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Trial registered on ANZCTR


Registration number
ACTRN12619000980134p
Ethics application status
Submitted, not yet approved
Date submitted
10/06/2019
Date registered
9/07/2019
Date last updated
9/07/2019
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] 298450 0
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 313196 0
Condition category
Condition code
Inflammatory and Immune System 311656 311656 0 0
Autoimmune diseases
Oral and Gastrointestinal 311763 311763 0 0
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] 314698 0
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] 320361 0
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] 320361 0
After 4 weeks of each low and high emulsifier diets.
Secondary outcome [1] 371349 0
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] 371349 0
4 weeks of each low and high emulsifier diets
Secondary outcome [2] 371639 0
Differences in faecal microbiota using 16S rRNA and shotgun metagenomic sequencing.
Timepoint [2] 371639 0
4 weeks of each low and high emulsifier diets
Secondary outcome [3] 371640 0
Differences in psychological health using the Hospital Anxiety and Depression Scale survey
Timepoint [3] 371640 0
4 weeks of each low and high emulsifier diets
Secondary outcome [4] 372190 0
Change in serum intestinal fatty acid binding protein-2 as markers of epithelial damage in healthy subjects.
Timepoint [4] 372190 0
4 weeks of each low and high emulsifier diets
Secondary outcome [5] 372191 0
Change in serum Syndecan-1 as a marker of epithelial damage in healthy subjects
Timepoint [5] 372191 0
4 weeks each of low and high emulsifier diets
Secondary outcome [6] 372192 0
Change in serum C-reactive protein as a marker of intestinal inflammation in healthy subjects.
Timepoint [6] 372192 0
4 weeks each of low and high emulsifier diets
Secondary outcome [7] 372193 0
Change in faecal calprotectin as a marker of intestinal inflammation in healthy subjects
Timepoint [7] 372193 0
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
Gender
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
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 26739 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 302998 0
Charities/Societies/Foundations
Name [1] 302998 0
Crohn's & Colitis Foundation
Address [1] 302998 0
733 Third Avenue, Suite 510
New York NY 10017
Country [1] 302998 0
United States of America
Primary sponsor type
Hospital
Name
Alfred Health
Address
99 Commercial Rd
Melbourne VIC 3004
Country
Australia
Secondary sponsor category [1] 302966 0
None
Name [1] 302966 0
Address [1] 302966 0
Country [1] 302966 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 303547 0
Alfred Hospital Human Research Ethics Committee
Ethics committee address [1] 303547 0
55 Commercial Rd
Melbourne VIC 3004
Ethics committee country [1] 303547 0
Australia
Date submitted for ethics approval [1] 303547 0
17/06/2019
Approval date [1] 303547 0
Ethics approval number [1] 303547 0

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 94042 0
Prof Peter Gibson
Address 94042 0
Alfred Hospital
Level 6 The Alfred Centre
99 Commercial Rd
Melbourne VIC 3004
Country 94042 0
Australia
Phone 94042 0
+61 3 99030640
Fax 94042 0
Email 94042 0
Peter.Gibson@monash.edu
Contact person for public queries
Name 94043 0
Dr Emma Halmos
Address 94043 0
Alfred Hospital
Level 6 The Alfred Centre
99 Commercial Rd
Melbourne VIC 3004
Country 94043 0
Australia
Phone 94043 0
+61 3 99030270
Fax 94043 0
Email 94043 0
Emma.Halmos@monash.edu
Contact person for scientific queries
Name 94044 0
Dr Emma Halmos
Address 94044 0
Alfred Hospital
Level 6 The Alfred Centre
99 Commercial Rd
Melbourne VIC 3004
Country 94044 0
Australia
Phone 94044 0
+61 3 99030270
Fax 94044 0
Email 94044 0
Emma.Halmos@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
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 other documents available
Summary results
No Results