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Trial registered on ANZCTR


Registration number
ACTRN12620000032954
Ethics application status
Approved
Date submitted
6/12/2019
Date registered
20/01/2020
Date last updated
20/01/2020
Date data sharing statement initially provided
20/01/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomized controlled study of gut health and Fibre-fix in people with IBS who are on a low FODMAP diet
Scientific title
Does Fibre-fix provided to people with Irritable Bowel Syndrome who are consuming a low FODMAP diet improve their gut health, gut microbiome, sleep and mental health?
Secondary ID [1] 299623 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Irritable Bowel Syndrom 314931 0
Gut Health 314932 0
Gut Microbiome 314933 0
Sleep Health 314934 0
Mental Health 314935 0
Dietary Fibre 314936 0
low FODMAP diet 314937 0
Sleep
315148 0
Condition category
Condition code
Oral and Gastrointestinal 313284 313284 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Mental Health 313285 313285 0 0
Depression
Diet and Nutrition 313286 313286 0 0
Other diet and nutrition disorders
Public Health 313287 313287 0 0
Health promotion/education

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Fibre-fix (TM) will be provided to participants who have been clinically diagnosed as IBS patients following a low FODMAP diet. Participants will be randomly allocated to intervention or control group, with both researchers and participants blinded to allocation. Participants in either group will take the Fibre-fix or Control supplement (provided in sachets) for 3 weeks. The first four days will be 1 sachet per day, half in the morning and evening, respectively. The remaining 17 days will be 2 sachets per day, one sachet in the morning and evening, respectively. One package of 38 sachets in total will be provided to each participant at Edith Cowan University Joondalup campus by the researcher of the study.

Participants will be advised on the best procedure for consuming the supplement, and a booklet of education for consumption and the study journey, which is designed specifically for this study, will be provided along with the package of sachets. Related recipes and instruction of taking the supplement have been outlined in the education booklet. The dietary fibre supplement (Fibre-fix) or control supplement can be consumed by mixing with 250-350ml of water and drinking immediately or sprinkling over regular meals as a part of a daily diet.

Sachets were prepared in a food-grade laboratory at Edith Cowan University.

For monitoring adherence to the intervention, participants will be received weekly text message reminders and will be required to return the unused sachets which will also allow calculation of the compliance rate. Consumption of greater than 80% of the sachets (30 sachets) over the three-week period will be considered compliant with the study protocols. Additionally, participants will be asked to complete a daily bowel symptoms checklist that has a column for participants to fill out the time and amount of supplement consumed as an additional way of monitoring compliance.

Common dietary fibre is low in resistant starch whereas Fibre-fix contains a high content of resistant starch from high amylose maize starch.
Intervention code [1] 315880 0
Lifestyle
Intervention code [2] 315881 0
Treatment: Other
Comparator / control treatment
Control treatment is the placebo - common dietary fibre or corn starch. The usage, duration, dose and mode of delivery of the active control are the same as those of the intervention of this study.
Control group
Active

Outcomes
Primary outcome [1] 321772 0
Fecal levels of Short-Chain Fatty Acid, including butyrate, assessed by stool samples provided by participants, using gas-liquid chromatography at Edith Cowan University.
Timepoint [1] 321772 0
Baseline and after the 3-week intervention
Primary outcome [2] 322244 0
Faecal pH value assessed by stool samples provided by participants, using a pH probe.
Timepoint [2] 322244 0
Baseline and after the 3-week intervention
Primary outcome [3] 322245 0
The diversity and abundance of the gut microbiota. This microbial analyses will be performed at the WA Human Microbiome Collaboration Centre, Bentley WA and microbiome signatures will be generated using the Illumina MiSeq platform using uniquely barcoded 16S rRNA gene primers (515-806(V4)) for bacterial and ITS2 primers for fungal profiling (pending on funding), following PCR inhibition assessment of each DNA extract.
Timepoint [3] 322245 0
Baseline and after the 3-week intervention
Secondary outcome [1] 376166 0
Sleep duration, sleep latency, sleep efficiency, total time in bed, and wake after sleep onset. These related sleep quality assessments are generated by the Readiband, a wrist-based wearable sleep monitor. This is a composite secondary outcome.
Timepoint [1] 376166 0
Throughout the whole study, including 1 week of baseline assessment and the 3-week intervention assessment.
Secondary outcome [2] 376267 0
Gut symptoms which will be recorded in a daily bowel symptoms checklist. The checklist is study-specific and modified based on the International Foundation for Functional Gastrointestinal Disorders, Inc. (IFFGD) Symptom diary.
The daily bowel checklist functions as a safety record displaying if the supplement exacerbates participants, and as a compliance record where participants will record the daily consumption time .
Timepoint [2] 376267 0
Baseline (1 week) and during the 3-week intervention
Secondary outcome [3] 377855 0
Depression and anxiety assessed using Depression Anxiety Stress Scale (DASS-21),
Timepoint [3] 377855 0
Baseline and after the 3-week intervention
Secondary outcome [4] 377856 0
Anxiety assessed using the Visceral Sensitivity Index,
Timepoint [4] 377856 0
Baseline and after the 3-week intervention
Secondary outcome [5] 377857 0
Life quality assessed using IBS Quality of Life
Timepoint [5] 377857 0
Baseline and after the 3-week intervention
Secondary outcome [6] 377858 0
Quality of life assessed using WHO (Five) Well-Being Index
Timepoint [6] 377858 0
Baseline and after the 3-week intervention
Secondary outcome [7] 377859 0
Body fat ratio (body composition) obtained using the BOD POD® (Cosmed, Rome, Italy), an Air Displacement Plethysmograph using whole body densitometry to determine body composition (fat vs. lean)
Timepoint [7] 377859 0
Baseline and after the 3-week intervention
Secondary outcome [8] 377860 0
Circumferences of waist and hips - waist/hip ratio, The circumferences will be measured to the nearest 0.1 cm by a Lufkin steel tape in accordance with the international operating procedure for anthropometric assessment.
Timepoint [8] 377860 0
Baseline and after the 3-week intervention
Secondary outcome [9] 377891 0
Dietary intake assessed using a three-day weighed food record completed on a free downloaded smart-phone application - Research Food Diary (Xyris).
Timepoint [9] 377891 0
Baseline and at the end of the 3-week intervention.
Secondary outcome [10] 377900 0
Subjective sleep quality assessed using a questionnaire-the Pittsburgh Sleep Quality Index
Timepoint [10] 377900 0
Baseline and at the end of the 3-week intervention
Secondary outcome [11] 377901 0
Daytime sleepiness assessed using the Epworth Sleepiness Scale questionnaire
Timepoint [11] 377901 0
Baseline and at the end of the 3-week intervention
Secondary outcome [12] 377902 0
Insomnia situation assessed using the Insomnia Severity Index questionnaire
Timepoint [12] 377902 0
Baseline and at the end of the 3-week intervention
Secondary outcome [13] 377903 0
Individual behaviour in sleep hygiene assessed using the Sleep Hygiene Index questionnaire
Timepoint [13] 377903 0
Baseline and at the end of the 3-week intervention
Secondary outcome [14] 377904 0
Restorative quality of sleep assessed using the Restorative Sleep Questionnaire weekly version.
Timepoint [14] 377904 0
Baseline and at the end of the 3-week intervention
Secondary outcome [15] 377915 0
Individuals’ FODMAP intake qualified by an online Food Frequency Questionnaire - the Monash University Comprehensive Nutrition Assessment Questionnaire (CNAQ),
Timepoint [15] 377915 0
Baseline and at the end of the 3-week intervention.
Secondary outcome [16] 378587 0
Boby Mass Index(BMI)

BMI will be calculated through height and bodyweight.
standing height and weight will be measured by a SECA 763 digital column scale (SECA Ltd, USA) with stadiometer to the nearest 0.1cm and 0.1kg, respectively.
Timepoint [16] 378587 0
Baseline and at the end of the 3-week intervention.

Eligibility
Key inclusion criteria
Participants will be between 18 - 65 years old and have been clinically diagnosed with IBS, meeting the Rome IV edition diagnostic criteria by a gastroenterologist, other medical professional or dietitian.
Participants will be on a Low FODMAP Diet for one month prior to the intervention or prepared to restart a Low FODMAP Diet for the duration of the study.
Participants will need to be available to attend the local clinic visits and the ECU Joondalup campus, and be willing to consume the intervention starch sachets as per the requirement.
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Smoking,
• Pregnancy or planning to become pregnant,
• Having a known diagnosis of other gastrointestinal illness (e.g. Inflammatory Bowel Disease, malabsorption of any macronutrients, bowel resection, coeliac disease),
• Previous abdominal or gastrointestinal surgeries, severe mental health and sleep-related conditions (e.g. insomnia), renal or hepatic diseases, and major medical illness,
• Current use of pharmaceutical agents that could modify or treat IBS (e.g. probiotics, antibiotics, eluxadoline, lubiprostone and linaclotide) or sleep conditions,
• Other restrictive dietary patterns or therapies (e.g. gluten-free, low-carbohydrate, or high-protein diets, keto/Paleo-diet),
• Take any prebiotics,
• Any other disease, condition or habit that may interfere with completion of study.

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)
There will be one independent, non study person who will assign A and B to either the intervention or control group. The researcher will not be aware of this allocation until all study data is collected and analysed. The researcher who will collect participant information will be blinded to the group allocation, and provided with the randomisation code A or B in sealed opaque envelopes for each participant through random allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software - computerised sequence generation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Sample size:
The a priori sample size for the proposed study was determined based on the same parameters outlined by McOrist et al., (2011), where a sample size of 50 participants (25 per group) is required to detect a change in log SCFA concentration 0.4 at 80% power and 5% level of significance. Allowing for a 15% drop-out rate, the total sample size will increase to 58 subjects, 29 per group. This sample size is sufficient to detect at least a medium between-within group interaction effect (Cohen’s f = 0.25) in sleep improvement at 80% power and 5% significance level, whereby the corresponding sample size requirement is 34.

Statistical methods:
The demographics information of participants in both groups will be described and compared initially. Descriptive statistics in the form of mean ± standard deviation (SD) will be used to describe numerical variables, and frequencies and proportions for nominal variables. All continuous outcome variables will be examined normality using the Shapiro-Wilk test.

Mixed-model ANOVA will be utilised to assess changes in levels of SCFA, butyrate and faecal pH between- and within-groups. Covariates, including gender and age, will be adjusted in the model. To analyse the gut microbiota, multivariate analysis, a combination of R and Primer7 and Permavona+ (PRIMER-E, Plymouth), will be used. Principal Coordinates Analysis (PCoA) will be deployed to visualise findings. Distance-based linear models (DISTLM) and distance-based redundancy analysis (dbRDA) will be used to integrate microbiome findings with clinical, immune function data and other relevant data that might help explain the relationship between the microbiome findings and other outcomes. If a significant relationship or difference is established at the multivariate level, multiple linear regression (MLR) will be conducted at the univariate level to determine the association between the gut microbiota composition and SCFA level, butyrate levels, faecal pH, diet intake, sleep, mental health. The covariates including gender, age, intervention compliance and IBS subtype will be considered as confounding variables and are adjusted in the MLR modelling.

The dependent variables (DVs) from the questionnaires for any changes in mental health and quality of life include PSQI, ESS, ISI, SHI, RSQ-W, DASS-21, VSI, IBS-QOF and WHO-5. For the bowel symptoms alteration, the DVs are Bristol Stool Chart type and symptoms severity scores collected from Bowel symptom checklist. Differences between- and within-groups in these outcomes will be assessed using mixed-model repeated measures ANOVA, adjusting for gender and age.

All data analyses, other than the microbiome multivariate data, will be conducted using SPSS v25.0 (IBM, 2017). Significance level is set at P = 0.05. Cohen’s effect size will be presented, where appropriate, to provide a measure practical/clinical significance.


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)
WA

Funding & Sponsors
Funding source category [1] 304101 0
University
Name [1] 304101 0
Edith Cowan Univeristy
Address [1] 304101 0
270 Joondalup Drive, Joondalup WA 6027
Country [1] 304101 0
Australia
Primary sponsor type
University
Name
Edith Cowan Univeristy
Address
270 Joondalup Drive, Joondalup WA 6027
Country
Australia
Secondary sponsor category [1] 304316 0
None
Name [1] 304316 0
Address [1] 304316 0
Country [1] 304316 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304589 0
ECU’s Human Research Ethics Committee (HREC)
Ethics committee address [1] 304589 0
Edith Cowan University, 270 Joondalup Drive, Joondalup WA 6027
Ethics committee country [1] 304589 0
Australia
Date submitted for ethics approval [1] 304589 0
25/09/2019
Approval date [1] 304589 0
06/12/2019
Ethics approval number [1] 304589 0
2019-00619-YAN

Summary
Brief summary
This study will examine the effect of Fibre-fix (dietary fibre supplement) on the human gut microbiome and faecal metabolites of people with Irritable Bowel Syndrome (IBS) who consume a diet low in fermentable oligosaccharide, disaccharides, monosaccharides and polyols (FODMAP). A low FODMAP diet reduces the intake of fermentable fibres, leading to insufficient fermentation by the gut microbiota. This can thereby reduce the production of short chain fatty acids (SCFA, e.g. butyrate) in the large intestine and influence on modulation of sleep and mental health.

A randomized double-blind placebo controlled study design is proposed to examine whether Fibre-fix supplement, added to an existing low FODMAP diet may help modulate gastrointestinal function, improve markers of sleep and mental health and promote increased quality of life in IBS patients. Participants will provide stool samples, and complete questionnaires about sleep and mental health before and after the 3-week intervention. Gut health biomarkers: faecal microbiome composition, faecal pH and butyrate levels, and alteration of sleep and mental conditions will be examined. A repeated measures ANOVA using the Statistical Package for the Social Sciences (SPSS) version 25.0 will be used to assess the differences between groups after adjustment for confounding variables.

We expect a shift in the diversity of the microbiota and associated increase in the butyrate levels and improvement in general mental health and sleep in those who receive Fibre -fix compared to those who receive control. In addition, the benefits of RS are likely to reduce IBS symptoms and improve gut health whilst on a low FODMAP diet, proposing a long-term dietary solution for those with IBS. The proposed mental health and sleep benefits may have a flow-on effect in terms of lowering the occurrence of other comorbidities, such as depression and work absenteeism which have economic costs, thereby lowering the burden on the healthcare system and reducing healthcare costs for those with IBS.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 97498 0
Miss Ran YAN
Address 97498 0
Edith Cowan University,School of Medical and Health Sciences,
270 Joondalup Drive, Joondalup, 6027, Western Australia
Country 97498 0
Australia
Phone 97498 0
+61404711886
Fax 97498 0
Email 97498 0
r.yan@ecu.edu.au
Contact person for public queries
Name 97499 0
Miss Ran YAN
Address 97499 0
Edith Cowan University,School of Medical and Health Sciences,
270 Joondalup Drive, Joondalup, 6027, Western Australia
Country 97499 0
Australia
Phone 97499 0
+61404711886
Fax 97499 0
Email 97499 0
r.yan@ecu.edu.au
Contact person for scientific queries
Name 97500 0
Prof Amanda Devine
Address 97500 0
Edith Cowan University,School of Medical and Health Sciences,
270 Joondalup Drive, Joondalup, 6027, Western Australia
Country 97500 0
Australia
Phone 97500 0
+61 08 6304 2939
Fax 97500 0
Email 97500 0
a.devine@ecu.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
This is patentable, we disclose it due to commercial confidentiality.
What supporting documents are/will be available?
No other documents available
Summary results
No Results