Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000568819
Ethics application status
Approved
Date submitted
19/03/2021
Date registered
14/05/2021
Date last updated
23/03/2023
Date data sharing statement initially provided
14/05/2021
Date results information initially provided
23/03/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of Exclusive Enteral Nutrition (EEN) in healthy participants
Scientific title
The impact of Exclusive Enteral Nutrition on intestinal physiology and microbiology in healthy controls
Secondary ID [1] 303669 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Crohn's disease 321067 0
Condition category
Condition code
Inflammatory and Immune System 318873 318873 0 0
Autoimmune diseases
Diet and Nutrition 318874 318874 0 0
Other diet and nutrition disorders
Oral and Gastrointestinal 319348 319348 0 0
Crohn's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Exclusive enteral nutrition (EEN) involves the provision of specialised liquid nutrition formula (Nutricia, Fortisip), excluding all table foods and fluids with the exception of water, to patient's with Crohn's Disease to induce remission. In this study we will be giving EEN to healthy participants for a period of 3 weeks to assess changes this has on intestinal physiology and microbiology. Frequency of administration will be dependent on individual participant's estimated nutrition requirements, however likely to be 5-8 200ml bottles/day (spread across the day based on participant preference).
The EEN regime will be prescribed by a dietitian with >8 years experience. Estimated nutrition requirements will be calculated (energy and protein) by the dietitian and amount of formula prescribed will meet these estimated requirements.
All formula will be provided to the participants at no cost.
Participants progress with EEN will be reviewed weekly by the dietitian (face to face or via phone) and adjusted accordingly based on tolerance, weight fluctuations and satiety
Adherence will be assessed by direct questioning, participant maintained diaries and amount of formula used.
Study visits whilst on EEN (to collect serum, urine and faecal samples) will occur at the Alfred Hospital, Monash University building, 55 Commercial Rd, Melbourne VIC
To safely induce intestinal stress in healthy subjects, participants will be administered a corticotrophin releasing hormone injection by a medical professional prior to commencing EEN and again after 3 weeks on EEN. Urine and blood samples will be taken following this injection.
Intervention code [1] 319969 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 326908 0
Changes in bacterial translocation indicated by ratio of serum lipopolysaccharide (LPS) binding protein to soluble CD14 (sCD14)
Timepoint [1] 326908 0
Prior to commencement of EEN and on completion of 3 weeks of EEN
Secondary outcome [1] 393063 0
Intestinal permeability measured by dual sugar absorption test
Timepoint [1] 393063 0
Prior to commencement of EEN and on completion of 3 weeks of EEN
Secondary outcome [2] 393064 0
Systemic inflammation by measuring serum highly sensitive C-reactive protein
Timepoint [2] 393064 0
Prior to commencement of EEN and on completion of 3 weeks of EEN
Secondary outcome [3] 393065 0
Intestinal inflammation measured by faecal calprotectin
Timepoint [3] 393065 0
Prior to commencement of EEN and on completion of 3 weeks of EEN
Secondary outcome [4] 393066 0
Epithelial injury by measuring serum intestinal Fatty Acid Binding Protein-1, syndecan-1
Timepoint [4] 393066 0
Prior to commencement of EEN and on completion of 3 weeks of EEN
Secondary outcome [5] 393067 0
Regional gastrointestinal transit times measured using the ‘Smart Pill’ and Atmo Capsule
Timepoint [5] 393067 0
Prior to commencement of EEN and on completion of 3 weeks of EEN
Secondary outcome [6] 393068 0
Luminal pH profiles measured using the ‘Smart Pill’
Timepoint [6] 393068 0
Prior to commencement of EEN and on completion of 3 weeks of EEN
Secondary outcome [7] 393069 0
Luminal gas profiles using the Atmos Gas capsule
Timepoint [7] 393069 0
Prior to commencement of EEN and on completion of 3 weeks of EEN
Secondary outcome [8] 393070 0
Changes in state and trait anxiety using Spielberger State Trait Personality Inventory (STPI)
Timepoint [8] 393070 0
Prior to commencement of EEN and on completion of 3 weeks of EEN
Secondary outcome [9] 393071 0
Individual VOCs measured in faecal samples using gas chromatography/mass spectroscopy
Timepoint [9] 393071 0
Prior to commencement of EEN and on completion of 3 weeks of EEN
Secondary outcome [10] 394264 0
Volatile Organic Compound (VOC) profiles using the Atmos Gas capsule
Timepoint [10] 394264 0
Prior to commencement of EEN and on completion of 3 weeks EEN
Secondary outcome [11] 394265 0
Faecal VOC patterns measured in faecal samples measured using gas chromatography/mass spectroscopy
Timepoint [11] 394265 0
Prior to commencement of EEN and on completion of 3 weeks of EEN
Secondary outcome [12] 394267 0
Changes in state and trait depression using Spielberger State Trait Personality Inventory (STPI)
Timepoint [12] 394267 0
Prior to commencement of EEN and on completion of 3 weeks of EEN

Eligibility
Key inclusion criteria
18-60 years of age in good health
English speaking to provide informed consent
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• Use of antibiotics, probiotics or supplementary prebiotics in previous 2 weeks
• Family history of IBD
• History of gastrointestinal conditions
• History of eating disorder
• Recent weight changes (>5% within past 1 month)
• Body Mass Index (BMI) <18.5 or >30
• Restrictive diets with potential major alteration to nutrient balance (e.g., vegan, paleo)
• Current psychological illness
• Smoker
• Taking medication known to alter intestinal barrier function
• Pregnant or breast feeding

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size
As this is a pilot study with no data upon which to power, an initial cohort of 10 subjects will be studied.

Data analysis plan
Data analysis will be undertaken using the Statistical Package for Social Sciences (SPSS), version 20, (SPSS, Chicago, Inc):
• Descriptive statistics
• Statistical significance will be taken as p < 0.05.

Both per-protocol and intention-to-treat data will applied to all endpoints. Descriptive statistics will describe the outcome variables and baseline data will compared with that after intervention 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
1/06/2021
Actual
1/09/2021
Date of last participant enrolment
Anticipated
1/06/2022
Actual
1/06/2022
Date of last data collection
Anticipated
30/06/2022
Actual
30/06/2022
Sample size
Target
10
Accrual to date
Final
10
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 18949 0
The Alfred - Melbourne
Recruitment postcode(s) [1] 33457 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 308088 0
University
Name [1] 308088 0
Monash University
Country [1] 308088 0
Australia
Primary sponsor type
Individual
Name
Professor Peter Gibson
Address
The Alfred Centre, Central Clinical School, Level 5
99 Commercial Rd, Melbourne VIC 3004
Country
Australia
Secondary sponsor category [1] 308829 0
None
Name [1] 308829 0
Address [1] 308829 0
Country [1] 308829 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308074 0
Monash University Human Research Ethics Committee
Ethics committee address [1] 308074 0
Wellington Rd, Clayton VIC 3800
Ethics committee country [1] 308074 0
Australia
Date submitted for ethics approval [1] 308074 0
23/02/2021
Approval date [1] 308074 0
09/07/2021
Ethics approval number [1] 308074 0

Summary
Brief summary
Exclusive Enteral Nutrition (EEN) reduces inflammation and allows complete gut healing in up to 80% of people with Crohn’s Disease (CD). EEN involves removing all food and replacing it with a liquid containing all essential nutrients for 6-8 weeks. This treatment is superior to steroids in treating inflammation and is being increasingly used across Australasia as first-line therapy, particularly in children. Despite EEN having been shown to be effective in numerous studies, the ways in which it works to reduce inflammation is still unknown. To date, hypotheses as to why it may have this effect include by altering the gut microbiota, by removing potentially harmful components in the diet, by delivering nutrition directly to the gut and by allowing the gut to rest. This study seeks to address these hypotheses by assessing how EEN works. The best way to assess how a therapy works to treat disease is to examine its impact in a model of ‘normal’ and ‘diseased’ gut. This study intends to use a CD model of safely inducing intestinal stress in healthy subjects and measuring markers of subtle intestinal injury before and after they receive EEN for three weeks. By gaining a better understanding of how EEN works, we may be able to better utilise this therapy, contribute to the understanding of the relationship between diet and CD which may then assist in the development of more specific dietary therapy.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 109438 0
Prof Peter Gibson
Address 109438 0
Alfred Centre, Central Clinical School, Level 5
99 Commercial Rd, Melbourne VIC 3004
Country 109438 0
Australia
Phone 109438 0
+61 39076 3325
Fax 109438 0
Email 109438 0
[email protected]
Contact person for public queries
Name 109439 0
Ms Sarah Melton
Address 109439 0
Alfred Centre, Central Clinical School, Level 5
99 Commercial Rd, Melbourne VIC 3004
Country 109439 0
Australia
Phone 109439 0
+61 431881263
Fax 109439 0
Email 109439 0
[email protected]
Contact person for scientific queries
Name 109440 0
Ms Sarah Melton
Address 109440 0
Alfred Centre, Central Clinical School, Level 5
99 Commercial Rd, Melbourne VIC 3004
Country 109440 0
Australia
Phone 109440 0
+61 431881263
Fax 109440 0
Email 109440 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual participant data not to be shared publicly due to confidentially


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.