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Trial registered on ANZCTR

Registration number

ACTRN12619000980134

Ethics application status

Approved

Date submitted

10/06/2019

Date registered

9/07/2019

Date last updated

19/04/2023

Date data sharing statement initially provided

9/07/2019

Type of registration

Prospectively registered

Titles & IDs

Public title

The role of a low emulsifier diet in treating Crohn’s disease - Study 1

Scientific title

The role of a low emulsifier diet in treating intestinal inflammation in patients with Crohn’s disease

Secondary ID [1]

None

Universal Trial Number (UTN)

U1111-1235-0246

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Crohn's disease

Condition category

Condition code

Inflammatory and Immune System

Autoimmune diseases

Oral and Gastrointestinal

Crohn's disease

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Study 1 in healthy subjects - in a cross-over design, healthy subjects will be provided 4 weeks of a low emulsifier diet and 4 weeks of a high emulsifier diet with a minimum of 3 weeks washout between the diets. A low emulsifier diet is developed by the researchers at The Alfred and based on knowledge of natural emulsifiers in addition to identified additive emulsifiers on packaged food. Researchers at The Alfred have a database of commercially available packaged food and their ingredients lists, which identify presence or absence of emulsifiers. A high emulsifier diet is matched nutritionally, but will use foods that contain emulsifiers. For example, two commercially available wholemeal breads that do and do not already contain emulsifiers will be provided during the dietary interventions. Unfortunately, quantification of emulsifiers in food is not possible, so 'high' and 'low' emulsifier diets will describe foods that have identifiable sources of emulsifiers or not. Research dietitians will be recruiting and arranging all food for the intervention is provided to participants. The diets will comprise of food cooked, individually portioned, vacuum-packed and frozen by our research chef. All food is readily available in supermarkets and already consumed by community. Adherence will be based on food diaries provided to participants and any returned food. On the last day of each of the intervention, the subjects will visit The Alfred Hospital and be provided a very high fat meal providing 56-60 g fat. The high fat meal will be similar to that used in previous studies investigating markers of intestinal injury and comprise of a sausage and cheese sandwich with hash browns and emulsifier-free peanut butter.

Intervention code [1]

Treatment: Other

Comparator / control treatment

Study 1 in healthy subjects - the comparator treatment will be a 4-week high emulsifier diet. All food will be provided to participants and the diets will comprise of food cooked, individually portioned, vacuum-packed and frozen by our research chef. All food is readily available in supermarkets and already consumed by community.

Control group

Active

Outcomes

Primary outcome [1]

Change in ratio of serum lipopolysaccharide binding protein to soluble CD14 as a marker of bacterial translocation in healthy subjects. Ratio of lipopolysaccharide binding protein to soluble CD14 is a well established marker of bacterial translocation as it reflects a major component of bacterial cell wall that can be quantitatively measured in plasma to show degree of microbial passage from the gut.

Timepoint [1]

After 4 weeks of each low and high emulsifier diets.

Secondary outcome [1]

Differences in gastrointestinal symptoms using a 100mm Visual Analogue Scale, which is a component of a validated survey for measuring symptoms in patients with irritable bowel syndrome.

Timepoint [1]

4 weeks of each low and high emulsifier diets

Secondary outcome [2]

Differences in faecal microbiota using 16S rRNA and shotgun metagenomic sequencing.

Timepoint [2]

4 weeks of each low and high emulsifier diets

Secondary outcome [3]

Differences in psychological health using the Hospital Anxiety and Depression Scale survey

Timepoint [3]

4 weeks of each low and high emulsifier diets

Secondary outcome [4]

Change in serum intestinal fatty acid binding protein-2 as markers of epithelial damage in healthy subjects.

Timepoint [4]

4 weeks of each low and high emulsifier diets

Secondary outcome [5]

Change in serum Syndecan-1 as a marker of epithelial damage in healthy subjects

Timepoint [5]

4 weeks each of low and high emulsifier diets

Secondary outcome [6]

Change in serum C-reactive protein as a marker of intestinal inflammation in healthy subjects.

Timepoint [6]

4 weeks each of low and high emulsifier diets

Secondary outcome [7]

Change in faecal calprotectin as a marker of intestinal inflammation in healthy subjects

Timepoint [7]

4 weeks each of low and high emulsifier diets

Eligibility

Key inclusion criteria

Healthy subjects - those that believe themselves to be healthy with no known gastrointestinal condition.

Minimum age

18 Years

Maximum age

60 Years

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key exclusion criteria

Study 1 - peanut allergy, recent use (previous 2 weeks) of probiotics, antibiotics, supplemental prebiotics, restrictive diets (including vegetarian) or any medication including complimentary and alternative medicines that might influence gut function or microbiota, coeliac disease and/or other gastrointestinal disease, malnutrition, and/or psychological illness, or inability to speak or read English or give informed consent.

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Allocation is not concealed

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s

Intervention assignment

Other

Other design features

Study 1 - cross-over in healthy subjects

Phase

Not Applicable

Type of endpoint/s

Efficacy

Statistical methods / analysis

Study 1 - Sample size calculations for this pilot trial are based on consensus opinion as there are no suitable studies for comparison. It is expected that n = 20 will provide suitable paired data in this study.

Per-protocol and intention-to-treat data will applied to all endpoints. Descriptive statistics will describe the outcome variables and data will be compared between the two cohorts using, for example, Wilcoxon rank sum test for continuous variables and Chi squared test for categorical variables.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

4/01/2021

Actual

3/02/2021

Date of last participant enrolment

Anticipated

Actual

20/09/2021

Date of last data collection

Anticipated

Actual

14/12/2021

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment postcode(s) [1]

3004 - Melbourne

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Crohn's & Colitis Foundation

Address [1]

733 Third Avenue, Suite 510
New York NY 10017

Country [1]

United States of America

Primary sponsor type

Hospital

Name

Alfred Health

Address

99 Commercial Rd
Melbourne VIC 3004

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Alfred Hospital Human Research Ethics Committee

Ethics committee address [1]

55 Commercial Rd
Melbourne VIC 3004

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

17/06/2019

Approval date [1]

01/08/2019

Ethics approval number [1]

Summary

Brief summary

The only dietary therapy to treat Crohn's disease (CD) is exclusive enteral nutrition (EEN), which has shown to heal the gut in a proportion of patients. EEN is a treatment that involves removing all food and replacing it with a nutritionally-complete liquid formula, usually for a six-week period. This observation shows that there is something in diet that is involved in driving or alleviating inflammation in CD. The exact way in which EEN works is unknown, so we cannot design a diet that may be used in place of EEN. One hypothesis that fits the observation of EEN treating CD is that certain dietary emulsifiers, often not found in enteral formulas, contribute to gut inflammation. Emulsifiers are commonly found in natural and manufactured foods and help to keep food stable by preventing the separation of water and oil. Animal and laboratory-based studies have shown that certain emulsifiers cause a leaky gut (i.e., they break down the intestinal barrier) and cause inflammation. This has never been investigated in humans. This proposal aims to address the main research question: Are dietary emulsifiers associated with breakdown of the intestinal barrier and inflammation? Research is underway to design low and high emulsifier diets for application in trials, including compilation of a database of manufactured foods. Based on the designed diets, we plan to conduct the first human dietary trial to examine the effects of a low emulsifier diet compared with a high emulsifier diet on highly sensitive markers of intestinal barrier function and inflammation in healthy subjects. All food will be provided to subjects in a cross-over design (i.e., subjects have both diets). At the end of each diet period, subjects will give blood, urine and faecal samples, which will be analysed for subtle markers of barrier function and inflammation that have already been established to represent a leaky gut in healthy people. This includes analysis bacterial translocation (passage of bacteria from gut to other parts of the body). Based on the outcomes of this trial, to determine duration and level of emulsifiers, a second trial providing low emulsifier or a safe comparator diet in patients with CD will be conducted.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Peter Gibson

Address

Alfred Hospital
Level 6 The Alfred Centre
99 Commercial Rd
Melbourne VIC 3004

Country

Australia

Phone

+61 3 99030640

Fax

Peter.Gibson@monash.edu

Contact person for public queries

Name

Emma Halmos

Address

Alfred Hospital
Level 6 The Alfred Centre
99 Commercial Rd
Melbourne VIC 3004

Country

Australia

Phone

+61 3 99030270

Fax

Emma.Halmos@monash.edu

Contact person for scientific queries

Name

Emma Halmos

Address

Alfred Hospital
Level 6 The Alfred Centre
99 Commercial Rd
Melbourne VIC 3004

Country

Australia

Phone

+61 3 99030270

Fax

Emma.Halmos@monash.edu

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

Only overall results of this study will be made publicly available in the form of published manuscripts.

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

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