Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616001162404
Ethics application status
Approved
Date submitted
22/08/2016
Date registered
26/08/2016
Date last updated
9/04/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Comparing clinical symptoms and bacterial features in irritable bowel syndrome (IBS) patients with and without small intestine bacterial overgrowth (SIBO).
Scientific title
Comparing clinical symptoms and features of the microbiome and metabolome in diarrhoea predominant and mixed irritable bowel syndrome (IBS) patients with and without small intestine bacterial overgrowth (SIBO).
Secondary ID [1] 289979 0
None
Universal Trial Number (UTN)
U1111-1186-5261
Trial acronym
Linked study record
ACTRN12616001149459

Health condition
Health condition(s) or problem(s) studied:
Irritable bowel syndrome (IBS) 299985 0
Condition category
Condition code
Oral and Gastrointestinal 299878 299878 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Participants will be screened for small intestine bacterial overgrowth (SIBO) using a glucose breath test. Before consuming a 75g of glucose in 200ml of water the participants will provide a breath sample. They will then provide breath samples every 15 minutes for 2 hours. If they have a rise of >=12 ppm of either hydrogen or methane from baseline this will be diagnosed as SIBO.

Participants will be seen for one 2 hour session with no follow for those without SIBO. Those with SIBO will be part of the associated randomised control trial.
Intervention code [1] 295674 0
Not applicable
Comparator / control treatment
Participants with no evidence of SIBO and healthy controls.
Control group
Active

Outcomes
Primary outcome [1] 299355 0
Comparing symptom severity as measured on the IBS symptom severity scoring system (Francis 1997) between those with and without small intestine bacterial overgrowth.
Timepoint [1] 299355 0
Baseline
Secondary outcome [1] 326908 0
Comparing IBS related quality of life (Patrick 1998) between those with and without small intestine bacterial overgrowth.

Patrick DL, Drossman DA, Frederick IO, DiCesare J, Puder KL. Quality of life in persons with irritable bowel syndrome: development and validation of a new measure. Digestive diseases and sciences. 1998;43(2):400-11.
Timepoint [1] 326908 0
Baseline
Secondary outcome [2] 326909 0
Comparing nutritional intake of IBS patients with and without small intestine bacteria overgrowth and healthy controls (Diet history questionnaire version 2)
Timepoint [2] 326909 0
Baseline
Secondary outcome [3] 326910 0
Comparing the colonic microbiome of IBS patients with and without small intestine bacteria overgrowth and healthy controls. Stool samples will be stored at -80C until the DNA is extracted. DNA will be extracted using the powersoil kit. The V4 region of the 16 S rRNA gene will be amplified. DNA will be sequenced on the Ilumina platform. Data will be analysed using compositional data (CoDa) approaches (Gloor 2016) on R statistical programme. Specifically the ALDEx2 package will be used. Data will be presented as bi-plots, bar charts, dendograms and heat maps as appropriate.
Timepoint [3] 326910 0
Baseline
Secondary outcome [4] 326911 0
Comparing the metabolome of IBS patients with and without small intestine bacterial overgrowth and healthy controls. Urine samples will be stored at -80C until analysis is undertaken. Liquid chromatograpy (LC/MS) and gas chromatography (GC/MS) will be used to identify small molecules present. Data will be analysed using compositional data (CoDa) approaches (Gloor 2016) on R statistical programme. Specifically the ALDEx2 package will be used. Data will be presented as bi-plots, bar charts, dendograms and heat maps as appropriate.
Timepoint [4] 326911 0
Baseline

Eligibility
Key inclusion criteria
Participants with IBS (D) or IBS (M) according to Rome III criteria who are fluent in English. Healthy controls are female and male, aged 18-65 with no gastrointestinal physiology and fluent in English.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
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
Screening
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
For the clinical trial we calculated that 66 participants were required. For the power calculation it was decided that a difference of 100 points on the IBS Symptom Severity Scoring System (IBS SS) would be a strong measure of clinical significance. This was based on the original paper describing the development of the IBS SS by Francis (1997). In this paper the mean for those with mild IBS was 133 (s.d 25), moderate was 243 (s.d 33) and severe 372 (s.d 66). Current did not attend rates for a dietetic service are approximately 20% and this figure was used as a proxy for likely drop outs. An alpha (p value) of 0.05 was selected with 80% power. It was calculated based on these numbers that 33 participants would be needed in each group. Approximately 1 in 4-5 people with IBS have SIBO when using the glucose breath test as a substrate for the test. Therefore to get 66 participants for the intervention we are likely to need to screen about 300.

For continuous variables in the symptom severity scoring system and the quality of life questionnaire students' ttests will be used to compare those with and without small intestine bacteria overgrowth. For categorical variables on the symptom severity scoring system chi squared tests will be used.

Student ttests will be used to compare nutrient intake between the two groups (from the diet history questionnaire.)

The microbiome and metabolomics data will be analysed using compositional data (CoDa) analysis methods (Gloor Ann Epidemiol. 2016;26(5):322-9.). This analysis will be done on the R statistics platform. Data will be presented in compositional biplots, bar charts of abundance, phylogenetic trees and heatmaps as appropriate

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
The study co-ordinator had to return to New Zealand.
Date of first participant enrolment
Anticipated
Actual
19/04/2016
Date of last participant enrolment
Anticipated
29/09/2017
Actual
1/06/2017
Date of last data collection
Anticipated
13/08/2017
Actual
1/09/2017
Sample size
Target
220
Accrual to date
Final
114
Recruitment outside Australia
Country [1] 8116 0
Canada
State/province [1] 8116 0

Funding & Sponsors
Funding source category [1] 294352 0
University
Name [1] 294352 0
University of Otago
Country [1] 294352 0
New Zealand
Primary sponsor type
University
Name
Dunedin School of Medicine, University of Otago
Address
First Floor, Dunedin Hospital
Great King Street
Dunedin 9016
Country
New Zealand
Secondary sponsor category [1] 293190 0
University
Name [1] 293190 0
GutHealthNetwork, University of Otago
Address [1] 293190 0
Department of Medicine,
9th Floor, Dunedin Hospital
Great King Street
Dunedin 9016
Country [1] 293190 0
New Zealand
Secondary sponsor category [2] 293191 0
Charities/Societies/Foundations
Name [2] 293191 0
NZ Society of Gastroenterology
Address [2] 293191 0
NZSG Secretariat
NZ Society of Gastroenterologist Secreriat
Anna Pears
4th Floor, RACP College Office
99 The Terrace
PO Box 10-601
Wellington 6143
Country [2] 293191 0
New Zealand
Other collaborator category [1] 279168 0
Individual
Name [1] 279168 0
Adam Rahman
Address [1] 279168 0
St Joseph's Health Care London
268 Grosvenor St
London
Ontario
N6A 4V2
Country [1] 279168 0
Canada

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295769 0
Western University Health Science Research Ethics Board
Ethics committee address [1] 295769 0
Western University
Research Support Services Building Rm 5150
1393 Western Rd
London
Ontario
N6G 1G9
Ethics committee country [1] 295769 0
Canada
Date submitted for ethics approval [1] 295769 0
11/11/2015
Approval date [1] 295769 0
27/11/2015
Ethics approval number [1] 295769 0

Summary
Brief summary
The data for this observational study comparing the clinical characteristics and features of the microbiome is being collected at the screening phase of ACTRN12616001149459

In 371306 participants with diarrhoea predominant IBS and mixed type IBS are being screened for small intestine bacterial overgrowth (SIBO). 75g of glucose in 200ml of water is being provided as the test substrate. Prior to adminisitration of the glucose solution and every 15 minutes after consuming the test substrate for 2 hours participants are providing a breath sample. The breath sample is being analysed for hydrogen and methane. For participants with a rise of => than 12 ppm in either gas from baseline are defined as haing SIBO.

In this observational study we are aiming to see whether there is a diference in clinical characteristics and microbiome features between those with and without SIBO.

Our hypothesis is that the clinical characteristics of those with and without SIBO will differ. Secondly we hypothesise that there will be differences in the products produced by the bacteria (detected in the urinary metabolome).

Prior to attending the screening survey participants will complete 8 surveys on line and they will provide a stool and a urine sample. The questionnaires they will complete are a demographic questionnaire, a simple health questionnaire, the IBS symptom severity scoring system (Francis 1997), and IBS quality of life questionnaire (Drossman 1998). the physical activity adult questionnaire (Garriguet 2015), the hospital anxiety and depression index (Zigmond 1983) and a foods avoided questionnaire and the diet history questionnaire version 2 (http://epi.grants.cancer.gov/dhq2/).

Faecal and urine samples will be stored at -80C until they are analysed. Faecal samples will be analysed for the bacteria present (in the colon) and urine samples will be analysed to see what the bacteria have been doing.
Trial website
Not applicable
Trial related presentations / publications
None as yet
Public notes

Contacts
Principal investigator
Name 68414 0
A/Prof Michael Schultz
Address 68414 0
Department of Medicine
9th Floor, Dunedin Hospital
Great King Street
Dunedin Central
Dunedin 9016
Country 68414 0
New Zealand
Phone 68414 0
+64 3 474 0999
Fax 68414 0
Email 68414 0
[email protected]
Contact person for public queries
Name 68415 0
Ms Ruth Harvie
Address 68415 0
c/- the Canadian centre for the human microbiome and probiotics
Lawson Research Institute
268 Grosvenor St
London
Ontario
N6A 4V2
Country 68415 0
Canada
Phone 68415 0
+1 519 317 2384
Fax 68415 0
Email 68415 0
[email protected]
Contact person for scientific queries
Name 68416 0
A/Prof Michael Schultz
Address 68416 0
Department of Medicine
9th Floor, Dunedin Hospital
Great King Street
Dunedin Central
Dunedin 9016
Country 68416 0
New Zealand
Phone 68416 0
+64 3 474 0999
Fax 68416 0
Email 68416 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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