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

Ulcerative Colitis Clinical Trial

— MINDFUL  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03998488
• Other study ID #: 19-04020045
• Secondary ID: 5R01DK128257
• Status: Completed
• Phase: Phase 2
• Start date: January 31, 2020
• Est. completion date: April 12, 2024

Study information

• Verified date: May 2024
• Source: Weill Medical College of Cornell University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: April 12, 2024
• Est. primary completion date: June 9, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 89 Years

Eligibility

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.

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Inflammatory Bowel Diseases
• Intestinal Diseases
• Ulcer
• Ulcerative Colitis

Intervention

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.

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.

Locations

Country	Name	City	State
United States	Weill Cornell Medicine	New York	New York

Sponsors (4)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	Crohn's and Colitis Foundation, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Clinical Remission	Clinical remission at week 8 post-FMT, as defined by Mayo score = 2 without any subscore >1	Week 8 post-FMT
Secondary	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
Secondary	Number of Treatment or Disease Related Adverse Events.	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.	Week 0 Colonoscopy - Week 12 post-FMT, 6 months post-FMT, and 1 year post-FMT