Please be advised that due to the high volume of submissions, the ANZCTR is currently experiencing delays in processing submissions from those outside of Australia and New Zealand. As the ANZCTR is funded by Australia and New Zealand, we must prioritise submissions from these countries first. International submissions should allow additional time for registration. Apologies for any inconvenience caused.

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Trial registered on ANZCTR


Registration number
ACTRN12619000911190
Ethics application status
Approved
Date submitted
6/06/2019
Date registered
28/06/2019
Date last updated
28/06/2019
Date data sharing statement initially provided
28/06/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
The Australian Inflammatory Bowel Disease Microbiome Study - The AIM Study
Scientific title
Defining the Australian Inflammatory Bowel Disease Microbiome Study - The AIM Study
Secondary ID [1] 298419 0
Nil known
Universal Trial Number (UTN)
U1111-1234-7516
Trial acronym
AIM
Linked study record
None

Health condition
Health condition(s) or problem(s) studied:
Inflammatory Bowel Disease 313139 0
ulcerative colitis 313291 0
colitis 313292 0
Crohn's disease 313293 0
Condition category
Condition code
Oral and Gastrointestinal 311612 311612 0 0
Inflammatory bowel disease
Oral and Gastrointestinal 311737 311737 0 0
Crohn's disease
Inflammatory and Immune System 311738 311738 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Patients with Inflammatory Bowel Disease

Male and female (nonpregnant) patients with either ulcerative colitis or Crohn's disease undergoing follow-up colonoscopy for disease activity assessment will have samples of large bowel mucosa, peripheral blood, urine and stool collected at colonoscopy (stool and urine collection tubes/instructions will be provided in advance, so patients can bring samples to their colonoscopy appointment).

IBD patients who are eligible for the study but are not requiring colonoscopy, will be invited to participate in the study by local research teams either at the current clinic visit, a future scheduled clinic visit or a separate visit to the local clinical research facility. At this appointment, peripheral blood, urine oral swab and stool will be collected (stool and urine collection tubes/instructions will be provided in advance, so patients can bring samples to their appointment).

All IBD patients will be asked to complete a series of validated questionnaires detailing patient reported outcomes/environmental exposures as well as dietary habits. Completion of the questionnaires will be requested at study entry and at the end of 12 and 24 months. A limited patient reported measure of disease activity will also be requested alongside 3 monthly stool sampling.

To allow further detailed analyses of the gut microbiota, patients will be asked to provide oral swab and stool samples, for microbiota analysis and measurement of host protein levels including faecal calprotectin, every 3 months for 24 months.

In the event that patients experience an increase in symptoms, they will be advised to contact their IBD clinical team as per usual clinical management, but they will be requested to provide additional oral swab and stool samples during the episode of flare (defined by a standardised clinical definition), in addition to the 3-monthly regular request.

Sample and Data Collection

For participants undergoing colonoscopies, up to six additional intestinal tissue samples will be collected along with the biopsy samples that are routinely taken during this procedure for clinical management. Approximately 20ml of blood (4 teaspoons) will also be collected along with the blood tests that are routinely taken at this time. In addition, patients will be asked to provide a urine sample (50 ml) in individual sterile collection tubes, an oral swab, and a stool sample will be collected by the participant before commencing bowel preparation the previous night (collection kit/instructions provided in advance).

For participants attending IBD outpatient clinics or participants attending a clinical research facility, 30ml of blood (6 teaspoons), 50 mL of urine, oral swab, and a stool sample will be collected when they initially enter the study. At subsequent appointments if participants are having blood collected as part of routine clinical management, we will collect an additional sample.

Questionnaires
Participants will be asked to fill in a Food Frequency Questionnaire and a food avoidance questionnaire online in one of their visits to the clinic (or they can be given a user login and password to fill in the questionnaire at home). These questionnaires are aiming to evaluate the participants’ usual eating and drinking habits over the last 12 months (e.g. What type of spread or oil did you usually put on your bread? with the following answers to select from: none, butter, butter-margarine blends [e.g. Devondale Extra Soft or Dairy Soft, Western Star spreadable varieties], margarine, olive oil).

Participants will be asked to record every food item they eat in a specialised smartphone application for 5 days (4-week days and 1 weekend day, not necessarily consecutive). If they are not smartphone users, they will be provided with a 5-day diet diary which they will be asked to fill in and return in their next visit to the clinic. Participants will complete this at study entry, at 12 and 24 months.

All participants will also complete a limited participant reported outcomes measures score which will be returned with their 3 monthly stool and oral samples.

Participants will also be asked to complete a lifestyle factor questionnaire during their visits to the clinic (or they can be given a user login and password to fill in the questionnaire at home). This lifestyle questionnaire is aiming to evaluate the participants’ usual lifestyle habits over the last 12 months (e.g. level of exercise, sleep habits, travel habits, use of health supplements and complementary medicines. A paper-based format will be available for participants who cannot complete it online. Participants will complete this at study entry, at 12 and 24 months.

For all participants in this study, the researchers may access their hospital records for demographic and/or clinical information solely for the purposes of this study.

Intervention code [1] 314670 0
Not applicable
Comparator / control treatment
Population controls
(Nonpregnant) partner/spouse and family members of case participants will be invited to participate in the study as controls by local research teams when they accompany their IBD affected family member to clinic appointments. Population controls will be recruited through publicity and word of mouth and recruited at clinical research facilities in specific AIM study clinics. Upon consent, peripheral blood, urine, oral swab and stool will be collected in the same manner as IBD patients, (stool and urine collection tubes/instructions will be provided in advance, so participants can bring samples to their next follow-up appointment).

All healthy controls will be asked to complete a series of validated questionnaires detailing participant reported outcomes/environmental exposures and dietary habits. Completion of the questionnaire will be requested at study entry and at the end of 12 and 24 months.

To allow further detailed analyses of the gut microbiota, participants will be asked to provide oral swab and stool samples, for microbiota analysis and measurement of host protein levels including faecal calprotectin, every 3 months for 24 months. Participants will be asked to self-collect samples at home (following previously provided instructions) and return to the central processing lab (MRC at St George Hospital) in postage paid envelopes. A limited participant reported measure of wellness will also be requested alongside 3 monthly stool sampling.

Sample and Data Collection

For participants undergoing any incidental colonoscopy procedures, up to six additional intestinal tissue samples will be collected along with the biopsy samples that are routinely taken during this procedure for clinical management. Participants do not require colonoscopy as part of the AIM study.
Approximately 20ml of blood (4 teaspoons) will also be collected along with the blood tests that are routinely taken at this time. In addition, patients will be asked to provide a urine sample (50 ml) in individual sterile collection tubes, an oral swab, and a stool sample will be collected by the participant before commencing bowel preparation the previous night (collection kit/instructions provided in advance).

When attending the clinical research facility, 30ml of blood (6 teaspoons), 50 mL of urine, oral swab, and a stool sample will be collected when they initially enter the study. At subsequent appointments if participants are having blood collected as part of routine clinical management, we will collect an additional sample.

Questionnaires
Participants will be asked to fill in a Food Frequency Questionnaire and a food avoidance questionnaire online in one of their visits to the clinic (or they can be given a user login and password to fill in the questionnaire at home). These questionnaires are aiming to evaluate the participants’ usual eating and drinking habits over the last 12 months (e.g. What type of spread or oil did you usually put on your bread? with the following answers to select from: none, butter, butter-margarine blends [e.g. Devondale Extra Soft or Dairy Soft, Western Star spreadable varieties], margarine, olive oil).

Participants will be asked to record every food item they eat in a specialised smartphone application for 5 days (4-week days and 1 weekend day, not necessarily consecutive). If they are not smartphone users, they will be provided with a 5-day diet diary which they will be asked to fill in and return in their next visit to the clinic. Participants will complete this at study entry, at 12 and 24 months.

All participants will also complete a limited participant reported outcomes measures score which will be returned with their 3 monthly stool and oral samples.

Participants will also be asked to complete a lifestyle factor questionnaire during their visits to the clinic (or they can be given a user login and password to fill in the questionnaire at home). This lifestyle questionnaire is aiming to evaluate the participants’ usual lifestyle habits over the last 12 months (e.g. level of exercise, sleep habits, travel habits, use of health supplements and complementary medicines. A paper-based format will be available for participants who cannot complete it online. Participants will complete this at study entry, at 12 and 24 months.

For all participants in this study, the researchers may access their hospital records for demographic and/or clinical information solely for the purposes of this study.

Control group
Active

Outcomes
Primary outcome [1] 320311 0
• To define the difference in alpha-diversity measurements in gut microbiota composition between IBD and control participant stool samples
Timepoint [1] 320311 0
0, 3, 6, 9, 12, 15, 18, 21 and 24 months
Primary outcome [2] 320312 0
To determine whether a reduction in Faecalibacterium prausnitzii in stool samples is associated with onset of IBD symptoms
Timepoint [2] 320312 0
0, 3, 6, 9, 12, 15, 18, 21 and 24 months
Primary outcome [3] 320313 0

• To determine whether IBD relapse can be determined by tracking longitudinally collected microbiota with linkage to medical records
Timepoint [3] 320313 0
0, 3, 6, 9, 12, 15, 18, 21 and 24 months
Secondary outcome [1] 371214 0
•To define the difference in alpha-diversity measurements in gut microbiota composition of stool samples between Australian and other geographic area IBD populations
Timepoint [1] 371214 0
0, 3, 6, 9, 12, 15, 18, 21 and 24 months
Secondary outcome [2] 372009 0
To assess whether IBD patient dietary habits reflect health status (Food avoidance questionaire, dietary analysis from food diary and food frequency questionaires)

Food diary (Easy diet diary by Xyris), Food avoidance questionaire and Dietary Questionaire (food frequency questionaire from Cancer Council Victoria) are validated dietary analysis tools. The composite data will be analysed to address this secondary outcome.
Timepoint [2] 372009 0
0, 3, 6, 9, 12, 15, 18, 21 and 24 months
Secondary outcome [3] 372010 0
To assess whether IBD patient lifestyle factors reflect health status (SF-36, IBDQ)

SF-36 and IBDQ are validated tools and the composite data will be analysed to address this secondary outcome.
Timepoint [3] 372010 0
0, 3, 6, 9, 12, 15, 18, 21 and 24 months

Eligibility
Key inclusion criteria
Participants must be:
1. Aged between 6 to 80 years old at study entry
2. Able to give informed consent/assent
3. Confirmed CD or UC (Copenhagen criteria (adults) and Paediatric Crohn's disease Activity Index (PCDAI) and Paediatric Ulcerative colitis Activity Index (PUCAI) (physician global assessment) or newly-diagnosed
4. For control groups, no history of gastrointestinal inflammation or IBD
Minimum age
6 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Female participants must not be pregnant or breast-feeding at time of recruitment into study
2. Unable to provide informed consent (patient or parent/carer) or comply with follow-up

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
We will initially produce descriptive analyses of the distribution of measured parameters in the study cohort. These will be presented as mean/sd for normally distributed variables, and median/interquartile range for those not normally distributed. We will present similar statistics for the subjects in whom flares did and did not occur and will assess the differences between these populations using a t-test for normally distributed or Mann–Whitney–Wilcoxon test for non-normally distributed parameters. We will then examine the flare rates of the groups firstly in univariable analyses (assessing the difference in proportions of the groups experiencing flare), and then in multivariable Cox models in which we will consider as potential confounders baseline variables including disease type, location, behaviour, smoking status, therapy, CRP and faecal calprotectin.

We will test for associations between measured parameters and microbiome measures, listing all phyla, genera, species or pathway that correlate significantly (Benjamini-Hochberg FDR < 0.05) with measured parameters under a Kruskal-Wallis test.
We will generate two plots, each showing all samples on the first two principal coordinates of clades (species) and pathways (KO terms), coloured by measured parameters. Principal coordinates will be calculated using the Bray–Curtis distance.

Longitudinal analysis approach. All samples will be stored for a similar length of time, prior to extraction, to reduce potential bias introduced through storage. In patients who flare, gut microbiota comparisons will be made between samples collected before, during and after flare and compared with baseline.


Recruitment
Recruitment status
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)
ACT,NSW
Recruitment hospital [1] 13913 0
St George Hospital - Kogarah
Recruitment hospital [2] 13914 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [3] 13915 0
Concord Repatriation Hospital - Concord
Recruitment hospital [4] 13916 0
Liverpool Hospital - Liverpool
Recruitment hospital [5] 13917 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [6] 13918 0
Blacktown Hospital - Blacktown
Recruitment hospital [7] 13919 0
Sydney Children's Hospital - Randwick
Recruitment hospital [8] 13920 0
The Canberra Hospital - Garran
Recruitment hospital [9] 13921 0
Wollongong Hospital - Wollongong
Recruitment hospital [10] 13922 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [11] 13923 0
Prince of Wales Hospital - Randwick
Recruitment hospital [12] 13924 0
The Children's Hospital at Westmead - Westmead
Recruitment postcode(s) [1] 26684 0
2217 - Kogarah
Recruitment postcode(s) [2] 26685 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 26686 0
2139 - Concord
Recruitment postcode(s) [4] 26687 0
2170 - Liverpool
Recruitment postcode(s) [5] 26688 0
2050 - Camperdown
Recruitment postcode(s) [6] 26689 0
2148 - Blacktown
Recruitment postcode(s) [7] 26690 0
2031 - Randwick
Recruitment postcode(s) [8] 26691 0
2605 - Garran
Recruitment postcode(s) [9] 26692 0
2500 - Wollongong
Recruitment postcode(s) [10] 26693 0
2065 - St Leonards
Recruitment postcode(s) [11] 26694 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 302967 0
Charities/Societies/Foundations
Name [1] 302967 0
Gastroenterological Society of Australia
Address [1] 302967 0
101/517 Flinders Ln, Melbourne VIC 3000
Country [1] 302967 0
Australia
Funding source category [2] 302969 0
Hospital
Name [2] 302969 0
Sydney Childrens Hospital Research Grants
Address [2] 302969 0
High St, Randwick NSW 2031
Country [2] 302969 0
Australia
Funding source category [3] 302970 0
Charities/Societies/Foundations
Name [3] 302970 0
Crohn's Colitis Australia
Address [3] 302970 0
4/363 Camberwell Rd, Camberwell VIC 3124
Country [3] 302970 0
Australia
Primary sponsor type
University
Name
University of New South Wales
Address
High St, Kensington, NSW 2052
Country
Australia
Secondary sponsor category [1] 302924 0
None
Name [1] 302924 0
Address [1] 302924 0
Country [1] 302924 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303521 0
South Eastern Sydney Local Health District HREC
Ethics committee address [1] 303521 0
Prince of Wales Hospital
G71 East Wing , Edmund Blacket Building
320-346 Barker St, Randwick NSW 2031
Ethics committee country [1] 303521 0
Australia
Date submitted for ethics approval [1] 303521 0
04/07/2018
Approval date [1] 303521 0
06/03/2019
Ethics approval number [1] 303521 0
18/173 (HREC/18/POWH/357)
Ethics committee name [2] 303523 0
University of New South Wales HREC
Ethics committee address [2] 303523 0
High St, Kensington, NSW 2052
Ethics committee country [2] 303523 0
Australia
Date submitted for ethics approval [2] 303523 0
21/05/2019
Approval date [2] 303523 0
Ethics approval number [2] 303523 0
To be given

Summary
Brief summary
IBD is a global disease challenge and common cause of chronic ill-health among young people in Australia, for which there is currently no cure. It affects approximately 1 in 250 Australians aged 5 – 40 years, with almost 75,000 Australians having CD or UC, with this number projected to rise to 100,000 within the next 5 years. Being able to identify people at risk of disease onset, prior to symptomatology, or by preventing symptom progression would yield significant global social impact and economic benefit and plays to the heart of IBD healthcare, namely to improve patient health.

Two recently published studies have highlighted the strengths of utilising longitudinal assessment of the IBD gut microbiome. There is an existing knowledge gap in terms of defining microbiota changes in IBD in Australia. Different populations have differing genetic risk loci and disease prevalence rates in terms of IBD, they also harbour different gut microbes, in part due to varying environmental exposures and dietary habits.

We believe it is timely to initiate such a study to contribute information on the natural history of gut microbiota changes in IBD in Australia. We will adopt state-of-the-art clinical data and sample collection in a large case-controlled cohort to elucidate microbial changes associated with onset of IBD symptomatology, the identification of an ‘at risk’ microbial signature to allow targeted intervention and the generation of novel predictive models of direct translational utility.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 93954 0
Prof Georgina Hold
Address 93954 0
Microbiome Research Centre
St George and Sutherland Clinical School, UNSW Sydney
Level 2, Clinical Sciences Building (WR Pitney), Short Street, St George Hospital, KOGARAH NSW 2217
UNSW SYDNEY NSW 2052 AUSTRALIA
Country 93954 0
Australia
Phone 93954 0
+61 2 9113 1855
Fax 93954 0
Email 93954 0
georgina.hold@unsw.edu.au
Contact person for public queries
Name 93955 0
Prof Georgina Hold
Address 93955 0
Microbiome Research Centre
St George and Sutherland Clinical School, UNSW Sydney
Level 2, Clinical Sciences Building (WR Pitney), Short Street, St George Hospital, KOGARAH NSW 2217
UNSW SYDNEY NSW 2052 AUSTRALIA
Country 93955 0
Australia
Phone 93955 0
+61 2 9113 1855
Fax 93955 0
Email 93955 0
georgina.hold@unsw.edu.au
Contact person for scientific queries
Name 93956 0
Prof Georgina Hold
Address 93956 0
Microbiome Research Centre
St George and Sutherland Clinical School, UNSW Sydney
Level 2, Clinical Sciences Building (WR Pitney), Short Street, St George Hospital, KOGARAH NSW 2217
UNSW SYDNEY NSW 2052 AUSTRALIA
Country 93956 0
Australia
Phone 93956 0
+61 2 9113 1855
Fax 93956 0
Email 93956 0
georgina.hold@unsw.edu.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?
Study protocol
Statistical analysis plan
Informed consent form
Ethical approval
How or where can supporting documents be obtained?
Type [1] 2278 0
Study protocol
Citation [1] 2278 0
Link [1] 2278 0
Email [1] 2278 0
Other [1] 2278 0
Type [2] 2279 0
Ethical approval
Citation [2] 2279 0
Link [2] 2279 0
Email [2] 2279 0
Other [2] 2279 0
Type [3] 2280 0
Informed consent form
Citation [3] 2280 0
Link [3] 2280 0
Email [3] 2280 0
Other [3] 2280 0
Adult control participant
Type [4] 2281 0
Informed consent form
Citation [4] 2281 0
Link [4] 2281 0
Email [4] 2281 0
Other [4] 2281 0
Adult IBD participant
Type [5] 2282 0
Informed consent form
Citation [5] 2282 0
Link [5] 2282 0
Email [5] 2282 0
Other [5] 2282 0
Child/Adolescent Control Participant
Type [6] 2283 0
Informed consent form
Citation [6] 2283 0
Link [6] 2283 0
Email [6] 2283 0
Other [6] 2283 0
Child/Adolescent IBD Participant
Type [7] 2284 0
Informed consent form
Citation [7] 2284 0
Link [7] 2284 0
Email [7] 2284 0
Other [7] 2284 0
Parent/Guardian Control participant
Type [8] 2285 0
Informed consent form
Citation [8] 2285 0
Link [8] 2285 0
Email [8] 2285 0
Other [8] 2285 0
Parent/Guardian IBD participant
Type [9] 2286 0
Informed consent form
Citation [9] 2286 0
Link [9] 2286 0
Email [9] 2286 0
Other [9] 2286 0
Young child control
Type [10] 2287 0
Informed consent form
Citation [10] 2287 0
Link [10] 2287 0
Email [10] 2287 0
Other [10] 2287 0
Young child IBD
Type [11] 2288 0
Statistical analysis plan
Citation [11] 2288 0
Link [11] 2288 0
Email [11] 2288 0
Other [11] 2288 0
Statistical analysis plan is included within the protocol
Attachment [11] 2288 0
Summary results
No Results