Bacteria & Inflammation in the Gut (BIG) Study

NCT ID: NCT02341248

Last Updated: 2017-08-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

200 participants

Study Classification

OBSERVATIONAL

Study Start Date

2014-07-18

Study Completion Date

2018-07-31

Brief Summary

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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

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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 .

Conditions

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Crohn Disease

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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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

Exclusive Enteral Nutrition (EEN)

Intervention Type OTHER

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.

\[Intervention - clinical, not research decision - Exclusive Enteral Nutrition for 8 weeks; usually 330ml 6 times per day\]

Exclusive Enteral Nutrition (EEN)

Intervention Type OTHER

8 week standard course of treatment with EEN

c) Healthy control group

Healthy children unrelated to Crohn's disease patients No intervention

No interventions assigned to this group

Interventions

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Exclusive Enteral Nutrition (EEN)

8 week standard course of treatment with EEN

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

3 Years

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Glasgow

OTHER

Sponsor Role collaborator

NHS Greater Glasgow and Clyde

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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NHS Greater Glasgow & Clyde - Royal Hospital for Sick Children

Glasgow, , United Kingdom

Site Status RECRUITING

NHS Ayrshire & Arran - University Hospital Crosshouse

Kilmarnock, , United Kingdom

Site Status RECRUITING

NHS Forth Valley - Forth Valley Royal Hospital

Larbert, , United Kingdom

Site Status NOT_YET_RECRUITING

NHS Greater Glasgow & Clyde - Royal Alexandra Hospital

Paisley, , United Kingdom

Site Status NOT_YET_RECRUITING

NHS Lanarkshire - Wishaw General Hospital

Wishaw, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Clare M Clark, BSc MRes

Role: CONTACT

Richard Russell, MBChB PhD

Role: CONTACT

Facility Contacts

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Clare M Clark, BSc MRes

Role: primary

Richard Russell, MBChB PhD

Role: backup

Lawrence Armstrong

Role: primary

Ghassan Al-Hourani

Role: primary

Mohammed Iqbal

Role: primary

Caroline Delahunty

Role: primary

References

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Logan M, MacKinder M, Clark CM, Kountouri A, Jere M, Ijaz UZ, Hansen R, McGrogan P, Russell RK, Gerasimidis K. Intestinal fatty acid binding protein is a disease biomarker in paediatric coeliac disease and Crohn's disease. BMC Gastroenterol. 2022 May 23;22(1):260. doi: 10.1186/s12876-022-02334-6.

Reference Type DERIVED
PMID: 35606704 (View on PubMed)

Gkikas K, Logan M, Nichols B, Ijaz UZ, Clark CM, Svolos V, Gervais L, Duncan H, Garrick V, Curtis L, Buchanan E, Cardigan T, Armstrong L, Delahunty C, Flynn DM, Barclay AR, Tayler R, Milling S, Hansen R, Russell RK, Gerasimidis K. Dietary triggers of gut inflammation following exclusive enteral nutrition in children with Crohn's disease: a pilot study. BMC Gastroenterol. 2021 Dec 3;21(1):454. doi: 10.1186/s12876-021-02029-4.

Reference Type DERIVED
PMID: 34861829 (View on PubMed)

Other Identifiers

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GN14KH275

Identifier Type: -

Identifier Source: org_study_id

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