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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| FMT Treatment | Active Comparator | Fecal microbiota - 1.0-3.0 x 10^11 CFU / day (2 capsules per day for 8 weeks). |
|
| Placebo | Placebo Comparator | The placebo consists of a mixture of trehalose and crystalline methylcellulose (Avicel) in 6:1 (w/w) ratio that is packaged in size 0 swedish orange capsules, which are then double encapsulated in size 00 natural colored capsules to make them visibly indistinguishable from encapsulated active product. Two capsules taken daily for 8 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fecal microbiota | Drug | Lyophilized encapsulated fecal microbiota given daily for 8 weeks. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Engraftment of donor microbiota | Engraftment measured by SourceTracker at baseline to week 12 between FMT arm and placebo arm. | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical efficacy of FMT versus placebo | Change in partial Mayo score from baseline to week 8 between FMT and placebo arm | 8 weeks |
| Clinical efficacy of low sulfate reducing microbiota | Partial mayo score at week 12 between those with low sulfate reducing microbiota or not low sulfate reducing microbiota |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Byron Vaughn, MD | University of Minnesota | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Minnesota | Minneapolis | Minnesota | 55455 | United States |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| ICF | No | No | Yes | Informed Consent Form | Oct 8, 2021 | Mar 12, 2024 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D003093 | Colitis, Ulcerative |
| ID | Term |
|---|---|
| D003092 | Colitis |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D000069467 | Fecal Microbiota Transplantation |
| ID | Term |
|---|---|
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
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| Placebo |
| Drug |
Placebo capsules identical in appearance to fecal microbiota capsules to be taken daily for 8 weeks. |
|
| 12 weeks |
| Rate of change of sulfate reducing microbiota | Change in quantitative PCR of sulfate reducing genes at week 1, 2, 3 and 4 between FMT arm and placebo arm | 4 weeks |
| Serious adverse events | Number of serious adverse events between FMT arm and placebo arm | 12 weeks |
| D015212 |
| Inflammatory Bowel Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |