. Indeed, there may be particular genetic or immunologic factors in UC leading to selection pressure preventing a change in the microbiota. As an initial step into investigating the potential efficacy of stool transplants for Ulcerative Colitis (UC), the investigators propose to determine the feasibility and stability of transplanted microbiota in a series of 10 patients with mild to moderate UC.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
|Official Title:||Evaluation of Durability of Fecal Microbiota Transplantation in Patients With Mild to Moderate Ulcerative Colitis|
- Successful engraftment of donor fecal microbiota at 4 weeks post-tranplantation. [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]Both weighted and unweighted UniFrac distances will be calculated in this study. A relative difference of UniFrac distances comparing recipient and donor stool at baseline (inter-individual) and comparing recipient stool prior to transplant at two time points (intra-individual) for each donor recipient pair will be calculated. This value multiplied by 50% will be the threshold value (TV) to determine if the transplant engrafts and is stable. Unifrac distances comparing the recipient pre- and post- transplant will need to be >(intra-individual variation of the recipient+TV). In addition, Unifrac distances comparing the recipient post-transplant with the donor will need to be <(intra-individual variation of the donor+TV). Successful engraftment will be defined as meeting both these criteria.
- Engraftment of fecal microbiota transplantation at 7 days. [ Time Frame: 7 days ] [ Designated as safety issue: No ]As in primary aim but at 7 days.
- Durability of Fecal Microbiota Transplantation at 12 weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]As in primary aim but at 12 weeks.
- Clinical remission at 4 weeks. [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]Defined as Mayo score <=2 with no subscore >1
- Clinical remission at 12 weeks. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]Defined as Mayo score <=2 with no subscore >1
- Endoscopic remission at 4 weeks. [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]Mayo endoscopy scope of 0.
- Number of patients with worsened disease. [ Time Frame: 4 weeks. ] [ Designated as safety issue: Yes ]Increase in Mayo score of >2.
- Number of adverse events. [ Time Frame: 12 weeks. ] [ Designated as safety issue: Yes ]
|Study Start Date:||October 2012|
|Estimated Study Completion Date:||July 2013|
|Estimated Primary Completion Date:||April 2013 (Final data collection date for primary outcome measure)|
Experimental: Fecal Microbiota Transplantation
Fecal Microbiota Transplantation by colonoscopic delivery of stool to the right colon.
Other: Fecal Microbiota Transplantation
Fecal microbiota transplantation by colonoscopic administration of 300cc of fecal slurry from healthy donor to the right colon.
|Contact: Timothy L Zisman, MD||(206) 598-4377||TZisman@medicine.washington.edu|
|United States, Washington|
|University of Washington||Recruiting|
|Seattle, Washington, United States, 98103|
|Principal Investigator:||Timothy L Zisman, MD||University of Washington|