Examining the Efficacy of Fecal Microbiota Transplantation (FMT) and Dietary Fiber in Patients With Ulcerative Colitis

Study Overview
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Brief Summary
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A double-blind, randomized, placebo-controlled clinical trial examining the efficacy and safety of Fecal Microbiota Transplantation (FMT) and high fiber supplementation in patients with active mild to moderate Ulcerative Colitis (UC). All enrolled subjects will provide serological, stool and mucosal specimen at each clinic visit to help further define the alterations in microbial profiles and immune cell function in response to psyllium fiber after FMT treatment.

Detailed Description
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This is a randomized, double-blind, placebo-controlled clinical trial with the following treatment assignments: Investigational FMT (one-time) Subject will blindly receive investigational FMT once at day 0 colonoscopy Subjects in this group will blindly receive placebo FMP250 at week 8 by flexible sigmoidoscopy. Investigational FMT (one-time) + Psyllium (2x/day for 8 weeks) Subject will blindly receive investigational FMT once at day 0 colonoscopy Subjects in this group will blindly receive placebo FMP250 at week 8 by flexible sigmoidoscopy. Placebo FMT (one-time) +/- Psyllium (2x/day for 8 weeks) Subject will blindly receive placebo FMT once at day 0 colonoscopy Subjects in this group will blindly receive investigational FMP250 at week 8 by flexible sigmoidoscopy. Subjects will blindly receive the investigational or placebo FMP250 treatment if they meet all inclusion and exclusion criteria during the day 0 screening colonoscopy. Subjects will receive follow-up phone calls at day 1, week 2, week 6, and week 10 post-FMT and will return for clinic visits at week 4, week 8 and week 12 post-FMT. Stool and blood samples will be collected for research purposes from subjects at every clinic visit (Day 0 colonoscopy, Week 4, Week 8, and Week 12). Mucosal biopsies will also be taken during the initial colonoscopy, at day 0 and during the follow-up flexible sigmoidoscopy at week 8. At week 8 post-FMT, all subjects will be evaluated by flexible sigmoidoscopy. Subjects originally randomized into the placebo cohort at week 0 will receive investigational FMP250 by flexible sigmoidoscopy at week 8, and subjects originally randomized into the investigational cohort at week 0 will receive placebo FMP250 by flexible sigmoidoscopy at week 8. Lastly, all subjects will be contacted for follow-up phone calls every subsequent 6 months for the next year.

Official Title
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A Randomized, Placebo-controlled Clinical Trial Examining the Efficacy of Fecal Microbiota Transplantation (FMT) and Subsequent Dietary Fiber in Patients With Moderate Ulcerative Colitis

Conditions
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Ulcerative Colitis, Inflammatory Bowel Diseases

Intervention / Treatment
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* Drug: Fecal Microbiota Transplantation
* Dietary Supplement: Psyllium Husk Powder


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female ≥ 18 years of age. Documentation of prior history of mild to moderate UC. Endoscopy confirmed active UC ≥ 15 centimeters at week 0 screening colonoscopy. a. As defined by a total Mayo scoring of 4-10 with an endoscopic sub-score ≥ 1. Patients must have a descending intact colon. Patients taking steroid or biologic therapy must be on a stable dose for 4 weeks prior to screening and maintained throughout the trial. Eligible patients willing to undergo screening testing prior to FMT to document baseline status: Urine Testing Blood Testing Stool Testing Patients must discontinue anti-rCDI antibiotics (e.g. vancomycin, fidaxomicin) 48 hours prior to FMT delivery procedure. Exclusion Criteria: Biopsy proven Crohn's disease UC patients with severe disease (defined as a total mayo score >10) Clinical complications requiring emergent management (e.g. stricture, bowel obstruction, perforation and/or abscess) Concurrent C. difficile or other infections Primary sclerosing cholangitis Prior history of FMT Treatment for malignancy within past 5 years Active or latent tuberculosis Clinically meaningful laboratory abnormalities Hb: < 8 ALT: greater than 3x the ULN (upper limit of normal) History of anaphylactic reactions to food allergens or allergy to psyllium husk Subject having any other condition that, in the opinion of the investigator, would jeopardize the safety or rights of the subject participating in the study, would make it unlikely for the subject to complete the study, or would confound the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Eligible subjects will be randomly assigned to one of the three (Placebo or Investigational FMT +/- Psyllium) treatment groups. A series of randomized blocks of 6-10 will be generated with a 1:1:1 allocation ratio.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Investigational FMT<br>Participants will be blindly randomized to receive a single dose of investigational FMT during the week 0 colonoscopy. Additionally, participants will blindly receive a single dose of placebo FMT during the week 8 by flexible sigmoidoscopy. | Drug: Fecal Microbiota Transplantation<br>* The proposed intervention will deliver 250 milliliters of FMT by colonoscopy to the investigational FMT treatment groups at week 0. The placebo treatment group will instead receive the placebo FMT by colonoscopy at week 0 and then the investigational FMT by flexible sigmoidoscopy at week 8. Investigational FMT is biologically active human fecal material that is pre-screened, tested, quarantined, stored, packaged, and labeled by OpenBiome. Placebo FMP250 is a control unit made of glycerol, saline, and food dye that is stored, packaged, and labeled identically to the investigational FMT, to ensure blinding during delivery.<br>* Other names: FMT;|
| Active Comparator: Investigational FMT + psyllium fiber<br>Participants will be blindly randomized to receive a single dose of investigational FMT during the week 0 colonoscopy. They will also receive fiber supplementation of 1 teaspoon 2x/day for 8 weeks. Additionally, participants will blindly receive a single dose of placebo FMT during the week 8 by flexible sigmoidoscopy. | Drug: Fecal Microbiota Transplantation<br>* The proposed intervention will deliver 250 milliliters of FMT by colonoscopy to the investigational FMT treatment groups at week 0. The placebo treatment group will instead receive the placebo FMT by colonoscopy at week 0 and then the investigational FMT by flexible sigmoidoscopy at week 8. Investigational FMT is biologically active human fecal material that is pre-screened, tested, quarantined, stored, packaged, and labeled by OpenBiome. Placebo FMP250 is a control unit made of glycerol, saline, and food dye that is stored, packaged, and labeled identically to the investigational FMT, to ensure blinding during delivery.<br>* Other names: FMT;Dietary Supplement: Psyllium Husk Powder<br>* All subjects assigned to the fiber treatment arms will be required to take 1 teaspoon (approximately 5 grams) of psyllium husk powder twice a day (morning and night) for 8 weeks, beginning 3 days prior to Week 0 screening colonoscopy. Psyllium husk powder is the dried and powdered form of a psyllium seed coat.<br>|
| Placebo Comparator: Placebo FMT +/- psyllium fiber<br>Participants will be blindly randomized to receive a single dose of placebo FMT during the week 0 colonoscopy. They may or may not also receive fiber supplementation of 1 teaspoon 2x/day for 8 weeks. Additionally, participants will blindly receive a single dose of investigational FMT during the week 8 by flexible sigmoidoscopy. | Dietary Supplement: Psyllium Husk Powder<br>* All subjects assigned to the fiber treatment arms will be required to take 1 teaspoon (approximately 5 grams) of psyllium husk powder twice a day (morning and night) for 8 weeks, beginning 3 days prior to Week 0 screening colonoscopy. Psyllium husk powder is the dried and powdered form of a psyllium seed coat.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Response | Clinical response at week 8 post-FMT, as defined by the reduction of the Mayo scoring system by >3 points (+30% reduction) with an accompanying decrease in the sub-score for rectal bleeding of at least 1 point | Week 8 post-FMT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Remission | Clinical remission at week 8 post-FMT, as defined by Mayo score ≤ 2 without any subscore >1 | Week 8 post-FMT | 
| Endoscopic Response or Remission | Endoscopic response or remission at week 8 post-FMT, as defined by a Mayo endoscopic sub-score 0-1 with at least a 1-point reduction from baseline or a Mayo endoscopic sub-score of 0 | Week 8 post-FMT | 
| Number and type of treatment related adverse events. |  | Week 0 Colonoscopy - Week 12 post-FMT | 
| Change in Number of disease-related complications such as hospitalizations, surgeries and endoscopies, medical complications, and mortality |  | Week 0 Colonoscopy - Week 12 post-FMT | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fecal Microbiota Transplantation, Inflammatory Bowel Diseases, FMT