Clinical trial NCT03998488: Examining the Efficacy of Fecal Microbiota Transplantation (FMT) and Dietary Fiber in Patients With Ulcerative Colitis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ulcerative Colitis
Inflammatory Bowel Diseases
Keywords: FMT
Fecal Microbiota Transplantation
Inflammatory Bowel Diseases
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: Crohn's and Colitis Foundation
name: National Institutes of Health (NIH)
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2019-06-26
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Clinical Response
timeFrame: Week 8 post-FMT
Secondary outcomes:
measure: Clinical Remission
timeFrame: Week 8 post-FMT
measure: Endoscopic Response or Remission
timeFrame: Week 8 post-FMT
measure: Number of Treatment or Disease Related Adverse Events.
timeFrame: Week 0 Colonoscopy - Week 12 post-FMT, 6 months post-FMT, and 1 year post-FMT
Other outcomes:
Locations:
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Randy Longman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.