Effects of Exclusive Enteral Nutrition on the Microbiome in Pediatric Inflammatory Bowel Disease

Inflammatory Bowel Diseases Clinical Trial

Official title:

The Role of Exclusive Enteral Nutrition in the Pediatric Inflammatory Bowel Disease Microbiome: a Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02521064
• Other study ID #: McmasterCH - 15-365
• Status: Completed
• Phase: N/A
• First received: July 29, 2015
• Last updated: April 30, 2017
• Start date: July 2015
• Est. completion date: August 2016

Study information

• Verified date: April 2017
• Source: McMaster Children's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: August 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Inflammatory Bowel Diseases
• Intestinal Diseases

Intervention

Dietary Supplement:
• Exclusive Enteral Nutrition (EEN)
Patients will be treated with 8 weeks of Exclusive Enteral Nutrition (EEN). Patients will continue to receive usual medical care, and concurrent IBD treatments will be permitted.

Drug:
• Prednisone
Patients will be treated with 8 weeks of prednisone (corticosteroid). Patients will continue to receive usual medical care, and concurrent IBD treatments will be permitted.

Locations

Country	Name	City	State
Canada	McMaster Children's Hospital	Hamilton	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
McMaster Children's Hospital	Canadian Association of Gastroenterology

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility: Participant recruitment rate	Number of participants recruited per month	Entirety of study (1 year)
Primary	Feasibility: Participant retention rate	Number of participants enrolled who did not complete the study	Entirety of study (1 year)
Primary	Feasibility: Participant compliance with intervention: treatment (EEN or corticosteroids)	Number of participants who completed full treatment duration	Entirety of study (1 year)
Primary	Feasibility: Participant compliance with intervention: bloodwork, stool and urine sampling	Number of blood, stool and urine sample collections per participant	Entirety of study (1 year)
Primary	Feasibility: Participant compliance with weekly interviews	Number of weekly interviews completed per participant; Interviews discussing: a) disease assessment (Pediatric Ulcerative Colitis Activity Index [PUCAI]/Pediatric Crohn's Disease Activity Index [PCDAI] scores), and b) quality of life (health-related quality of life questionnaire)	Entirety of study (1 year)
Primary	Feasibility: Rate of adverse events in patients with ulcerative colitis receiving EEN	Record of all adverse events	Entirety of study (1 year)
Secondary	Changes in microbiome (composite measure)	Changes in microbial community structure in patients receiving EEN versus corticosteroid induction therapy. Multiple indices of alpha and beta diversity will comprise composite assessment of microbiome change.	Entirety of study (1 year)
Secondary	Clinical remission (composite measure)	Effects of EEN therapy on induction of clinical remission in pediatric UC versus CD. Composite assessment consisting of: 8 weeks: PUCAI ? =20; PCDAI ? =15, decrease in serum ESR, CRP, and fecal calprotectin; 12 weeks: PUCAI <10; PCDAI <15, Normalization of serum ESR, CRP and fecal calprotectin)	Entirety of study (1 year)
Secondary	Patient satisfaction and quality of life	Patient satisfaction with the treatment (satisfaction validated questionnaire)	Entirety of study (1 year)
Secondary	Patient quality of life	Quality of life during induction therapy (quality of life validated questionnaire)	Entirety of study (1 year)