Clinical trial NCT02521064: Effects of Exclusive Enteral Nutrition on the Microbiome in Pediatric Inflammatory Bowel Disease
Official title: The Role of Exclusive Enteral Nutrition in the Pediatric Inflammatory Bowel Disease Microbiome: a Pilot Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Inflammatory Bowel Diseases
Keywords: IBD
enteral nutrition
corticosteroids
Lead sponsor: McMaster Children's Hospital
Sponsor class: OTHER
Collaborators: name: Canadian Association of Gastroenterology
First posted: 2015-08-13
Enrollment: 31
Sex: ALL
Minimum age (years): 5
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Pediatric patients (\<18yo) being followed and managed through the McMaster Children's Hospital's Division of Pediatric Gastroenterology. Patients are diagnosed with Crohn's Disease, Ulcerative Colitis, or Inflammatory Bowel Disease-Unclassified.

Brief summary: Children with Crohn's disease can be effectively treated by remaining on a single-formula diet for 8 continuous weeks. This dietary therapy is known as "exclusive enteral nutrition" (EEN). It is just as effective as steroid treatment, which is what's traditionally used for the initial treatment of Crohn's disease. It is not clear why EEN is an effective treated. One possibility is that it changes the bacteria in our intestines, which allows the intestine to heal. It is also unclear whether EEN can be used to treat ulcerative colitis, a disease that is very similar to Crohn's disease. The purpose of our research project is to determine whether EEN can be used to treat ulcerative colitis, and understand how the intestinal bacteria changes while on EEN. Investigators will compare the results to patients who have either Crohn's disease or ulcerative colitis, and are receiving standard treatment for their disease (steroids). This is a pilot study, meaning that the goal of this study is to determine whether a larger study is feasible. Investigators will measure patient recruitment rates, whether patients are able to perform the treatment as requested, whether there are any safety concerns, and whether investigators are able to collect the bloodwork and stool samples without difficulty.

Detailed description: Exclusive enteral nutrition (EEN) is an effective induction therapy in pediatric Crohn's disease (CD). Compared to corticosteroids, EEN has equivalent rates of clinical remission and significantly higher rates of mucosal healing and weight gain. There is a paucity of literature on the role of EEN in ulcerative colitis (UC). Some have postulated that colonic disease will not respond to EEN, yet two series found no difference in rates of clinical remission between small intestinal and colonic CD. The mechanisms underlying the effectiveness of enteral nutrition in colitis remain unclear. A microbiome-mediated pathogenesis is possible. Two studies have shown how EEN produces profound changes in microbial community structure within as little as 24 hours. These changes correlated with improved disease activity scores. Active inflammatory bowel disease also carries distinct microbial signatures. Baseline differences in taxonomy between IBD phenotypes may account for differences in EEN efficacy between CD and UC.

The purpose of the pilot study is to investigate if EEN can be used for induction of remission of ulcerative colitis, and compare its usage to a) corticosteroids for UC and b) EEN or corticosteroids for Crohn's disease. The goal is to eventually characterize the clinical, biochemical and microbial changes that occur with each. However, given that EEN is a challenging commitment, as a sole source of nutrition for 8 weeks, investigators first have to evaluate feasibility in terms of participant recruitment, compliance and safety of this treatment. Both EEN and corticosteroid treatment require proper compliance to be effective, which can be a significant burden for the patient and his/her family. Investigators will therefore also determine satisfaction with the induction therapies and effect on quality of life. Further, since frequent follow up is being requested, investigators need to assess recruitment and retention rates, as well as compliance with completing bloodwork and providing stool samples. Investigators hypothesize that these induction therapies will be both feasible and safe. However, it is anticipated that, while patients will be satisfied with the treatment, it may have a significant impact on quality of life during those 8 week.

Eligibility criteria: Inclusion Criteria:

* Children 5-18 years old who have been diagnosed with IBD (confirmed by endoscopy, histology and radiography), and are followed by McMaster Children's Hospital's Division of Pediatric Gastroenterology and Nutrition.
* Patients requiring induction therapy
* Patients already taking 5-aminosalicylic acid (5-ASA) azathioprine, 6-mercaptopurine or anti-TNF (tissue necrosis factor) therapy (e.g. infliximab)

Exclusion Criteria:

* Patients who are in remission (on maintenance therapy).
* Patients who receive new medical therapies (e.g. antibiotics, probiotics) during the study period

Primary outcomes:
measure: Feasibility: Participant recruitment rate
timeFrame: Entirety of study (1 year)
measure: Feasibility: Participant retention rate
timeFrame: Entirety of study (1 year)
measure: Feasibility: Participant compliance with intervention: treatment (EEN or corticosteroids)
timeFrame: Entirety of study (1 year)
measure: Feasibility: Participant compliance with intervention: bloodwork, stool and urine sampling
timeFrame: Entirety of study (1 year)
measure: Feasibility: Participant compliance with weekly interviews
timeFrame: Entirety of study (1 year)
measure: Feasibility: Rate of adverse events in patients with ulcerative colitis receiving EEN
timeFrame: Entirety of study (1 year)
Secondary outcomes:
measure: Changes in microbiome (composite measure)
timeFrame: Entirety of study (1 year)
measure: Clinical remission (composite measure)
timeFrame: Entirety of study (1 year)
measure: Patient satisfaction and quality of life
timeFrame: Entirety of study (1 year)
measure: Patient quality of life
timeFrame: Entirety of study (1 year)
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: McMaster Children's Hospital
state: Ontario
Study officials:
affiliation: McMaster University
name: Nikhil Pai, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References: