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Trial registered on ANZCTR


Registration number
ACTRN12619001099112
Ethics application status
Approved
Date submitted
18/06/2019
Date registered
9/08/2019
Date last updated
4/09/2019
Date data sharing statement initially provided
9/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The role of a low emulsifier diet in treating Crohn’s disease - Study 2
Scientific title
The role of a low emulsifier diet in treating intestinal inflammation in patients with Crohn’s disease
Secondary ID [1] 298523 0
None
Universal Trial Number (UTN)
U1111-1235-5782
Trial acronym
Linked study record
U1111-1235-0246
This study is a follow-up study of the above UTN study, which investigates dietary emulsifiers in healthy subjects. The results of study U111-1235-0246 will guide how a low emulsifier and controlled diet will be applied in patients with Crohn's disease, as this study describes.

Health condition
Health condition(s) or problem(s) studied:
Crohn's disease 313331 0
Condition category
Condition code
Inflammatory and Immune System 311769 311769 0 0
Autoimmune diseases
Oral and Gastrointestinal 311770 311770 0 0
Crohn's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Study 2 in patients with mild Crohn's disease - subjects will be randomised to either a low emulsifier diet, hypothesised to treat disease activity, or a controlled diet for 4 weeks. The controlled diet will be either the subjects' usual diet or a high emulsifier diet. The 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. The choice of controlled diet will depend on the results of Study 1 (UTN - U1111-1235-0246). 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. Unfortunately, quantification of emulsifiers in food is not possible, so a low emulsifier diet describes foods that have no identifiable sources of emulsifiers on ingredients lists. 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. Examples of meals may include a risotto or pasta dish. 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.

If Study 1 indicates that a high emulsifier diet induces intestinal inflammation above baseline, the subjects' usual diet will be used as the controlled diet.
Intervention code [1] 314770 0
Treatment: Other
Comparator / control treatment
Study 2 in patients with mild Crohn's disease - the controlled diet will be either the subjects' usual diet or a provided high emulsifier diet, depending on the results of Study 1. If Study 1 indicates that a high emulsifier diet induces intestinal inflammation above baseline, the subjects' usual diet will be used to ensure safety. This will be the subjects' usual diet, meaning their normal, unaltered diet. If Study 1 indicates that a high emulsifier diet is similar to baseline results (indicating no additional negative impact above a normal diet), a designed high emulsifier diet will be the controlled diet. A high emulsifier diet is matched nutritionally to the low emulsifier diet, 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.
Control group
Active

Outcomes
Primary outcome [1] 320453 0
Change in faecal calprotectin as a marker of intestinal inflammation.
Timepoint [1] 320453 0
After 4 weeks of either low emulsifier or controlled diet.
Primary outcome [2] 320454 0
Change in intestinal wall thickness on intestinal ultrasound as a marker of intestinal inflammation in patients with Crohn's disease.
Timepoint [2] 320454 0
After 4 weeks of either low emulsifier or controlled diet.
Primary outcome [3] 320455 0
Change in Harvey-Bradshaw Crohn's Disease Activity Index survey as a marker of active disease.
Timepoint [3] 320455 0
After 4 weeks of either low emulsifier or controlled diet.
Secondary outcome [1] 371645 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] 371645 0
After 4 weeks of low emulsifier or controlled diet.
Secondary outcome [2] 371646 0
Differences in faecal microbiota using 16S rRNA and shotgun metagenomic sequencing.
Timepoint [2] 371646 0
After 4 weeks of either low emulsifier or controlled diet.
Secondary outcome [3] 371647 0
Differences in psychological health using the Hospital Anxiety and Depression Scale survey
Timepoint [3] 371647 0
After 4 weeks of a low emulsifier or controlled diet.
Secondary outcome [4] 371648 0
Change in serum C-reactive protein as a marker of inflammation.
Timepoint [4] 371648 0
After 4 weeks of a low emulsifier or controlled diet.
Secondary outcome [5] 372199 0
Change in ratio of serum lipopolysaccharide binding protein and soluble CD14 as a markder of bacterial translocation in patients with Crohn's disease.
Timepoint [5] 372199 0
After 4 weeks of a low emulsifier or controlled diet.

Eligibility
Key inclusion criteria
Study 2 - patients with mild Crohn's disease on stable medical therapy for at least 2 months. Severity of disease activity will be based on elevated disease activity index (Harvey Bradshaw Index) and/or elevated faecal calprotectin.
Minimum age
18 Years
Maximum age
60 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Study 2 - 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, 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
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Study 2 - As there are no suitable studies for comparison, a sample size of 40 subjects (20 each dietary group) is proposed based on consensus option, but results from Study 1 will help inform power calculations for the CD cohort. A limited interim analysis after 20 patients will be performed.
Both 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 hospital [1] 14011 0
The Alfred - Prahran
Recruitment postcode(s) [1] 26796 0
3004 - Prahran

Funding & Sponsors
Funding source category [1] 303069 0
Charities/Societies/Foundations
Name [1] 303069 0
Crohn's & Colitis Foundation
Address [1] 303069 0
733 Third Avenue, Suite 510
New York NY 10017
Country [1] 303069 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] 303052 0
None
Name [1] 303052 0
Address [1] 303052 0
Country [1] 303052 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303617 0
Alfred Hospital Human Research Ethics Committee
Ethics committee address [1] 303617 0
55 Commercial Rd
Melbourne VIC 3004
Ethics committee country [1] 303617 0
Australia
Date submitted for ethics approval [1] 303617 0
17/06/2019
Approval date [1] 303617 0
01/08/2019
Ethics approval number [1] 303617 0

Summary
Brief summary
It is hypothesised that removal of dietary emulsifiers, which can help mix oil and water together, will treat gut inflammation seen in Crohn's disease. This proposal aims to address the main research question: Are dietary emulsifiers associated with breakdown of the intestinal barrier and inflammation? We have designed a low and high emulsifier diet and we plan to conduct a human dietary trial to examine the effects of a low emulsifier diet in patients with Crohn's disease. Crohn's disease patients will receive either a low emulsifier or controlled diet for 4 weeks. At the end of diet period, subjects will give blood, urine and faecal samples, which will be analysed for markers of inflammation.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 94278 0
Prof Peter Gibson
Address 94278 0
Alfred Hospital
Level 6 The Alfred Centre
99 Commercial Rd
Melbourne VIC 3004
Country 94278 0
Australia
Phone 94278 0
+61 3 99030640
Fax 94278 0
Email 94278 0
Peter.Gibson@monash.edu
Contact person for public queries
Name 94279 0
Dr Emma Halmos
Address 94279 0
Alfred Hospital
Level 6 The Alfred Centre
99 Commercial Rd
Melbourne VIC 3004
Country 94279 0
Australia
Phone 94279 0
+61 3 99030270
Fax 94279 0
Email 94279 0
Emma.Halmos@monash.edu
Contact person for scientific queries
Name 94280 0
Dr Emma Halmos
Address 94280 0
Alfred Hospital
Level 6 The Alfred Centre
99 Commercial Rd
Melbourne VIC 3004
Country 94280 0
Australia
Phone 94280 0
+61 3 99030270
Fax 94280 0
Email 94280 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