Inflammatory bowel disease is a condition caused by gastrointestinal immune system dysregulation and affected by both genetic and environmental factors. Differences in intestinal bacteria exist between IBD patients and healthy controls, but the role of intestinal bacteria in the development and treatment of IBD remains largely unknown. Fecal microbiota transplantation (FMT) is the transfer of gastrointestinal bacteria from a healthy donor to a patient with altered microbial diversity with the intent of restoring a normal bacterial balance. Most studies focus on its use in treating Clostridium difficile (CDI), an infection characterized by dysbiosis. Given the role of dysbiosis in IBD, the investigators hypothesize that FMT may be beneficial in IBD. The purpose of this study is to prospectively examine the safety of FMT in the management of ulcerative colitis (UC).
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) with significant morbidity and mortality. Current therapies remain limited by side effects and loss of response over time, and there is an ongoing need for new therapies. Fecal microbiota transplantation (FMT), which has proven to be safe and effective in the management of Clostridium difficile infection (CDI) has been proposed as a therapy for UC. There have been studies examining the role of FMT in UC, but they have shown mixed results, and have not examined the underlying immunologic and microbial changes to explain how and why FMT works from specific donors and in certain recipients. Furthermore, no studies have examined the long-term safety of FMT in patients with UC. This proposal aims to examine: (a) the short- and long-term safety of FMT in patients with UC, (b) the efficacy of FMT as a therapy for mild-moderate UC, and (c) the microbial and immunologic changes that occur after FMT, to help understand how and why it works in this group of patients.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
We will use fecal microbiota transplantation (FMT), with fecal material obtained from OpenBiome or donor directed, to assess safety (as primary outcome) and efficacy (as secondary outcome) in adult (\>18 year old) patients with active ulcerative colitis (UC).
Weill Cornell Medical College
New York, New York, United States
Safety post-FMT as determined by interview for adverse events
Patient information regarding adverse events and safety of FMT for UC will be collected throughout the study period, including day 0, weeks 1, 2, 4, 6, 12 24, and then every 6 months until 36 months post-FMT. Throughout the study period, patients will be assessed for safety with questions regarding general well-being (such as "how have you been feeling?"), as well as specific questions to evaluate for occurrence of adverse events. Patients will also be questioned regarding stool form and frequency, presence of abdominal pain, fevers and subjective well-being.
Time frame: 36 months post-FMT
Clinical remission
Defined by Mayo score ≤ 2 without any subscore \>1, and Mayo endoscopic subscore 0-1
Time frame: 2, 4 and 12 weeks post fecal microbiota transplantation
Clinical Response
Defined by decrease in Mayo score by 3 points, decrease in bleeding subscore by 1, or absolute subscore of 0-1
Time frame: 2, 4 and 12 weeks post fecal microbiota transplantation
Progression of disease defined by initiation of anti-TNF agents
Initiation of anti-TNF agents (such as infliximab, adalimumab, certolizumab), vedolizumab, steroids. Includes time gap until additional agents are started
Time frame: 2, 4 and 12 weeks post fecal microbiota transplantation
Progression of disease defined by increase in dosages of current UC medications
Increase in dosages of current ulcerative colitis specific medications
Time frame: 2, 4 and 12 weeks post fecal microbiota transplantation
Progression of disease defined by time to colectomy
Time to colectomy rates and increase in time to colectomy
Time frame: up to three year follow-up period post fecal microbiota transplantation
Death secondary to UC
Time to death secondary to ulcerative colitis
Time frame: Anytime during the three year follow-up period post fecal microbiota transplantation
Progression of disease defined by clinical flare
Time to next flare
Time frame: 2, 4 and 12 weeks post fecal microbiota transplantation
Microbial changes
\- Alterations in microbial profiles as defined by sequence of genetic material from fecal material.
Time frame: 0, 2 and 4 weeks post fecal microbiota transplantation
Immunological changes
\- Alterations in immune cell function as defined by RNA sequencing and flow cytometry
Time frame: 0, 2 and 4 weeks post fecal microbiota transplantation
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