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

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ClinicalTrials.gov Identifier: NCT02341248

Recruitment Status : Unknown

Verified August 2017 by NHS Greater Glasgow and Clyde.
Recruitment status was: Recruiting

First Posted : January 19, 2015

Last Update Posted : August 21, 2017

Sponsor:

Collaborator:

University of Glasgow

Information provided by (Responsible Party):

NHS Greater Glasgow and Clyde

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
Crohn Disease	Other: Exclusive Enteral Nutrition (EEN)

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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 Design

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Study Type :	Observational
Estimated Enrollment :	200 participants
Observational Model:	Case-Control
Time Perspective:	Prospective
Official Title:	Gut Microbial Taxonomy and Metabolism in Paediatric Crohn's Disease During Exclusive and Supplementary Enteral Nutrition Using -Omics Technologies
Actual Study Start Date :	July 18, 2014
Estimated Primary Completion Date :	July 2018
Estimated Study Completion Date :	July 2018

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Crohn disease

MedlinePlus related topics: Crohn's Disease

U.S. FDA Resources

Groups and Cohorts

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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Biospecimen Retention: Samples Without DNA

Blood, faecal, urine and mucosal samples retained.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	3 Years to 17 Years (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes
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

Criteria

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02341248

Contacts

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Contact: Clare M Clark, BSc MRes		c.clark.1@research.gla.ac.uk
Contact: Richard Russell, MBChB PhD		richardrussell@nhs.net

Locations

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United Kingdom
NHS Greater Glasgow & Clyde - Royal Hospital for Sick Children	Recruiting
Glasgow, United Kingdom, G3 8SJ
Contact: Clare M Clark, BSc MRes c.clark.1@research.gla.ac.uk
Contact: Richard Russell, MBChB PhD richardrussell@nhs.net
NHS Ayrshire & Arran - University Hospital Crosshouse	Recruiting
Kilmarnock, United Kingdom, KA2 0BE
Contact: Lawrence Armstrong
NHS Forth Valley - Forth Valley Royal Hospital	Not yet recruiting
Larbert, United Kingdom, FK5 4WR
Contact: Ghassan Al-Hourani
NHS Greater Glasgow & Clyde - Royal Alexandra Hospital	Not yet recruiting
Paisley, United Kingdom, PA2 9PN
Contact: Mohammed Iqbal
NHS Lanarkshire - Wishaw General Hospital	Recruiting
Wishaw, United Kingdom, ML2 0DP
Contact: Caroline Delahunty

Sponsors and Collaborators

NHS Greater Glasgow and Clyde

University of Glasgow

More Information

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Responsible Party:	NHS Greater Glasgow and Clyde
ClinicalTrials.gov Identifier:	NCT02341248
Other Study ID Numbers:	GN14KH275
First Posted:	January 19, 2015 Key Record Dates
Last Update Posted:	August 21, 2017
Last Verified:	August 2017

Keywords provided by NHS Greater Glasgow and Clyde:


Enteral Nutrition Pediatrics Microbiota Metabolomics

Additional relevant MeSH terms:

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Crohn Disease Inflammatory Bowel Diseases Gastroenteritis	Gastrointestinal Diseases Digestive System Diseases Intestinal Diseases

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