Clinical trial NCT02291523: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Ulcerative Colitis
Keywords: Fecal transplant
Lead sponsor: Children's Hospital Los Angeles
Sponsor class: OTHER
First posted: 2014-11-14
Enrollment: 101
Sex: ALL
Minimum age (years): 7
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: Inclusion Criteria

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

Exclusion Criteria

* 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)
* Children with recent dose change of biologics (within 4 weeks), 5-ASA, steroids or immunomodulators (within 4 weeks)
* Allergy to or intolerance of mesalamine or 5-ASA products
* Any evidence of infectious colitis
* Concurrent infections that require anti-microbial therapy (such as abdominal abscess, pneumonia, etc...)
* Unable to give informed consent/assent
* Have received probiotic preparations ≤ 4 weeks prior to randomization
* Pregnancy and breast feeding in patient subjects of childbearing potential
* 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.

Primary outcomes:
measure: The primary endpoint is disease remission based on PUCAI scores (<10).
timeFrame: 12 Months
Secondary outcomes:
measure: Secondary endpoints will include change in mucosal inflammation reflected on laboratory studies.
timeFrame: 12 Months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
Study officials:
affiliation: Children Hospital Los Angeles
name: Sonia Michail, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.