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

Phase 2

Completed

Conditions: Ulcerative Colitis
Inflammatory Bowel Diseases

Interventions: Drug: Fecal Microbiota Transplantation
Dietary Supplement: Psyllium Husk Powder

Registration Number: NCT03998488

Lead Sponsor: Weill Medical College of Cornell University

Brief Summary: 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: This is a randomized, double-blind, placebo-controlled clinical trial with the following treatment assignments:

1. Investigational FMT (one-time)

1. Subject will blindly receive investigational FMT once at day 0 colonoscopy

2. Subjects in this group will blindly receive placebo FMP250 at week 8 by flexible sigmoidoscopy.

2. Investigational FMT (one-time) + Psyllium (2x/day for 8 weeks)

1. Subject will blindly receive investigational FMT once at day 0 colonoscopy

2. Subjects in this group will blindly receive placebo FMP250 at week 8 by flexible sigmoidoscopy.

3. Placebo FMT (one-time) +/- Psyllium (2x/day for 8 weeks)

1. Subject will blindly receive placebo FMT once at day 0 colonoscopy

2. 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 27

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:
1. Urine Testing
2. Blood Testing
3. 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
1. Hb: < 8
2. 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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Investigational FMT	Fecal Microbiota Transplantation	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.
Investigational FMT + psyllium fiber	Fecal Microbiota Transplantation	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.
Investigational FMT + psyllium fiber	Psyllium Husk Powder	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.
Placebo FMT +/- psyllium fiber	Psyllium Husk Powder	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.

Primary Outcome Measures

Name	Time	Method
Clinical Response	Week 8 post-FMT	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

Secondary Outcome Measures

Name	Time	Method
Clinical Remission	Week 8 post-FMT	Clinical remission at week 8 post-FMT, as defined by Mayo score ≤ 2 without any subscore \>1
Endoscopic Response or Remission	Week 8 post-FMT	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
Number of Treatment or Disease Related Adverse Events.	Week 0 Colonoscopy - Week 12 post-FMT, 6 months post-FMT, and 1 year post-FMT	Adverse event counts are cumulative frequencies of adverse and severe adverse events assessed at Week 0 Colonoscopy - Week 12 post-FMT, 6 months post-FMT, and 1 year post-FMT.