Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616001149459
Ethics application status
Approved
Date submitted
16/08/2016
Date registered
24/08/2016
Date last updated
10/07/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
The Canadian version of the food for irritable bowel syndrome study
Scientific title
The CanaFIBS study: a randomised control trial comparing two dietary approaches and their effect on clinical and microbiological parameters in adults with Irritable Bowel Syndrome
Secondary ID [1] 289940 0
Nil known
Universal Trial Number (UTN)
U1111-1186-5261
Trial acronym
CanaFIBS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Irritable bowel syndrome 299924 0
Condition category
Condition code
Oral and Gastrointestinal 299820 299820 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants with small intestinal bacterial overgrowth (SIBO) will be randomized to one of two dietary education protocols. Either a low FODMAP (as per the Monash University low FODMAP app) or a low FODMAP, low sugar (<5% of total energy to come from free sugar), reduced fat diet (<25% of total energy) and instructed to avoiding snacking. In both diets participants are to avoid all high FODMAP foods.

There is a one month "run in" period before the participants receive their dietary education where participants will eat their usual diet.. This is to control for the natural variation in the microbiome.

Participants will be seen by a NZ registered dietitian with 10 years experience. All dietary education sessions will be conducted with the dietitian individually. Participants in each group will receive an initial 1 hour session with the dietitian. At this session they will receive a written handout explaining the diet and containing lists of food and a separate recipe book. (The handouts will be different between groups.) They will have an optional second 30 minute education session in the intensive phase (this is when participant's are asked to significantly reduce all FODMAP molecules). After the 2 month data collection they will have a 30 minutes session with the dietitian on rechallenging foods to tolerance. This session will be accompanied by a second handout. They will have the option of another 1 session discussing the process of food rechallenges (four weeks after the initial rechallenge education).The overall duration of the intervention period is 6 months. All patient education will be conducted face to face in a healthcare setting at St Joseph's Hospital, London, Ontario.

Timeline for diets
Baseline to end of "run in" period; follow usual diet
End of "run in" period to 2 month data collection: on the intensive phase of the diet
2 month to 6 month data collection: participants are rechallenging foods and then following the diet that they are able to tolerate.

Adherence to the diet will be measured by 8 telephone diet recalls conducted by two nutrition students. They will be checking for evidence of high FODMAP food intake and reporting on this.
Intervention code [1] 295623 0
Lifestyle
Intervention code [2] 295694 0
Treatment: Other
Comparator / control treatment
The control treatment is a standard low FODMAP diet alone.
Participants will receive the same number of dietary education sessions.
Control group
Active

Outcomes
Primary outcome [1] 299296 0
1. Change in Irritable bowel syndrome symptom severity as measured on the IBS SSS developed by Francis et al (1996)
Timepoint [1] 299296 0
Baseline, after the one month "run in" period, end of two months and end of 6 months.

Baseline and after the one month "run in" are two separate time points.
Primary outcome [2] 299297 0
2. Presence or absence of small intestine bacterial overgrowth on repeat glucose breath test.

This will be measured on the Quintron gas analyser. Participants will have an overnight fast before conducting the test. Breath samples will be analysed at 15 minute intervals for a two hour period.. A positive breath test is defined as an increase in either breath hydrogen or breath methane of >=12ppm from baseline.
Timepoint [2] 299297 0
Baseline and 2 months after beginning the dietary education.

Baseline is one month before the end of the "run in" period. 2 months is 2 months after the beginning of dietary education which begins at the end of the "run in" period.
Secondary outcome [1] 326773 0
1. Change in IBS quality of life questionnaire (Drossmann 1998)
Timepoint [1] 326773 0
To be measured at baseline, 2 months and 6 months.
Secondary outcome [2] 326774 0
Change in microbiome.

DNA will be extracted and sequenced and will be compared using techniques designed for the analysis or compositional data.
Timepoint [2] 326774 0
At baseline, after the "run in" period, at 2 months after dietary education commenced and after 6 months.
Secondary outcome [3] 326824 0
Subscales within the IBS symptom severity scoring system:
-Severity of pain (0-100)
-Frequency of pain (0-10)
Maximum number of bowel motions
Timepoint [3] 326824 0
Baseline, end of "run in" period, end of 2 months, end of 6 months.
Secondary outcome [4] 326825 0
Change in metabolome
LC/MS and GC/MS will be used to detect the small molecu les present. Data will then be analysed using techniquest designed for the analysis of compositional data
Timepoint [4] 326825 0
Baseline, after the "run in period" end of 2 months. end of 6 months.
Secondary outcome [5] 326826 0
Physical activity questionnaire (PAAQ).
This is Canadian specific
Timepoint [5] 326826 0
Baseline, end of 2 months, end of 6 months.
Secondary outcome [6] 326827 0
Blood tests: Hb, serum iron, serum ferritin, transferrin saturation, cholesterol, vitamin D, calcium, vitamin B12
Timepoint [6] 326827 0
Baseline, end of 2 months, end of 6 months
Secondary outcome [7] 326828 0
Change in nutritional intake. This will be measured using the Diet history questionnaire (a North American) food frequency questionnaire.
There are two versions one which measures intake over the last year and the other that measures intake over the last month.
Timepoint [7] 326828 0
At baseline the one year version will be used.

After the "run in" period, after 2 months and after 6 months the one month version will be used.

Eligibility
Key inclusion criteria
IBS (D) or IBS (M) according to Rome III and fluent in English
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Organic gastrointestinal disease (e.g. coeliac, IBD),
Diabetes,
Serious neurological or respiratory conditions
Previous gastrointestinal surgery (except appendectomy),
Pancreatitis,
Previous radiotherapy to the abdominal area or chemotherapy,
Pregnancy and lactation,
Antibiotics or probiotics within the last 6 weeks,

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)
Participant numbers were randomised by someone not directly involved in the study. Prior to the first dietary education the research dietitian and study co-ordinator will be informed of the dietary education
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Used the website https://www.random.org/
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint/s
Statistical methods / analysis
A difference of 100 points on the IBS symptom severity scoring system (IBS SSS) was used as a measure of clinical significance, although a change in as little as 50 points is deemed clinically significant {Francis, 1997}. This was much closer to changing categories of IBS: e.g. from severe to moderate of from moderate to mild. Patient non attendance at dietetic appointments are ~20% in the candidate’s experience and this was used a proxy for likely drop outs. An alpha of 0.05 was selected with 80% power. Therefore 33 participants were needed in each group for a total of 66 participants. It was expected that up to 300 participants with IBS (D) would be needed to find 66 SIBO positive patients as about 25% of IBS(D) patients have SIBO when glucose is used as the substrate.

Statistical analysis will be performed using Stata (Version 13.1 CITY, TX, USA) and R for the microbiome analysis. Data will be presented as mean and standard deviation unless otherwise stated. Students’ t tests will be used to compare baseline continuous data and Fisher’s exact test for categorical data. Paired students’ t test will be used to compare differences in continuous variables between baseline, 2 months and 6 months. ANCOVA will be used to test whether there is an intergroup difference between baseline, two months and six months. A p value of =0.05 will be deemed statistically significant. See section 2.4 on CoDa analysis on the microbiome. Microbiome and metabolomics analysis will be presented in PCA and heatmaps as appropriate.

Recruitment
Recruitment status
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
Actual
19/04/2016
Date of last participant enrolment
Anticipated
9/01/2017
Actual
1/06/2017
Date of last data collection
Anticipated
30/08/2017
Actual
30/08/2017
Sample size
Target
66
Accrual to date
Final
13
Recruitment outside Australia
Country [1] 8100 0
Canada
State/province [1] 8100 0
Ontario

Funding & Sponsors
Funding source category [1] 294312 0
University
Name [1] 294312 0
University of Otago
Country [1] 294312 0
New Zealand
Funding source category [2] 294313 0
University
Name [2] 294313 0
GutHealthNetwork, University of Otago
Country [2] 294313 0
New Zealand
Funding source category [3] 294314 0
Charities/Societies/Foundations
Name [3] 294314 0
NZ Society of Gastroenterology
Country [3] 294314 0
New Zealand
Primary sponsor type
Individual
Name
Michael Schultz
Address
Department of Medicine
9th Floor, Dunedin Hospital
Great King Street
Dunedin Central
Dunedin 9016
New Zealand
Country
New Zealand
Secondary sponsor category [1] 293153 0
None
Name [1] 293153 0
Not applicable
Address [1] 293153 0
Not applicable
Country [1] 293153 0
Other collaborator category [1] 279161 0
Individual
Name [1] 279161 0
Adam Rahman
Address [1] 279161 0
St Joseph's Health Care London
268 Grosvenor St
London
Ontario
N6A 4V2
Country [1] 279161 0
Canada

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295739 0
Western University Health Science Research Ethics Board
Ethics committee address [1] 295739 0
Western University
Research Support Services Building Rm 5150
London
Ontario
N6G 1G9
Ethics committee country [1] 295739 0
Canada
Date submitted for ethics approval [1] 295739 0
11/11/2015
Approval date [1] 295739 0
27/11/2015
Ethics approval number [1] 295739 0

Summary
Brief summary
There are two parts to this protocol. 1. An observational study comparing characteristics of participants who had IBS with diarrhea or IBS (M) with and without SIBO. 2. A randomised dietary education trial where participants with SIBO receive education on either a low FODMAP diet or a diet low in FODMAP, fat, sugar and avoiding snacking. This registration is for the RCT only. We will be registering the observational study separately.

Potential participants with IBS will be invited to participate. After signing a consent form participants will complete an IBS symptom severity scoring system (1), an IBS quality of life questionnaire (2), the hospital anxiety and depression index (3), a visual analogue scale for flatulence (0-100), a general health questionnaire, a physical activity questionnaire and “trigger” foods questionnaire online via REDCAP (Research electronic data capture), They will complete a separate food frequency questionnaires (FFQ) online (the DHQ measuring intake over the last year). Participants will complete anthropometric measures, and give urine, blood and fecal samples. They will be screened for SIBO using breath tests with 75g glucose in 200ml water as the substrate. A positive breath test is defined as an increase of =>12ppm hydrogen and methane from baseline. Blood samples will be analysed for serum B12, serum vitamin A, cholesterol, iron studies, and haemoglobin.

For participants without SIBO this currently is the end of the study. We will be including their data within publications that may be produced as a part of the overall study. Should we recruit a sufficient sample this will be a large IBS population for which we will analyse the microbiome and metabolome using next generation sequencing techniques.

Those with SIBO will have a one month “run in” period before being provided with the dietary education. Participants will be randomised to either a low FODMAP diet education or a low FODMAP plus low sugar, reduced fat and avoiding of snacking. Data will be recollected at 2 months after which time the participants will begin the food rechallenges. The final data collection point will be a six months after the commencement of dietary education when participants should have liberalised their diet according to their individual tolerances.

Faecal samples and urine samples will be stored at -80C until processed and analysed. DNA will be extracted and sequenced using next generation sequencing techniques. Urine samples will be analysed for metabolites using liquid chromatography (LC/MS) and gas chromatography (GC/MS). Data generated from the microbiome and metabolome analysis will be analysed using a compositional data analysis techniques.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 68282 0
A/Prof Michael Schultz
Address 68282 0
Department of Medicine
9th Floor, Dunedin Hospital
Great King Street
Dunedin Central
Dunedin 9016
New Zealand
Country 68282 0
New Zealand
Phone 68282 0
+64 3 474 0999
Fax 68282 0
Email 68282 0
[email protected]
Contact person for public queries
Name 68283 0
Ms Ruth Harvie
Address 68283 0
c/- the Canadian centre for the human microbiome and probiotics
Lawson Research Institute
268 Grosvenor St
London
Ontario
N6A 4V2
Country 68283 0
Canada
Phone 68283 0
+1 519 317 2384
Fax 68283 0
Email 68283 0
[email protected]
Contact person for scientific queries
Name 68284 0
A/Prof Michael Schultz
Address 68284 0
Department of Medicine
9th Floor, Dunedin Hospital
Great King Street
Dunedin Central
Dunedin 9016
Country 68284 0
New Zealand
Phone 68284 0
+64 3 474 0999
Fax 68284 0
Email 68284 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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