Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000663550
Ethics application status
Approved
Date submitted
1/04/2024
Date registered
24/05/2024
Date last updated
23/06/2024
Date data sharing statement initially provided
24/05/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Non-antibiotic modulation of small intestinal dysbiosis with oral simethicone as a treatment for patients with disorders of gut-brain interaction: a randomised placebo-controlled trial
Scientific title
Non-antibiotic modulation of small intestinal dysbiosis with oral simethicone as a treatment for patients with disorders of gut-brain interaction: a randomised placebo-controlled trial
Secondary ID [1] 311807 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Disorders of gut brain interaction 333327 0
Condition category
Condition code
Oral and Gastrointestinal 330014 330014 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 will be randomised to receive oral simethicone either 1ml or 2ml for 6 weeks
Adherence will be monitored by IP accountability, drug tablet return.
Intervention code [1] 328254 0
Treatment: Drugs
Comparator / control treatment
2ml liquid placebo (made up of Pregelatanised maize and maize starch, purified water, carboxymethylcellulose sodium, raspberry flavouring, sucralose, methyl hydroxybenzoate USP, propyl hydroxybenzoate USP and glycerol USP)
Control group
Placebo

Outcomes
Primary outcome [1] 337767 0
Gastrointestinal symptoms
Timepoint [1] 337767 0
Pre treatment, 4 and 12 weeks post treatment.

4 weeks post treatment is the primary timepoint
Primary outcome [2] 337768 0
Gastrointestinal symptom intensity
Timepoint [2] 337768 0
Pre treatment, 4 and 12 weeks post treatment.

4 weeks post treatment is the primary timepoint
Primary outcome [3] 337769 0
Density of bacterial colonisation
Timepoint [3] 337769 0
Pre treatment, 4 and 12 weeks post treatment.

4 weeks post treatment is the primary timepoint
Secondary outcome [1] 433234 0
Symptom response to a nutrient challenge test
Timepoint [1] 433234 0
Pre treatment and 4 weeks post treatment.
Secondary outcome [2] 433235 0
Bacterial overgrowth in small intestine
Timepoint [2] 433235 0
Pre treatment and 4 weeks post treatment
Secondary outcome [3] 433236 0
Anxiety
Timepoint [3] 433236 0
Pre treatment, 4 and 12 weeks post treatment.
Secondary outcome [4] 433237 0
Depression
Timepoint [4] 433237 0
Pre treatment, 4 and 12 weeks post treatment.
Secondary outcome [5] 433238 0
Health related Quality of Life
Timepoint [5] 433238 0
Pre treatment, 4 and 12 weeks post treatment.
Secondary outcome [6] 433239 0
Blood samples for immune markers as an exploratory outcome
Timepoint [6] 433239 0
Pre treatment and 4 weeks post treatment
Secondary outcome [7] 433240 0
Stool samples for immune markers as an exploratory outcome
Timepoint [7] 433240 0
Pre treatment and 4 weeks post treatment
Secondary outcome [8] 433241 0
Blood samples for microbiome marker
Timepoint [8] 433241 0
Pre treatment and 4 weeks post treatment
Secondary outcome [9] 433242 0
Stool sample for microbiome marker
Timepoint [9] 433242 0
Pre treatment and 4 weeks post treatment
Secondary outcome [10] 433243 0
Dyspepsia symptoms and health related quality of life
Timepoint [10] 433243 0
Pre treatment, 4 and 12 weeks post treatment.

Eligibility
Key inclusion criteria
1) H. pylori negative patients with a diagnosis of a DGBI (Rome IV criteria) with a negative diagnostic work-up for organic disease.

2) Only patients routinely undergoing gastrointestinal endoscopies for the diagnostic work-up of otherwise unexplained gastrointestinal symptoms will be recruited.

3) Over 18 years of age
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) unsuitable for therapy due to any medical conditions, drug allergies or inability to attend follow-up appointments
2) undergoing psychiatric treatment (e.g., full doses of antipsychotic, anxiolytic or antidepressant medication)
3) insufficient language or literacy skills
4) antibiotic use in the previous 3 months.
5) unable to give informed consent

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)
sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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

Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
Statistical Analyses: Hypothesis (a): This hypothesis contrasts therapeutic groups (placebo vs. all simethicone groups e.g. simethicone 105 mg/1ml TDS vs. and 210 mg/2ml TDS). Contrasts will be based on the general linear model and will be evaluated at the 0.05 (two-tailed) level of statistical significance. The outcome variables will be symptom severity (SAGIS), quality of life (NDI) and system response to standardised nutrient challenge (as determined by the standardised nutrient challenge). In the case of non-normally distributed outcomes, statistical inference will be based on the nonparametric bootstrap. Hypothesis (b & c): These hypotheses will utilise the same statistical model as for hypothesis (a) but will include the interaction between randomized group and (a) the density of bacteria colonising the duodenal mucosa and (b) the presence absence/severity of psychiatric comorbidities (anxiety and depression) and specific symptom patterns (e.g., FD, IBS or FD/IBS overlap). The statistical interaction will evaluate modification of the group contrasts by bacterial density and the presence/absence of anxiety/depression. The sample size of 192 participants (64 participants per group) will provide statistical power 0.8 at the 0.05 level of statistical significance for an effect size 0.6 (Cohen’s d).

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/07/2024
Actual
Date of last participant enrolment
Anticipated
2/02/2026
Actual
Date of last data collection
Anticipated
7/07/2026
Actual
Sample size
Target
192
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 26308 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [2] 26309 0
Logan Hospital - Meadowbrook
Recruitment postcode(s) [1] 42280 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 42281 0
4131 - Meadowbrook

Funding & Sponsors
Funding source category [1] 316144 0
Government body
Name [1] 316144 0
Metro South Hospital and Health Service -Princess Alexandra Hospital Research support Scheme
Country [1] 316144 0
Australia
Primary sponsor type
Government body
Name
Metro South Hospital and Health Service
Address
Country
Australia
Secondary sponsor category [1] 318322 0
None
Name [1] 318322 0
Address [1] 318322 0
Country [1] 318322 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314972 0
Metro South Human Research Ethics Committee
Ethics committee address [1] 314972 0
https://metrosouth.health.qld.gov.au/research/about-us/hrec
Ethics committee country [1] 314972 0
Australia
Date submitted for ethics approval [1] 314972 0
14/03/2024
Approval date [1] 314972 0
24/05/2024
Ethics approval number [1] 314972 0
HREC/2024/QMS/105067

Summary
Brief summary
Disorders of Brain Gut Interaction (DGBIs) are extremely common affecting up to onein three Australians. These conditions are chronic, resulting in reduced quality of life for patients and are responsible for substantial health care utilisation. This is largely due to the fact that routinely available treatments do not provide the required symptom relief and long-term improvement of quality of life. In recent times, small intestinal dysbiosis has been identified as a potential cause for DGBI. Small intestinal bacterial dysbiosis refers to an expansion of unfavorable or harmful bacteria in the small intestinal tract. While antibiotics such as rifaximin are proven to improve symptoms in patients with DGBI, there are concerns in relation to antibiotic resistance and antibiotics are not suitable for long term treatment. Previous data suggest that simethicone can be beneficial in DGBI patients and our recent in-vitro data reveal a suppression of growth of bacteria obtained from the small intestine. Thus, we aim to conduct a randomised placebo-controlled trial to test the
readily available (over the counter) treatment Simethicone as a means to target the imbalance of bacteria lining the small intestine in patients with DGBI.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 133286 0
Prof Gerald Holtmann
Address 133286 0
Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, 199 Ipswich Rd, Woolloongabba QLD 4102
Country 133286 0
Australia
Phone 133286 0
+61 0731767792
Fax 133286 0
Email 133286 0
[email protected]
Contact person for public queries
Name 133287 0
Gerald Holtmann
Address 133287 0
Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, 199 Ipswich Rd, Woolloongabba QLD 4102
Country 133287 0
Australia
Phone 133287 0
+61 0731767792
Fax 133287 0
Email 133287 0
[email protected]
Contact person for scientific queries
Name 133288 0
Gerald Holtmann
Address 133288 0
Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, 199 Ipswich Rd, Woolloongabba QLD 4102
Country 133288 0
Australia
Phone 133288 0
+61 0731767792
Fax 133288 0
Email 133288 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
Only summarised results will be reported. No individual participant data will be available as per ethics requirements.


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
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