Bacteria & Inflammation in the Gut (BIG) Study (BIG)

August 16, 2017 updated by: NHS Greater Glasgow and Clyde

Gut Microbial Taxonomy and Metabolism in Paediatric Crohn's Disease During Exclusive and Supplementary Enteral Nutrition Using -Omics Technologies

Exclusive Enteral Nutrition (EEN) is the liquid diet given to children with active Crohn's Disease (CD). EEN has previously been shown to induce changes in major bacterial metabolites and dominant bacterial species which are more profound in children that clinically improve. This study aims to determine whether it is possible to maintain these bacterial changes with prolonged supplementary enteral nutrition (SEN) while returning to normal diet and if this can reduce risk of subsequent relapse for children with CD.

New technologies will allow measurement of a broad range of bacteria and metabolites, to test if the clinical response to EEN and changes in gut inflammation are associated with bacterial composition and chemical products; and if maintenance of changes using SEN reduces the risk of relapse over a 12 month period.

The study will aim to recruit all potential Crohn's disease children coming to a tertiary paediatric centre for colonoscopy. Once consented, an initial blood, urine and faecal sample will be requested along with 8 mucosal biopsies during the routine endoscopy session. If diagnosed with CD, and if the clinician prescribes treatment with EEN, an additional blood sample will be requested at the end of EEN, and 5 faecal and urine samples spread over 12 months; as well as some dietary information.

Samples will be collected from up to 42 children with CD and 42 age- and sex-matched healthy volunteers. Initial samples taken from children who were not diagnosed with CD will be compared with CD samples to look for potential metabolic disease markers. Characterisation of faecal bacteria and metabolites in both faeces and urine; as well as measurement of blood inflammatory biomarkers will be performed.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

The null hypothesis is that the clinical response to exclusive enteral nutrition (EEN) and reduction of colonic inflammatory markers are not associated with a characteristic bacterial taxonomy (composition) and metabolites (functionality); and that maintenance of any bacterial changes with supplementary enteral nutrition (SEN), while returning to habitual diet, does not reduce the risk of disease relapse.

The study design will build on previous work by looking at differences in both the gut bacteria (faecal and mucosal) and bacterial metabolic activity at different stages of disease activity. Changes in bacterial composition between disease groups will be examined; between Crohn's disease children on different treatments; and between different sites in the gut. Crohn's disease biomarkers in faeces and urine will also be assessed by analysing bacterial metabolites.

Up to a total of 42 children with Crohn's Disease will be recruited. 42 healthy children will also be recruited to provide a faecal and urine sample, to show the normal variety of gut bacteria and metabolites in healthy children for comparison.

Children who underwent colonoscopy but did not have Crohn's disease will be used as a comparison group to try and identify Crohn's disease bacterial signatures from faeces and urine, and as a non-Crohn's disease control group for comparison of mucosal biopsies.

Recruitment Three groups of children will participate in this study. A. Children undergoing endoscopic investigations (colonoscopy) for colonic inflammation including Crohn's disease [children who are found not to have Crohn's disease will not participate in the follow up aspect (during treatment with EEN) of this study].

B. Previously diagnosed patients with Crohn's disease due to start an 8 week standard course of treatment with EEN due to disease flare up.

C. Healthy children unrelated to Crohn's disease patients will be used as a control group.

Groups A and B: an initial blood, urine, faecal sample followed by 5 further faecal and urine samples over 12 months; and dietary information.

[Group A will also have 8 mucosal biopsies taken during routine endoscopy]. During treatment with EEN (clinical decision), an additional blood sample will be requested during routine blood sampling at start and end of treatment.

Group C: 1 urine and faecal sample will be requested.

All groups will have height, weight and grip strength measured at baseline. Participant receiving EEN will have this repeated 60 days after start of treatment and 60 days after end of treatment.

Detailed Methods Preliminary health check by means of a short health questionnaire - basic health information, age, any medication.

Mucosal samples: in newly diagnosed patients having a colonoscopy for diagnostic purposes, an additional 6 mucosal biopsy samples; 2 from the terminal ileum when possible, 2 from the proximal colon and 2 from the distal colon will be taken (14-16 are collected at normal colonoscopy). An additional 2 biopsy samples will also be collected from the duodenum during upper endoscopy.

Dietary information: habitual dietary intake and eating patterns assessed using validated Food Frequency Questionnaire (FFQ); a 5 step multiple pass 24 hour dietary recall questionnaire for data on actual diet at time of faecal and urine sampling.

EEN compliance (groups A&B only): completion of short EEN compliance questionnaire at 28 day and 56 day time points.

Medication and Disease History: information on disease activity, medication and medical history collected from medical notes.

Lab Assays Bacterial diversity: The gut bacterial diversity and composition from stool samples will be measured using molecular techniques such as quantitative polymerase chain reaction (PCR) from bacterial ribosomal DNA and next generation sequencing (metagenomics). These techniques will also be used to look at the composition of bacteria associated with mucosal tissue biopsies. Changes in overall gut bacteria composition using standard numerical indices will be measured across the 6 faecal samples collected over the 12 month period, as well as between groups.

Bacterial metabolism: A large number of different products from bacterial metabolism, such as short chain fatty acids, sulphide, and ammonia will be measured using a range of techniques including gas chromatography and gas chromatography mass spectrometry (GCMS) (metabolomics). Faecal pH, a marker of bacterial fermentation, will also be measured.

Disease markers: Other disease markers and metabolites such as faecal calprotectin, will be measured from faecal samples .

Study Type

Observational

Enrollment (Anticipated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United Kingdom
      • Glasgow, United Kingdom, G3 8SJ
      • Kilmarnock, United Kingdom, KA2 0BE
        • Recruiting
        • NHS Ayrshire & Arran - University Hospital Crosshouse
        • Contact:
          • Lawrence Armstrong
      • Larbert, United Kingdom, FK5 4WR
        • Not yet recruiting
        • NHS Forth Valley - Forth Valley Royal Hospital
        • Contact:
          • Ghassan Al-Hourani
      • Paisley, United Kingdom, PA2 9PN
        • Not yet recruiting
        • NHS Greater Glasgow & Clyde - Royal Alexandra Hospital
        • Contact:
          • Mohammed Iqbal
      • Wishaw, United Kingdom, ML2 0DP
        • Recruiting
        • NHS Lanarkshire - Wishaw General Hospital
        • Contact:
          • Caroline Delahunty

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 15 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Children with suspected or diagnosed Crohn's Disease attending a tertiary paediatric centre for treatment with exclusive enteral nutrition

Description

Inclusion Criteria:

  • Group A: children with suspected Crohn's Disease with scheduled colonoscopy
  • Group B: children with existing Crohn's Disease about to undergo treatment with EEN
  • Group C: healthy volunteers up to age 17 years willing to provide one urine and stool sample

Exclusion Criteria:

  • children who have taken antibiotics in the previous 4 weeks
  • children found not to have Crohn's Disease after colonoscopy will not be required to take any further part in the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
A) Newly diagnosed with Crohn's disease

Children undergoing endoscopic investigations (colonoscopy) for colonic inflammation including Crohn's disease [children who are found not to have Crohn's disease will not participate further].

[Intervention - clinical, not research decision - Exclusive Enteral Nutrition for 8 weeks; usually 330ml 6 times per day] per day
Other: Exclusive Enteral Nutrition (EEN)
8 week standard course of treatment with EEN
B) Existing diagnosis of Crohn's disease

Previously diagnosed patients with Crohn's disease due to start an 8 week standard course of treatment with EEN due to disease flare up.

[Intervention - clinical, not research decision - Exclusive Enteral Nutrition for 8 weeks; usually 330ml 6 times per day]
Other: Exclusive Enteral Nutrition (EEN)
8 week standard course of treatment with EEN
c) Healthy control group
Healthy children unrelated to Crohn's disease patients No intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bacterial metabolism
Time Frame: 12 months
Change in short chain fatty acid level following treatment with enteral nutrition
12 months
Gut bacterial composition
Time Frame: 12 months
Change in overall gut bacteria composition following treatment with enteral nutrition
12 months
Mucosal bacterial composition
Time Frame: 12 months
Change in overall bacteria composition in mucosal tissue biopsies
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Inflammatory markers
Time Frame: 12 months
Change in faecal calprotectin level before and after treatment with EEN
12 months
Dietary information
Time Frame: 12 months
Comparison of dietary composition between groups
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NHS Greater Glasgow and Clyde

Collaborators

University of Glasgow

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 18, 2014

Primary Completion (Anticipated)

July 1, 2018

Study Completion (Anticipated)

July 1, 2018

Study Registration Dates

First Submitted

January 14, 2015

First Submitted That Met QC Criteria

January 14, 2015

First Posted (Estimate)

January 19, 2015

Study Record Updates

Last Update Posted (Actual)

August 21, 2017

Last Update Submitted That Met QC Criteria

August 16, 2017

Last Verified

August 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GN14KH275

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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