Immune-related colitis from immune checkpoint inhibitors (ICI) is a common adverse effect causing significant morbidity and impairment of quality of life (QoL). Steroids are the first line of treatment for severe ICI induced Immune- mediated diarrhea and colitis (IMDC). If there is no improvement in 48 to 72 hours, other immunosuppressive agents (infliximab, vedolizumab) are recommended. However, efficacy data supporting the use of immunosuppressives for steroid refractory IMDC is limited by case reports/series. Clinical trials focusing on steroid-refractory colitis are sparse. Novel treatments for IMDC outside of blanket immunosuppression are needed. There is robust evidence to suggest that gut microbial diversity and composition is associated with both ICI efficacy and toxicity. Preliminary studies have shown that pathophysiology of immune mediated colitis may be related to loss of gut microbial diversity. Recently, multiple case series have shown the utility of fecal microbiota transplant for treatment of refractory IMDC providing the proof of concept. This is a pilot randomized placebo controlled study to assess the safety and feasibility of oral restorative microbiota therapy (RMT) in patients with steroid- refractory IMDC.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
DOUBLE
A single loading dose of RMT capsules containing \~5 x 10 11 bacteria on day 1 followed by 2 x 10 11 bacteria daily for 6 days. The RMT capsule preparation (\~2-5 capsules, size 00) is self-administered on an empty stomach with at least one glass of water. Clear liquids are allowed, and food can be resumed 2 hours after administration.
Participants will receive an identical looking placebo capsules daily for 7 days (i.e 5 placebo capsules on day 1), followed by 2 placebo capsules daily from Day 2-7. The placebo capsule preparation is self-administered on an empty stomach with at least one glass of water. Clear liquids are allowed, and food can be resumed 2 hours after administration.
Essentia Health St. Joseph's Medical Center
Brainerd, Minnesota, United States
Essentia Health Deer River Clinic
Deer River, Minnesota, United States
Essentia Health St. Mary's Detroit Lakes Clinic
Detroit Lakes, Minnesota, United States
Essentia Health Cancer Center
Duluth, Minnesota, United States
Essentia Health Fosston
Fosston, Minnesota, United States
Essentia Health Hibbing Clinic
Hibbing, Minnesota, United States
University of Minnesota
Minneapolis, Minnesota, United States
Essentia Health Sandstone
Sandstone, Minnesota, United States
Essentia Health Virginia Clinic
Virginia, Minnesota, United States
Feasibility and safety of RMT
Feasibility and safety of RMT as assessed by the occurrence of adverse events
Time frame: 6 months after baseline
Clinical remission by Day 10
Proportion of patients who experience diarrhea resolution to Grade \<= 1 of refractory IMDC at Day 10 from 1st dose of RMT
Time frame: Day 10
Clinical remission by Day 30
Incidence of clinical remission of refractory IMDC at Day 30 following first dose of RMT
Time frame: Day 30
Time for clinical remission
Days to induce a clinical remission of refractory IMDC necessary to achieve a diarrhea of Grade \<= 1
Time frame: Day 180
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