Clinical trial NCT02426567: The Impact of "Crohn's Disease-TReatment-with-EATing" Diet and Exclusive Enteral Nutrition on Healthy Gut Bacteria
Official title: An Exploratory Study on the Impact of a Food-based Restrictive Diet (Crohn's Disease-TReatment-with EATing/CD-TREAT Diet) and Liquid Exclusive Enteral Nutrition (EEN) on Healthy Gut Microbiota Composition and Metabolic Activity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Crohn's Disease
Dietary Modification
Keywords: Crohn's Disease
Exclusive Enteral Nutrition
Dietary Treatment
Gut microbiota
Lead sponsor: University of Glasgow
Sponsor class: OTHER
First posted: 2015-04-27
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: Current evidence suggests that the gut microbiota and dietary influences are as important as genetics in the aetiology of Crohn's disease (CD). We have recently shown that disease improvement, following treatment with Exclusive Enteral Nutrition (EEN), coincided with changes in the gut microbiota.

The main purposes of this study are: a) to explore whether the gut microbiota changes we observed in this previous study in children with CD during EEN are disease specific or not, and b) to develop a novel food-based diet (Crohn's Disease TReatment-with-EATing/CD-TREAT diet) which will induce changes to the metabolic activity and bacterial composition of the gut microbiota of healthy people, similar to those seen on EEN, the first-line treatment for active paediatric CD.

This study will produce high quality scientific evidence to move the CD-TREAT diet towards a preliminary clinical trial in patients with CD which is currently inappropriate and unethical to carry out in people with active CD undertaking contemporary medical treatment.

Detailed description: This study is a randomised, cross-over, dietary intervention trial. Healthy adult (\>18 y) participants from the community will be recruited by means of an advertisement leaflet and word of mouth. Eligible participants will be enrolled in the study. We will thank those subjects who have expressed an interest about the study but are not suitable to participate and we will explain to them why they need to be excluded. Those who are eligible and willing to participate will be asked to undertake two different experimental diets, for seven days each:

1. Exclusive Enteral Nutrition (EEN) which is the exclusive consumption of a milk-based proprietary dietary supplement (Modulen®, Nestle). This is a liquid based diet used for the management of children with active CD. Although this diet is used primary for clinical reasons it is food based and does not contain any drugs or non-food based pharmaceutical ingredients. It is available online and without prescription from pharmacist.
2. Crohn's Disease TReatment-with-EATing diet (CD-TREAT diet), an elimination customized diet which will consist of ordinary food and which will resemble the food/nutrient composition of EEN (e.g. fibre content, fatty acid composition) and considering evidence that implicates certain nutrients, and food ingredients (e.g. meat, sugar) in the aetiology and risk of relapse of CD. Diet will be created using the food group exchange methodology and will be analysed using Windiets® 2010.

Both diets will have the same energy content and will be isocaloric aiming to keep participants' weight stable during the study period. Their energy content will be tailored to participants' total energy expenditure and physical activity level calculated by the WHO set of equations. The order of the diets will be randomly allocated using an MS Excel command. In order to minimize fatigue with the diet but also to ensure that we will be able to detect changes in gut microbiota, experimental diets will be given for 7 days. This is based on recent evidence suggesting that dietary changes for 5 days induce reproducible alterations in gut microbiota composition and metabolism. Prior to the first diet intervention, participants will also record their dietary intake using a 7-day estimated food diary. Between the two interventions the participants will have to eat their habitual diet for two weeks and this will be a wash out period which aims to drive the gut microbiota back to baseline levels. The week prior to the initiation of the second intervention the participants will be asked to keep the same dietary pattern as they had the week prior to the first trial.

Detailed methods:

Preliminary Health Check: Participants will undertake a short health questionnaire including basic health information, age or any medication on the day of recruitment.

Anthropometry: All participants will have height and weight measured at baseline and only weight measured in each sample collection timepoint.

Diet compliance: Over the course of the two experimental diets we will monitor compliance by asking participants to complete a questionnaire. The questionnaire will ask if they felt the need to supplement the diets at any time with other foods or drinks. An interval call 2 days after each diet's initiation will also be used to increase participants' motivation and compliance on the diets.

Sample collection \& analysis: Fresh faecal and urine samples will be collected before and after each dietary intervention (4 times in total) to assess and compare the impact of these diets on gut microbiota composition and metabolic activity.

Lab Assays:

1. 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).
2. 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.

Power calculation: Fresh faecal and urine samples will be collected from 38 healthy participants at 4 time points. Based on our previous in vivo work in children with CD this would give us a power of 80% (p=0.05) to detect a mean concentration difference of 1.0 log (SD:1.5) in Faecalibacterium prausnitzii between their habitual diet and EEN diet or the CD-TREAT diet.

Eligibility criteria: Inclusion Criteria:

1. Healthy adult people
2. Normal weight (Body Mass Index: 18-25kg/m\^2)
3. Stable weight the past month

Exclusion Criteria:

1. Acute or chronic illness (defined as illness which requires regular visits to health services)
2. Positive or negative energy balance (recent weight gain or loss, ±2 Kg the past month)
3. History of gut surgery
4. Use of antibiotics or steroids the last 3 months

Primary outcomes:
measure: Gut Bacterial Composition
timeFrame: 12 months
measure: Gut Bacterial Metabolites
timeFrame: 12 months
Secondary outcomes:
measure: Dietary Intake
timeFrame: 12 months
Other outcomes:
Locations:
city: Glasgow
country: United Kingdom
facility: School of Medicine, University of Glasgow / New Lister Building, Glasgow Royal Infirmary
Study officials:
affiliation: University of Glasgow
name: Konstantinos Gerasimidis, BSc MSc PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Svolos V, Hansen R, Nichols B, Quince C, Ijaz UZ, Papadopoulou RT, Edwards CA, Watson D, Alghamdi A, Brejnrod A, Ansalone C, Duncan H, Gervais L, Tayler R, Salmond J, Bolognini D, Klopfleisch R, Gaya DR, Milling S, Russell RK, Gerasimidis K. Treatment of Active Crohn's Disease With an Ordinary Food-based Diet That Replicates Exclusive Enteral Nutrition. Gastroenterology. 2019 Apr;156(5):1354-1367.e6. doi: 10.1053/j.gastro.2018.12.002. Epub 2018 Dec 11.