The Effect of Therapeutic Fecal Transplant on the Gut Microbiome in Children With Ulcerative Colitis (FMT_UC)

• ClinicalTrials.gov Identifier: NCT02291523
• Recruitment Status: Active, not recruiting
• First Posted: November 14, 2014
• Last Update Posted: February 1, 2022
• Sponsor: Children's Hospital Los Angeles
• Information provided by (Responsible Party): Sonia Michail, MD, Children's Hospital Los Angeles

Tracking Information

• First Submitted Date: November 11, 2014
• First Posted Date: November 14, 2014
• Last Update Posted Date: February 1, 2022
• Study Start Date: November 2016
• Estimated Primary Completion Date: November 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 11, 2014)

The primary endpoint is disease remission based on PUCAI scores (<10). [ Time Frame: 12 Months ]

The primary outcome including results of disease activity, and safety measures.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 11, 2014)

Secondary endpoints will include change in mucosal inflammation reflected on laboratory studies. [ Time Frame: 12 Months ]

Secondary endpoints include changes in gut microbial diversity - determined by gut microbial genomics and proteomics, and outcome measures for mucosal inflammation and repair including laboratory testing such as the level for C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) as well as the stool calprotectin level.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The Effect of Therapeutic Fecal Transplant on the Gut Microbiome in Children With Ulcerative Colitis
• Official Title: The Effect of Therapeutic Fecal Transplant on the Gut Microbiome in Children With Ulcerative Colitis
• Brief Summary: Ninety Six patients with mild to moderate ulcerative colitis will be randomized to double blind, placebo controlled study. The safety and efficacy of the intervention will be closely monitored.
• Detailed Description: The enteric microbiota is now accepted as an important etiologic factor in the pathogenesis of human Inflammatory Bowel Disease (IBD) and immune-mediated chronic experimental intestinal inflammation, with ample data to implicate the microbiome as a main factor in the occurrence of IBD. This can be inferred from animals in germ-free environment which can protect from experimental colitis. In addition, increased gut permeability due to dysbiosis, is frequently seen in patients with IBD even in remission and, similarly, first degree relatives of IBD. Therefore, it is not surprising that therapeutic interventions aiming at modifying the gut microbiome would be of therapeutic benefit. Ulcerative colitis is a condition that is characterized by chronic inflammation of the colon. It is an important pediatric disease as 25% of all cases begin in childhood and its incidence is continuously on the rise. It is believed to be related to a genetically and environmentally-generated altered immune response to the enteric microbiome. Previous work in the PI's laboratory suggests that children harbor a unique gut microbial profile, which can predict therapeutic response. Therefore, modifying the gut microbiome may result in therapeutic benefit. However, attempts to modify the gut microbiome were largely unsuccessful until the advent of fecal transplant, which is a new approach in treating colitis. Fecal microbiota transplant (FMT) has been introduced several decades ago in an attempt to restore the gut microbial balance and it appears to be a more efficient method to effectively change and sustain the gut microbial composition. To date there have been a number of successful reports to suggest control of disease activity and in some cases cure of the disease. This study aims to further determine the safety and efficacy of FMT in treating children with ulcerative colitis
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Ulcerative Colitis

Intervention

Biological: Fecal Microbial Transplant

Fecal Transplant via Colonoscopy.

Other Name: FMT

Study Arms

• Sham Comparator: Patient Stool Transplant
  Arm 1 will get FMT (Fecal Microbial Transplant) placebo and high dose 5-ASA (Pentasa). The FMT is done through colonoscopy.
  Intervention: Biological: Fecal Microbial Transplant
• Active Comparator: Donor Stool Transplant
  Arm 2 will get FMT (Fecal Microbial Transplant) with Healthy Donor Stool and high dose 5-ASA (Pentasa). The FMT is done through colonoscopy.
  Intervention: Biological: Fecal Microbial Transplant

Publications *

• Michail S, Bultron G, Depaolo RW. Genetic variants associated with Crohn's disease. Appl Clin Genet. 2013 Jul 16;6:25-32. doi: 10.2147/TACG.S33966. Print 2013.
• Michail S, Durbin M, Turner D, Griffiths AM, Mack DR, Hyams J, Leleiko N, Kenche H, Stolfi A, Wine E. Alterations in the gut microbiome of children with severe ulcerative colitis. Inflamm Bowel Dis. 2012 Oct;18(10):1799-808. doi: 10.1002/ibd.22860. Epub 2011 Dec 14.
• Hyams JS, Lerer T, Mack D, Bousvaros A, Griffiths A, Rosh J, Otley A, Evans J, Stephens M, Kay M, Keljo D, Pfefferkorn M, Saeed S, Crandall W, Michail S, Kappelman MD, Grossman A, Samson C, Sudel B, Oliva-Hemker M, Leleiko N, Markowitz J; Pediatric Infl ammatory Bowel Disease Collaborative Research Group Registry. Outcome following thiopurine use in children with ulcerative colitis: a prospective multicenter registry study. Am J Gastroenterol. 2011 May;106(5):981-7. doi: 10.1038/ajg.2010.493. Epub 2011 Jan 11.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: July 6, 2016): 101
• Original Estimated Enrollment (submitted: November 11, 2014): 96
• Estimated Study Completion Date: November 2023
• Estimated Primary Completion Date: November 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria

1. Age: 7-21 who have been diagnosed with ulcerative colitis
2. Mild to moderate disease based on PUCAI with a score of 10-64
3. Need for colonoscopy

Exclusion Criteria

1. Children who are known to be resistant to steroid therapy, immunomodulators and biologics, or on a steroid dose greater than 0.5 mg/kg/day (maximum 20 mg)
2. Children with recent dose change of biologics (within 4 weeks), 5-ASA, steroids or immunomodulators (within 4 weeks)
3. Allergy to or intolerance of mesalamine or 5-ASA products
4. Any evidence of infectious colitis
5. Concurrent infections that require anti-microbial therapy (such as abdominal abscess, pneumonia, etc…)
6. Unable to give informed consent/assent
7. Have received probiotic preparations ≤ 4 weeks prior to randomization
8. Pregnancy and breast feeding in patient subjects of childbearing potential
9. Subjects with significant renal and liver dysfunction (creatinine > 2 mg/dl and direct bilirubin > 2 mg/dl), Subjects with congenital or acquired immunodeficiency, or who are immunosuppressed due to conditions other than ulcerative colitis (such as neoplastic disease or organ transplantation), have received or are receiving chemotherapy, or have been diagnosed with HIV.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 7 Years to 21 Years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02291523
• Other Study ID Numbers: CHLA-16-00050
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Sonia Michail, MD, Children's Hospital Los Angeles
• Original Responsible Party: Sonia Michail, MD, MemorialCare Health System, MD
• Current Study Sponsor: Children's Hospital Los Angeles
• Original Study Sponsor: MemorialCare Health System
• Collaborators: Not Provided

Investigators

• Principal Investigator: Sonia Michail, MD; Children Hospital Los Angeles

• PRS Account: Children's Hospital Los Angeles
• Verification Date: January 2022