Low Sulfur Fecal Transplant for Ulcerative Colitis

• ClinicalTrials.gov Identifier: NCT03948919
• Recruitment Status: Active, not recruiting
• First Posted: May 14, 2019
• Last Update Posted: February 8, 2023
• Sponsor: University of Minnesota
• Information provided by (Responsible Party): University of Minnesota

Tracking Information

• First Submitted Date: May 10, 2019
• First Posted Date: May 14, 2019
• Last Update Posted Date: February 8, 2023
• Actual Study Start Date: July 31, 2019
• Estimated Primary Completion Date: May 31, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 10, 2019)

Engraftment of low sulfate reducing microbiota [ Time Frame: 12 weeks ]

Change in quantitative PCR of sulfate reducing genes from baseline to week 12 between FMT arm and placebo arm.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 10, 2019)

• Rate of change of sulfate reducing microbiota [ Time Frame: 4 weeks ]
  Change in quantitative PCR of sulfate reducing genes at week 1, 2, 3 and 4 between FMT arm and placebo arm
• Clinical efficacy of FMT versus placebo [ Time Frame: 8 weeks ]
  Change in partial Mayo score from baseline to week 8 between FMT and placebo arm
• Clinical efficacy of low sulfate reducing microbiota [ Time Frame: 12 weeks ]
  Partial mayo score at week 12 between those with low sulfate reducing microbiota or not low sulfate reducing microbiota
• Serious adverse events [ Time Frame: 12 weeks ]
  Number of serious adverse events between FMT arm and placebo arm

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Low Sulfur Fecal Transplant for Ulcerative Colitis
• Official Title: Low Sulfur Fecal Transplant for Ulcerative Colitis
• Brief Summary: The purpose of this study is to evaluate the engraftment of donor microbiota's sulfate reducing bacteria (SRB) in subjects with active ulcerative colitis (UC) following sequential fecal microbiota transplant (FMT). Specifically this study will evaluate if low SRB donor microbiota translates to lower SRB microbiota in the UC recipient. It is widely unknown if the microbiota in UC is dysfunctional and therefore perpetuates inflammation, or if the ongoing inflammation shapes the microbiota. Patients with UC have a higher relative abundance of SRB compared to healthy controls. It is the aim of this study to determine if the microbiota in UC can be altered to favor a low SRB fraction.

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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Basic Science
• Condition: Ulcerative Colitis

Intervention

• Drug: Fecal microbiota
  Lyophilized encapsulated fecal microbiota given daily for 8 weeks.
• Other: Placebo
  Placebo capsules identical in appearance to fecal microbiota capsules to be taken daily for 8 weeks.

Study Arms

• Active Comparator: FMT Treatment
  Fecal microbiota - 1.0-3.0 x 10^11 CFU / day (2 capsules per day for 8 weeks).
  Intervention: Drug: Fecal microbiota
• Placebo Comparator: Placebo
  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.
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: May 10, 2019): 20
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2023
• Estimated Primary Completion Date: May 31, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 89 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03948919
• Other Study ID Numbers: GI-2019-27285
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: University of Minnesota
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Minnesota
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Byron Vaughn, MD; University of Minnesota

• PRS Account: University of Minnesota
• Verification Date: February 2023