Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001263189
Ethics application status
Approved
Date submitted
12/08/2019
Date registered
12/09/2019
Date last updated
29/09/2024
Date data sharing statement initially provided
12/09/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised controlled trial of antibiotic therapy in functional dyspepsia with and without non constipation irritable bowel syndrome
Scientific title
A randomised controlled trial of antibiotic therapy on gastrointestinal and psychological symptoms and tissue bacterial density in functional dyspepsia with and without non constipation irritable bowel syndrome
Secondary ID [1] 298999 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Functional dyspepsia 314007 0
Condition category
Condition code
Oral and Gastrointestinal 312396 312396 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
Rifaximin (550g) 1 capsule twice a day for 14 days.

Adherence will be monitored by drug tablet return
Intervention code [1] 315268 0
Treatment: Drugs
Comparator / control treatment
The placebo will be a capsule filled with an inert substance made up of maize starch and pregelatinised maize starch
Control group
Placebo

Outcomes
Primary outcome [1] 321031 0
Gastrointestinal Symptom Score (GIS)
Timepoint [1] 321031 0
Pre treatment and at 6 weeks from the start of treatment
Primary outcome [2] 321032 0
Nepean Dyspepsia Index (NDI)
Timepoint [2] 321032 0
Pre treatment and 6 weeks after the start of treatment
Primary outcome [3] 321033 0
Symptom response to a nutrient challenge test

The nutrient challenge test is a standardised test of sensory function.

The test has been published
Haag S, Senf W, Tagay S, Heuft G, Gerken G, Talley NJ, Holtmann G. Is there any association between disturbed gastrointestinal visceromotor and sensory function and impaired quality of life in functional dyspepsia?. Neurogastroenterology & Motility. 2010 Mar;22(3):262-e79.
Timepoint [3] 321033 0
Pre treatment and 6 weeks after the start of treatment
Secondary outcome [1] 373748 0
Density of bacterial colonisation of mucosal biopsies obtained from the 2nd part of the duodenum using the Brisbane Asceptic Biopsy device
Timepoint [1] 373748 0
Pre treatment and 6 weeks after the start of treatment
Secondary outcome [2] 373749 0
Anxiety and depression from the Hospital Anxiety and Depression scale
Timepoint [2] 373749 0
Pre treatment and 6 weeks after the start of treatment
Secondary outcome [3] 373750 0
Blood samples for immune markers as an exploratory outcome
Timepoint [3] 373750 0
Pre treatment and 6 weeks after the start of treatment
Secondary outcome [4] 374139 0
Stool samples for immune markers as an exploratory outcome
Timepoint [4] 374139 0
Pre treatment and 6 weeks after the start of treatment
Secondary outcome [5] 374622 0
Blood sample for microbiome markers as an exploratory outcome
Timepoint [5] 374622 0
Pre treatment and 6 weeks after the start of treatment
Secondary outcome [6] 374623 0
Stool sample for microbiome markers as an exploratory outcome
Timepoint [6] 374623 0
Pre treatment and 6 weeks after the start of treatment

Eligibility
Key inclusion criteria
Patients with a diagnosis of functional dyspepsia (Rome IV criteria) with a negative diagnostic work-up for organic disease and with and without non- constipation irritable bowel syndrome. Patients with H. pylori without visible other structural lesions will be included for assessment.
Minimum age
18 Years
Maximum age
90 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.

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
The design is a prospective, randomized, double blind longitudinal placebo controlled trial with potential response modifiers and outcome parameters taken at 6 weeks from the start of treatment.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Statistical Analyses:
Aims: This study aims to determine in a randomized, double blind trial in patients with FD with and without non-constipation irritable bowel syndrome the effects of antibiotic therapy on a) gastrointestinal symptoms; meal related quality of life (QoL) and the symptom response to a standardised nutrient challenge (active therapy is superior to placebo); b) assess the effects of antibiotic therapy and presence or absence of a concomitant H. pylori infection (presence of H. pylori modifies the treatment effect); c) determine the link between response to therapy and the bacterial load in tissue samples obtained using the Brisbane Aseptic Biopsy Device (the bacterial density is correlated with the overall response to antibiotic therapy); d) determine the role of anxiety and depression (as measured by the Hospital Anxiety and Depression Scale (psychiatric comorbidities are associated with poor treatment response) as modulators of response to treatment (e) determine the link between response to therapy and immunological and microbiome markers

Hypothesis (a): This hypothesis involves contrasts among therapeutic groups (antibiotics vs. placebo). Contrasts will be evaluated at the 0.05 (two-tailed) level of statistical significance. The outcome variables will be symptoms (GIS), quality of life (NDI, SAGIS) and sensory function (as determined by the standardised nutrient challenge Even though randomization should ensure that the proportion of H. pylori positive patients is the same in each group, the H. pylori status will be included as a covariate. In the case of non-Normally distributed outcomes, statistical inference will be based on the nonparametric bootstrap. If antibiotic therapy is found to have a significant effect, outcome variables in subjects treated with systemic or topical antibiotics will be compared and the multiple comparisons will be accounted for using the method of Hochberg and Benjamini. Hypothesis (b-e): These hypotheses will utilise the same statistical model as for hypothesis (a) but will include the interaction between randomized group and H. pylori status (b), the density of bacteria colonising, (c) the duodenal mucosa and (d) the presence absence/severity of psychiatric comorbidities (anxiety and depression). The statistical interaction will evaluate modification of the group contrasts by H. pylori status, bacterial density and the presence/absence of anxiety/depression. The sample size proposed will provide statistical power 0.8 at the 0.05 level of statistical significance for an effect size 0.7 (Cohen’s d).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
23/09/2019
Actual
21/11/2020
Date of last participant enrolment
Anticipated
30/01/2025
Actual
Date of last data collection
Anticipated
30/03/2025
Actual
Sample size
Target
100
Accrual to date
70
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 14520 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 27532 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 27534 0
4102 - Buranda

Funding & Sponsors
Funding source category [1] 303536 0
Hospital
Name [1] 303536 0
Princess Alexandra Hospital
Country [1] 303536 0
Australia
Primary sponsor type
Hospital
Name
Princess ALexandra Hospital
Address
Princess Alexandra Hospital
Department of Gastroenterology and Hepatology
199 Ipswich Rd
Woolloongabba QLD 4102
Country
Australia
Secondary sponsor category [1] 303604 0
None
Name [1] 303604 0
Address [1] 303604 0
Country [1] 303604 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304063 0
Metro South HREC
Ethics committee address [1] 304063 0
Ethics committee country [1] 304063 0
Australia
Date submitted for ethics approval [1] 304063 0
13/09/2018
Approval date [1] 304063 0
28/11/2018
Ethics approval number [1] 304063 0
HREC/2018/QMS/46338

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 95694 0
Prof Gerald Holtmann
Address 95694 0
Department of Gastroenterology & Hepatology
Princess Alexandra Hospital
199 Ipswich Rd
Woolloongabba QLD 4102
Country 95694 0
Australia
Phone 95694 0
+61 07 31767792
Fax 95694 0
61 07 3176 5111
Email 95694 0
[email protected]
Contact person for public queries
Name 95695 0
Gerald Holtmann
Address 95695 0
Department of Gastroenterology & Hepatology
Princess Alexandra Hospital
199 Ipswich Rd
Woolloongabba QLD 4102
Country 95695 0
Australia
Phone 95695 0
+61 07 31767792
Fax 95695 0
61 07 3176 5111
Email 95695 0
[email protected]
Contact person for scientific queries
Name 95696 0
Gerald Holtmann
Address 95696 0
Department of Gastroenterology & Hepatology
Princess Alexandra Hospital
199 Ipswich Rd
Woolloongabba QLD 4102
Country 95696 0
Australia
Phone 95696 0
+61 07 31767792
Fax 95696 0
61 07 3176 5111
Email 95696 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
No additional documents have been identified.