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Trial registered on ANZCTR


Registration number
ACTRN12622000449730
Ethics application status
Approved
Date submitted
25/02/2022
Date registered
22/03/2022
Date last updated
3/03/2023
Date data sharing statement initially provided
22/03/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Treating adult Crohn's disease with exclusive enteral nutrition using a protocolised approach
Scientific title
Implementation of a protocol optimised for managing exclusive enteral nutrition therapy in adults with Crohn’s Disease: A pilot effectiveness-implementation study
Secondary ID [1] 306354 0
Nil known
Universal Trial Number (UTN)
Trial acronym
IMPLEMENT-CD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Crohn's Disease 325156 0
Condition category
Condition code
Oral and Gastrointestinal 322561 322561 0 0
Crohn's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Exclusive Enteral Nutrition (EEN) is a diet-based therapy for Crohn's disease that involves consumption of a specialised formula (polymeric, low-lactose, fibre-free liquid formula) while excluding all foods and fluids from diet with the exception of water. The liquid formula is contained in bottles and depending on estimated individual nutritional requirements, patients will typically consume 4-8 bottles over the course of a day to provide 100% of their required nutrition and caloric intake for the day.

All enrolled patients will have a baseline face-to-face dietetic assessment by a clinical dietitian (Dietitians Australia registered) prior to commencement of therapy. Estimated nutritional requirements and hence the amount of formula for daily consumption to meet these requirements will be calculated by the dietitian. Verbal education and generic written information about EEN (adapted from the patient information sheets by Australasian Society of Parenteral and Enteral Nutrition available online) will be given to patients.
EEN will be supplied for the duration of therapy to the participants at no cost.
Patients will have baseline blood and stool samples collected as well as radiological assessment with gastrointestinal ultrasound (GIUS) performed by a GIUS accredited gastroenterologist.

Patients will be reviewed by a dietitian at week 2, week 4 and week 6 of therapy. Each appointment lasting 20-30 minutes in duration. Visits will be conducted face to face at the hospital dietitian clinic or via telephone. Patients will be assessed for adherence and tolerability to therapy, satiety, clinical response, and nutritional status.

Adherence to therapy will be assessed by the dietitian. This involves direct questioning about self-reported amount of formula used, consumption of other foods or drinks, palatability.

Food and fluid re-introduction will occur over 3-5 days at the end of 6 weeks of therapy. Verbal education and an information sheet on diet post EEN will be given to patients.
Intervention code [1] 322921 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 330547 0
Composite outcome: percentage of patients with:
1. Clinical response as measured by Crohn's disease activity index (CDAI) reduction of greater than 100 points from baseline OR clinical remission as measured by CDAI less than 150 points
AND/OR
2. Objective response OR remission as demonstrated by one of:
a. Gastrointestinal ultrasonographic (GIUS) response as defined as greater than or equal to 25% bowel wall thickness (BWT) reduction from baseline (mm) OR
b. GIUS remission as defined as all of: BWT normalisation, colour Doppler signal less than or equal to 1, normal echo stratification, and absence of inflammatory fat OR
c. Biochemical response as defined as faecal calprotectin (FCP) level reductions of greater than or equal to 50% from baseline OR
d. Biochemical remission defined as FCP levels less than 100 microg/g
Timepoint [1] 330547 0
6 weeks aftering starting treatment
Secondary outcome [1] 406588 0
Clinical remission: perecentage of patients with a Harvey Bradshaw Index as measured by HBI less than 4
Timepoint [1] 406588 0
2 weeks, 6 weeks and 12 weeks after starting treatment
Secondary outcome [2] 406589 0
Patient reported outcomes (PRO): percentage of patients with PRO2 remission as defined as reporting stool frequency less than or equal to 3 and abdominal pain less than or equal to 1 (not worse than baseline) with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit
Timepoint [2] 406589 0
2 weeks, 6 weeks and 12 weeks after starting treatment
Secondary outcome [3] 406591 0
Food-related Quality of Life: Change in patient reported Food-related quality of life as assessed by the Food-related quality of life (FRQoL-29) score compared to baseline score
Timepoint [3] 406591 0
12 weeks after starting treatment
Secondary outcome [4] 406594 0
Quality of Life: Change in patient reported general quality of life as assessed by Short Inflammatory Bowel Disease Questionnaire (SIBDQ) score
Timepoint [4] 406594 0
6 weeks after starting treatment
Secondary outcome [5] 406596 0
Radiological remission: percentage of patients with radiological remission as defined as all of: BWT normalisation, colour Doppler signal less than or equal to 1, normal echo stratification, and absence of inflammatory fat

The most affected bowel segment at BL was used for all GIUS parameters
Timepoint [5] 406596 0
6 weeks after starting treatment
Secondary outcome [6] 406601 0
Biochemical remission: percentage of patients with biochemical remission defined as FCP levels <100 microg/g
Timepoint [6] 406601 0
2 weeks, 6 weeks, 12 weeks after starting treatment
Secondary outcome [7] 406605 0
Safety: safety of the EEN therapy measured by withdrawal from study due to adverse effects and records of any adverse events as assessed by telephone/in-person follow up dietitian review.

Adverse events captured include: increased stool frequency of type 6/7 as per the BSFS, increase in abdominal pain severity (based on 11 point numeric rating scale [NRS] ranging from 0 [No pain] to 10 [Worst imaginable pain]), constipation (as defined as difficulty passing bowel motion or reduced frequency of bowel movements to less than 3/week), nausea and/or vomiting, hunger, or fatigue. Severity will be assessed by Common Terminology Criteria for Adverse Events (CTCAE4).
Timepoint [7] 406605 0
6 weeks after starting treatment
Secondary outcome [8] 406606 0
Therapy Adherence: Percentage of patients able to maintain complete exclusion of non-prescribed dietary intake and consume the minimum prescribed amount of EEN during course of therapy as self-reported by patient during semi-structured one-to-one dietitian review.
Timepoint [8] 406606 0
2 weeks, 4 weeks and 6 weeks after starting treatment
Secondary outcome [9] 406609 0
Protocol feasibility outcome: proportion of patients who completed their prescribed duration of EEN, clinical assessment, radiological assessment by GIUS and biochemical assessment within timeframe as assessed by audit of study records
Timepoint [9] 406609 0
6 weeks after starting treatment
Secondary outcome [10] 406614 0
Health Economics: Exploratory outcome on the cost-effectiveness and resource utilization of EEN as assessed by calculating resource utilisation and cost of therapy from hospital medical records and Medicare Benefits Schedule (MBS) data.
Timepoint [10] 406614 0
30 days, 42 days, 60 days and 90 days after starting treatment

Eligibility
Key inclusion criteria
1. Individuals with a formal diagnosis of Crohn’s Disease which may include histology consistent with CD, clinical diagnosis of active CD or disease visible by endoscopy or radiology or an elevated FC.
2. Active Crohn’s Disease as assessed by the treating clinician as demonstrated by:
A. Clinical evidence with CDAI score > 150 AND/OR
B. Radiological evidence with GIUS or magnetic resonance enterography (MRE) demonstrating active disease AND/OR
C. Biochemical evidence with FCP > 100 microg/g
3. Individuals under the care of an IBD Service and Gastroenterologist across the Central Adelaide Local Health Network (CALHN)
4. Provide informed consent to participate in the study
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Individuals with significant medical or cognitive/psychiatric comorbidities that would impair ability to provide consent, consistently adhere to treatment or complete questionnaires required for study outcome measures
2. Individuals where EEN was prescribed for indications of pre-surgical optimisation or downgrading of disease prior; management of abdominal abscess
3. Individuals whose cause of symptoms is deemed to be infectious, iatrogenic or unrelated to underlying pathology of Crohn’s disease
4. Individuals with severe co-morbidities as judged by the treating clinician

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
Safety/efficacy
Statistical methods / analysis
Power calculations were based on adult EEN therapy studies in literature and local quality improvement projects. The sample size of 50 is required.

The primary analysis will be an intention-to-treat (ITT) analysis with a secondary per protocol analysis. Last recorded values will be carried forward in the ITT analysis where a protocol breach or drop out may occur. The statistical analysis will include linear mixed effects models with adjustment for confounding factors.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/04/2022
Actual
1/04/2022
Date of last participant enrolment
Anticipated
1/09/2023
Actual
Date of last data collection
Anticipated
2/12/2023
Actual
Sample size
Target
50
Accrual to date
31
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 21795 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [2] 21796 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 36853 0
5000 - Adelaide
Recruitment postcode(s) [2] 36852 0
5011 - Woodville

Funding & Sponsors
Funding source category [1] 310710 0
Hospital
Name [1] 310710 0
The Queen Elizabeth Hospital (TQEH) Inflammatory Bowel Disease Service
Country [1] 310710 0
Australia
Primary sponsor type
Government body
Name
Central Adelaide Local Health Network (CALHN)
Address
CALHN Research Services
SA Health
Level 3, Roma Mitchell Building
136 North Terrace, Adelaide, SA 5000
Country
Australia
Secondary sponsor category [1] 311927 0
None
Name [1] 311927 0
Address [1] 311927 0
Country [1] 311927 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310290 0
Central Adelaide Health Network (CALHN) Human Research Ethics Committee (HREC)
Ethics committee address [1] 310290 0
CALHN Research Services
Central Adelaide Local Health Network Inc.
SA Health
Level 3, Roma Mitchell Building
136 North Terrace, Adelaide, SA 5000
Ethics committee country [1] 310290 0
Australia
Date submitted for ethics approval [1] 310290 0
18/02/2022
Approval date [1] 310290 0
07/03/2022
Ethics approval number [1] 310290 0
16053

Summary
Brief summary
Exclusive enteral nutrition (EEN) is a nutrition-based treatment for Crohn’s Disease (CD) with numerous advantages compared to current conventional therapies. While its efficacy has been demonstrated in adult CD patients, EEN remains an underutilised therapy due to a number of factors including uncertainties around the optimal regimen, monitoring and treatment targets. While frameworks have been established to aid decision-making and prescription, evidence to support these recommendations is limited.
This multi-centre single arm pilot clinical study aims to meet this clinical need through prospectively evaluating the efficacy and feasibility of a protocolised approach to delivering exclusive enteral nutrition in adult patients with active Crohn's Disease. Participants who meet inclusion criteria and provide consent will receive a 6 week course of exclusive enteral nutrition under the guidance of an experienced dietitian with regular follow up. This study's primary outcome is the clinical response or remission and/or objective response or remission as demonstrated by normalisation of inflammatory biomarkers or resolution of intestinal inflammation on gastrointestinal ultrasound. Our study will also assess the impact of EEN on disease activity utilising clinical, biochemical, radiological, patient reported outcome measures. Adherence to the therapy and protocol as well as tolerability to EEN will also be assessed. Protocol feasbility and fidelity will be analysed along with health economic data to evaluate the cost-effectiveness of the protocol. Changes in colonic microbial composition, diversity and function post EEN therapy.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 117142 0
Dr Mattthew K.W. Chu
Address 117142 0
Level 4C
TQEH IBD Service
TQEH
28 Woodville Road
Woodville South
SA 5011
Country 117142 0
Australia
Phone 117142 0
+61 8 8222 8984
Fax 117142 0
Email 117142 0
matthew.chu@sa.gov.au
Contact person for public queries
Name 117143 0
A/Prof Robert V. Bryant
Address 117143 0
Level 4C
TQEH IBD Service
TQEH
28 Woodville Road
Woodville South
SA 5011
Country 117143 0
Australia
Phone 117143 0
+61 8 8222 8984
Fax 117143 0
Email 117143 0
robert.bryant@sa.gov.au
Contact person for scientific queries
Name 117144 0
A/Prof Robert V. Bryant
Address 117144 0
Level 4C
TQEH IBD Service
TQEH
28 Woodville Road
Woodville South
SA 5011
Country 117144 0
Australia
Phone 117144 0
+61 8 8222 8984
Fax 117144 0
Email 117144 0
robert.bryant@sa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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.