Bacteria & Inflammation in the Gut (BIG) Study

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

Sponsors

Lead Sponsor: NHS Greater Glasgow and Clyde

Collaborator: University of Glasgow

Source NHS Greater Glasgow and Clyde
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.

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 .

Overall Status Unknown status
Start Date 2014-07-18
Completion Date 2018-07-01
Primary Completion Date 2018-07-01
Study Type Observational
Primary Outcome
Measure Time Frame
Bacterial metabolism 12 months
Gut bacterial composition 12 months
Mucosal bacterial composition 12 months
Secondary Outcome
Measure Time Frame
Inflammatory markers 12 months
Dietary information 12 months
Enrollment 200
Condition
Intervention

Intervention Type: Other

Intervention Name: Exclusive Enteral Nutrition (EEN)

Description: 8 week standard course of treatment with EEN

Eligibility

Sampling Method:

Non-Probability Sample

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

Gender:

All

Minimum Age:

3 Years

Maximum Age:

17 Years

Healthy Volunteers:

Accepts Healthy Volunteers

Overall Contact

Last Name: Clare M Clark, BSc MRes

Email: [email protected]

Location
Facility: Status: Contact: Contact Backup:
NHS Greater Glasgow & Clyde - Royal Hospital for Sick Children | Glasgow, G3 8SJ, United Kingdom Recruiting Clare M Clark, BSc MRes [email protected]
NHS Ayrshire & Arran - University Hospital Crosshouse | Kilmarnock, KA2 0BE, United Kingdom Recruiting Lawrence Armstrong
NHS Forth Valley - Forth Valley Royal Hospital | Larbert, FK5 4WR, United Kingdom Not yet recruiting Ghassan Al-Hourani
NHS Greater Glasgow & Clyde - Royal Alexandra Hospital | Paisley, PA2 9PN, United Kingdom Not yet recruiting Mohammed Iqbal
NHS Lanarkshire - Wishaw General Hospital | Wishaw, ML2 0DP, United Kingdom Recruiting Caroline Delahunty
Location Countries

United Kingdom

Verification Date

2017-08-01

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Arm Group

Label: A) Newly diagnosed with Crohn's disease

Description: 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

Label: B) Existing diagnosis of Crohn's disease

Description: 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]

Label: c) Healthy control group

Description: Healthy children unrelated to Crohn's disease patients No intervention

Acronym BIG
Study Design Info

Observational Model: Case-Control

Time Perspective: Prospective

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 [email protected]. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Research News