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Trial registered on ANZCTR


Registration number
ACTRN12623000353695
Ethics application status
Approved
Date submitted
10/03/2023
Date registered
5/04/2023
Date last updated
31/10/2024
Date data sharing statement initially provided
5/04/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised controlled trial of faecal microbiota transplantation versus placebo in patients who are non -responders to the low FODMAP diet.
Scientific title
: A randomised controlled trial of the effect of faecal microbiota transplantation versus placebo on symptom severity for low FODMAP diet non-responder IBS patients
Secondary ID [1] 309176 0
nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Irritable bowel syndrome 329310 0
Condition category
Condition code
Oral and Gastrointestinal 326255 326255 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
All participants will be administered the low FODMAP diet prior to the faecal microbiota transplantation. If there is no improvement in IBS-SSS score post low FODMAP then participants will enter randomisation into FMT vs placebo.

low FODMAP diet
- will be administered by a qualified dietician
- adherence will be assessed through the use of a food diary with weekly reviews by the dietician over 3 weeks.

Faecal microbiota transplantation
- this will be administered via a single 60ml rectal retention enema in one clinic visit
- one donor will be used for each participant
- adherence to FMT will be 100% as it is administered by the study investigator and the subject will be monitored for 30 minutes

Only participants who do not improve on the low Fodmap diet will be invited to participate in the sub study investigating additional cognitive outcomes. Participants in the substudy will be subject to the same intervention as the overarching trial, i.e. being randomised to receive a single dose of placebo or FMT. Substudy participants will only be asked to fill out additional questionnaires and cognitive tests at baseline and follow-up visits, while intervention or study duration/number of visits does not differ between substudy and overarching trial participants.
20 participants will be invited to take part in the substudy. The time needed for cognitive tests and additional questionnaires will add another 60 minutes to each study visit for participants in the substudy. This results in a total study visit time of 80 minutes at baseline and four follow-up visits for substudy-participants, as opposed to a study visit time of 20 minutes for participants of the overarching trial.


Intervention code [1] 325623 0
Treatment: Other
Comparator / control treatment
Placebo controlled - glycerol and saline (4:1 ratio), food coloring (3ml on 1L) and 5g fibre (2g apple fibre, 3g inulin) on 1 litre solution
Control group
Placebo

Outcomes
Primary outcome [1] 334129 0
Irritable Bowel Syndrome Symptom Score
Timepoint [1] 334129 0
baseline, 1 month, 3 months, 6 months and 12 months post-intervention
Secondary outcome [1] 419437 0
IBS-Quality of Life questionnaire
Timepoint [1] 419437 0
baseline, 1 month, 2 months, 6 months, and 12 months post-intervention
Secondary outcome [2] 419609 0
Shotgun metagenomic sequencing on stool samples.
Timepoint [2] 419609 0
baseline, 1 month, 3 months, 6 months, and 12 months post-intervention
Secondary outcome [3] 419610 0
Cognition function via University of Cambridge, the Cambridge Neuropsychological Test Automated Battery (CANTAB) for substudy participants only
Timepoint [3] 419610 0
1 - month, 3-month, 6-month and 12-month post transplant
Secondary outcome [4] 441181 0
Depression, assessed via the Depression, Anxiety and Stress Scale (DASS) by Lovibond, 1995, assessed in substudy participants only.
Timepoint [4] 441181 0
Secondary outcome [5] 441182 0
Depression, assessed via the Depression, Anxiety and Stress Scale (DASS) by Lovibond, 1995, assessed in substudy participants only.
Timepoint [5] 441182 0
baseline, 1 month, 3 months, 6 months, and 12 months post-intervention
Secondary outcome [6] 441183 0
physiological markers derived from blood samples:
pro-inflammatory cytokines via enzyme-linked immunosorbent assay (ELISA) on plasma samples, tryptophan metabolites and short chain fatty acids (SCFA) using liquid chromatography-mass spectrometry on plasma samples. These physiological markers will only be assessed in substudy participants.
Timepoint [6] 441183 0
baseline, 1 month, 3 months, 6 months, and 12 months post-intervention
Secondary outcome [7] 441184 0
physiological markers derived from blood samples:
pro-inflammatory cytokines via enzyme-linked immunosorbent assay (ELISA) on plasma samples, tryptophan metabolites and short chain fatty acids (SCFA) using liquid chromatography-mass spectrometry on plasma samples. These physiological markers will only be assessed in substudy participants.
Timepoint [7] 441184 0
baseline, 1 month, 3 months, 6 months, and 12 months post-intervention
Secondary outcome [8] 441185 0
Anxiety, assessed via the Depression, Anxiety and Stress Scale (DASS) by Lovibond, 1995 assessed in substudy participants only.
Timepoint [8] 441185 0
baseline, 1 month, 3 months, 6 months, and 12 months post-intervention
Secondary outcome [9] 441186 0
Anxiety, assessed via the Depression, Anxiety and Stress Scale (DASS) by Lovibond, 1995 assessed in substudy participants only.
Timepoint [9] 441186 0
baseline, 1 month, 3 months, 6 months and 12 months post-intervention
Secondary outcome [10] 441187 0
Stress, assessed via the Depression, Anxiety and Stress Scale (DASS) by Lovibond, 1995 assessed in substudy participants only.
Timepoint [10] 441187 0
baseline, 1 month, 3 months, 6 months and 12 months post-intervention
Secondary outcome [11] 441188 0
Stress, assessed via the Depression, Anxiety and Stress Scale (DASS) by Lovibond, 1995 assessed in substudy participants only.
Timepoint [11] 441188 0
baseline, 1 month, 3 month, 6 months, and 12 months post-intervention

Eligibility
Key inclusion criteria
1. Aged 18 years old or over
2. Diagnosed with irritable bowel syndrome as per ROME IV criteria
3. An outpatient
4. Lack of symptomatic improvement with the low FODMAP diet

Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Presence of systemic disease
2. Pregnant, planning pregnancy or lactating.
3. Having undergone any abdominal surgery, with the exception
of appendectomy, cholecystectomy, caesarean section and hysterectomy.
4. Severe psychiatric disorder, or alcohol or drug abuse.
5. Use of probiotics or treatment with antibiotics within 8 weeks prior to study entry
6. Use of IBS medication within the previous 3 months, with the exception of polyethylene glycol and loperamide.
7. Active gastroenteritis

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)
Simple 1:1 randomisation , central randomisation by phone/fax/computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The method of sequence generation will be generated from a computer software program that generates the random sequence
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
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
7/04/2023
Actual
7/04/2023
Date of last participant enrolment
Anticipated
31/12/2024
Actual
Date of last data collection
Anticipated
31/12/2025
Actual
Sample size
Target
40
Accrual to date
21
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 313374 0
Self funded/Unfunded
Name [1] 313374 0
Country [1] 313374 0
Primary sponsor type
Individual
Name
Vincent Ho
Address
Western Sydney University ·
Narellan Road, Campbelltown New South Wales 2560
Country
Australia
Secondary sponsor category [1] 315139 0
None
Name [1] 315139 0
Address [1] 315139 0
Country [1] 315139 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312591 0
Western Sydney University
Ethics committee address [1] 312591 0
Western Sydney University
Narellan Road, Campbelltown New South Wales 2560
Ethics committee country [1] 312591 0
Australia
Date submitted for ethics approval [1] 312591 0
Approval date [1] 312591 0
05/04/2022
Ethics approval number [1] 312591 0

Summary
Brief summary
On average, only 50% of IBS patients respond to the first-line treatment of low FODMAP diet. The non-responders may have gut microbiome dysbiosis that requires targeted treatment. Recent RCTs have shown improvement in IBS symptoms using faecal microbiota transplantation (FMT) from healthy donors in IBS symptom scores up to 3 months, with the proposed mechanism being the correction of gut dysbiosis, However, there is a lack of studies into the impact of FMT in combined with low FODMAP therapy to optimise the improvement of IBS symptoms.
This study aims to investigate whether the novel therapy of FMT improves IBS symptoms for IBS patients without significant symptom improvement after a low FODMAP diet.
Methods: IBS patients with moderate to severe symptoms will be enrolled into a dietician-led 3 week low FODMAP treatment. The patients who do not have symptomatic improvement will be randomised into receiving FMT or placebo.

Studies suggest that altering microbial composition via FMT might also lead to improvements in cognitive function. Therefore, we will investigate cognitive function at baseline compared to follow-up in a subsample of 20 enrolled participants. In contrast to participants of the overarching clinical trial, sub study participants will undergo additional cognitive testing, which takes around 50 minutes per visit, and will be asked to fill out additional mood and quality of life questionnaires, which will add another 10 minutes to study visits. This result in a total study visit time of 80 minutes for substudy participants, as opposed to 20 minutes for participants of the overarching trial, who will only fill out two questionnaires on IBS-symptom severity. Cognitive function will be assessed via Cambridge Automated Neuropsychological Test Battery (CANTAB), a validated, computer-based, neuropsychological test battery that allows testing for cognitive changes in different cognitive domains, including memory, processing speed, and executive function. To assess the impact of mood and stress on IBS symptom severity, mood will be assess via the Depression, Anxiety and Stress Scale (DASS) and quality of life via IBS-QoL.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 125210 0
Dr Vincent Ho
Address 125210 0
Narellan Rd & Gilchrist Dr, Campbelltown NSW 2560
School of Medicine, Western Sydney University
Country 125210 0
Australia
Phone 125210 0
+61 02 4628 4905
Fax 125210 0
Email 125210 0
[email protected]
Contact person for public queries
Name 125211 0
Vincent Ho
Address 125211 0

Dr Vincent Ho
School of Medicine, Western Sydney University
Narellan Rd & Gilchrist Dr, Campbelltown NSW 2560
Country 125211 0
Australia
Phone 125211 0
+61 02 4628 4905
Fax 125211 0
Email 125211 0
[email protected]
Contact person for scientific queries
Name 125212 0
Vincent Ho
Address 125212 0
Dr Vincent Ho
School of Medicine, Western Sydney University
Narellan Rd & Gilchrist Dr, Campbelltown NSW 2560
Country 125212 0
Australia
Phone 125212 0
+61 02 4628 4905
Fax 125212 0
Email 125212 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


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.