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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Inflammatory Bowel Diseases; Ulcerative Colitis
• Intervention / Treatment: Drug: Fecal Microbiota Transplantation; Dietary supplement: Psyllium Husk Powder

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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Fatiha Chabouni, MD; Email: fac2005@med.cornell.edu
• Study Contact Backup: Name: Nancy Tran, BS; Phone Number: 646-697-0985; Email: nat4010@med.cornell.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Investigational FMT; 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; 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.; Other Names: FMT; FMP250
Active Comparator: Investigational FMT + psyllium fiber; 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; 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.; Other Names: FMT; FMP250; Dietary supplement: Psyllium Husk Powder; 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.
Placebo Comparator: Placebo FMT +/- psyllium fiber; 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; 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.

What is the study measuring?

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 or Disease Related Adverse Events.	Adverse event counts are cumulative counts assessed at Week 0 Colonoscopy - Week 12 post-FMT, 6 months post-FMT, and 1 year post-FMT.	Week 0 Colonoscopy - Week 12 post-FMT, 6 months post-FMT, and 1 year post-FMT

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institutes of Health (NIH); Crohn's and Colitis Foundation
• Investigators: Principal Investigator: Randy Longman, MD, PhD, Weill Medical College of Cornell University

Publications and helpful links

General Publications

• Jacob V, Crawford C, Cohen-Mekelburg S, Viladomiu M, Putzel GG, Schneider Y, Chabouni F, O'Neil S, Bosworth B, Woo V, Ajami NJ, Petrosino JF, Gerardin Y, Kassam Z, Smith M, Iliev ID, Sonnenberg GF, Artis D, Scherl E, Longman RS. Single Delivery of High-Diversity Fecal Microbiota Preparation by Colonoscopy Is Safe and Effective in Increasing Microbial Diversity in Active Ulcerative Colitis. Inflamm Bowel Dis. 2017 Jun;23(6):903-911. doi: 10.1097/MIB.0000000000001132.

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2020
• Primary Completion (Actual): June 9, 2023
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: June 24, 2019
• First Submitted That Met QC Criteria: June 24, 2019
• First Posted (Actual): June 26, 2019

Study Record Updates

• Last Update Posted (Actual): April 2, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Fecal Microbiota Transplantation; FMT; Inflammatory Bowel Diseases
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Ulcer; Inflammatory Bowel Diseases; Intestinal Diseases; Colitis; Colitis, Ulcerative; Gastrointestinal Agents; Cathartics; Antidiarrheals; Psyllium; Calcium polycarbophil
• Other Study ID Numbers: 19-04020045; 5R01DK128257 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No