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Trial registered on ANZCTR


Registration number
ACTRN12610000350022
Ethics application status
Approved
Date submitted
9/03/2009
Date registered
3/05/2010
Date last updated
25/11/2019
Date data sharing statement initially provided
25/11/2019
Date results information initially provided
25/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of Yakult on fermentation patterns and symptoms in irritable bowel syndrome
Scientific title
Randomised, placebo-controlled trial, followed by open-label treatment and withdrawal phases, of the effect of Yakult on fermentation patterns in patients with functional gut symptoms and an early rise of breath hydrogen after lactulose
Secondary ID [1] 251660 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Irritable bowel syndrome 4439 0
Condition category
Condition code
Alternative and Complementary Medicine 4707 4707 0 0
Other alternative and complementary medicine

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Lactobacillus casei Shirota strain (Yakult)
65 ml once per day during the randomised placebo-controlled phase - duration 6 weeks
Upon completion, subjects will be offered 65 ml per day Yakult for 6 weeks.
During the withdrawal phase (6 weeks), no therapy is given (observation only)
Intervention code [1] 4185 0
Treatment: Other
Comparator / control treatment
Placebo - identical to Yakult, except Lactobacillus is not added. Given 65 ml daily for 6 weeks (randomised controlled phase). No further placebo is used in the subsequent open-label and withdrawal phases.
Control group
Placebo

Outcomes
Primary outcome [1] 5575 0
The proportion of patients altering the time of first rise of breath hydrogen after lactulose to greater than or equal to 75 minutes and/or delaying the rise by 30 minutes from baseline at week 6.
This is assessed by hydrogen breath testing following before and every 15 minutes for 2-3 hours after the ingestion of 15 g lactulose.
Timepoint [1] 5575 0
week 6
Secondary outcome [1] 9388 0
Double-blind phase: the change in time of the first rise in breath hydrogen after lactulose.
This is assessed by hydrogen breath testing following before and every 15 minutes for 2-3 hoursafter the ingestion of 15 g lactulose.
Timepoint [1] 9388 0
Week 6
Secondary outcome [2] 9389 0
Double-blind phase: Proportion of patients altering status of fructose breath test from that prior to entering the study.
This is assessed by hydrogen breath testing following before and every 20 minutes after the ingestion of 35 g lactulose.
Timepoint [2] 9389 0
Week 6
Secondary outcome [3] 9390 0
double-blind phase: The change in gastric emptying time.
This is measured using C-13 acetic acid liquid gastric emptying by assessing breath C-13 every 15 minutes over 240 minutes via the Iris infrared isotope analyser and associated software. It is performed concurrently with the lactulose breath hydrogen test. 100 mg C-13 sodium acetate is added to the lactulose solution
Timepoint [3] 9390 0
week 6
Secondary outcome [4] 9391 0
double-blind phase: The change in visual analogue (VAS) scores for overall and specific gut symptoms for Yakult-treated vs placebo-treated patients,
Timepoint [4] 9391 0
week 6
Secondary outcome [5] 9394 0
The change in visual analogue (VAS) scores for overall and specific gut symptoms for those correcting early rise in breath hydrogen after lactulose (ERBHAL) vs those with continuing ERBHAL
Timepoint [5] 9394 0
week 12
Secondary outcome [6] 264002 0
The change in visual analogue (VAS) scores for overall and specific gut symptoms for those correcting early rise in breath hydrogen after lactulose (ERBHAL) vs those with continuing ERBHAL
Timepoint [6] 264002 0
week 18
Secondary outcome [7] 264003 0
Adverse events.
These will be assessed by diary entries and by direct questioning at 3 weekly visits for 18 weeks of the study; i.e., assessed by history taking and physical examination. Expected adverse events will be exacerbation of irritable bowel syndrome, nausea, and trivial events unrelated to the study medication
Timepoint [7] 264003 0
up to 18 weeks
Secondary outcome [8] 264004 0
The proportion of patients altering the time of first rise of breath hydrogen after lactulose to greater than or equal to 75 minutes and/or delaying the rise by 30 minutes from baseline at week 6.
This is assessed by hydrogen breath testing following before and every 15 minutes for 2-3 hours after the ingestion of 15 g lactulose.
Timepoint [8] 264004 0
Week 12 and week 18
Secondary outcome [9] 264008 0
double-blind phase: The change in visual analogue (VAS) scores for overall and specific gut symptoms for those correcting early rise in breath hydrogen after lactulose (ERBHAL) vs those with continuing ERBHAL
Timepoint [9] 264008 0
week 6

Eligibility
Key inclusion criteria
1. ERBHAL, defined as a rise of breath hydrogen of 10 ppm or greater above baseline breath hydrogen on two consecutive 15-minute samples before 90 minutes following ingestion of lactulose;
2. Irritable bowel syndrome according to Rome III criteria;
3. On no specific medication for irritable bowel syndrome
4. On a stable diet for the four weeks prior to entering the study and during the study;
5. Able to maintain current drug therapy for functional gut symptoms without change in drugs or dose during the study;
6. Able to give written, informed consent
Minimum age
16 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. treatment for greater than two weeks with any probiotic within the previous 3 months;
2. any antibiotic therapy in the previous two months;
3. excessive alcohol intake
4. clinically significant co-morbidity

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)
Subjects identified by study staff. Allocation of treatment determined by schedule off-site
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation by using a randomization table created by a computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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)
VIC

Funding & Sponsors
Funding source category [1] 4632 0
Commercial sector/Industry
Name [1] 4632 0
Yakult Australia Pt Ltd
Address [1] 4632 0
10 Monterey Road
Dandenong Vic 3175
Country [1] 4632 0
Australia
Primary sponsor type
Hospital
Name
Box Hill Hospital
Address
5 Arnold Street,
Box Hill
Vic 3128
Country
Australia
Secondary sponsor category [1] 4176 0
University
Name [1] 4176 0
Monash University
Address [1] 4176 0
Box Hill hospital
5 Arnold Street
Box Hill
Vic 3128
Country [1] 4176 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 6670 0
Eastern Health Research & Ethics Committee
Ethics committee address [1] 6670 0
Box Hill Hospital
5 Arnold Street
Box Hill
Vic 3128
Ethics committee country [1] 6670 0
Australia
Date submitted for ethics approval [1] 6670 0
Approval date [1] 6670 0
13/02/2009
Ethics approval number [1] 6670 0
E61/0809

Summary
Brief summary
Current therapy for irritable bowel syndrome is suboptimal. Recent studies have suggested that small intestinal bacterial overgrowth may be present and that its treatment may have therapeutic benefit. The primary aim is to examine whether the effect of Yakult on a breath hydrogen test feature of bacterial overgorwoth that was seen in the pilot study is reproducible and specific to the study treatment, or just a chance observation. The secondary aims were to define the effect of Yakult on the rate at which the stomach empties, to compare the effects on gut symptoms of Yakult, placebo and Yakult withdrawal, and to examine the association of change in breath test patterns with changes in gut symptoms. In addition, because bacterial overgrowth is said to be causally associated with fructose malabsorption, another aim is to examine the effect of Yakult and the changes in breath test patterns with changes in fructose absorption and malabsorption.
The major study hypotheses are that Yakult corrects small intestinal bacterial overgrowth and that this correction is associated with improvement in symptoms of irritable bowel syndrome
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29367 0
Prof Peter Gibson
Address 29367 0
Monash University / The Alfred Hospital
Department of Gastroenterology
Central Clinical School
Level 6, 99 Commercial Rd
Melbourne VIC 3004
Country 29367 0
Australia
Phone 29367 0
+613 9076 2223
Fax 29367 0
Email 29367 0
peter.gibson@monash.edu
Contact person for public queries
Name 12614 0
Dr CK Yao
Address 12614 0
Department of Medicine
Box Hill Hospital
Box Hill Vic 3128
Country 12614 0
Australia
Phone 12614 0
+61 3 9094 9547
Fax 12614 0
+61 3 9899 9137
Email 12614 0
jacqueline.barrett@med.monash.edu.au
Contact person for scientific queries
Name 3542 0
Dr CK Yao
Address 3542 0
Department of Gastroenterology
Central Clinical School
Monash University & The Alfred Hospital
Melbourne VIC 3004
Country 3542 0
Australia
Phone 3542 0
+613 99030266
Fax 3542 0
+61 3 9899 9137
Email 3542 0
chu.yao@monash.edu

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 other documents available
Summary results
Have study results been published in a peer-reviewed journal?
Yes
Journal publication details
Publication date and citation/details [1] 5848 0
Yao, C. K., Barrett, J. S., Philpott, H., Chung, A. R. T., van Langenberg, D., Garg, M., and Gibson, P. R. ( 2015) Poor predictive value of breath hydrogen response for probiotic effects in IBS. Journal of Gastroenterology and Hepatology, 30: 1731– 1739. doi: 10.1111/jgh.13015.
Other publications
Have study results been made publicly available in another format?
Yes
Results – basic reporting
Results – plain English summary
1. Treatment with Yakult did not seem to improve small intestinal bacteria overgrowth or change the speed of which the stomach empties (i.e. complete digestion).
2. The presence of an early response in breath hydrogen after lactulose is not useful to predict IBS individuals who may respond to probiotic therapy.
3. The 6-week therapy with Yakult did not improve overall IBS symptoms, abdominal pain, bloating, flatulence, satisfaction with stool consistency and tiredness.
4. Satisfaction with stool consistency was significantly reduced after 12-weeks of Yakult therapy compared with the placebo group who received only 6-weeks of Yakult.
5. Fructose malabsorption and symptoms associated with fructose was not improved by ingestion of Yakult even after 12 weeks of treatment.
6. Huge variations in breath test results occurring independently of the treatment given – Yakult or placebo indicate that it is not a reliable tool for measuring malabsorption of simple sugars like fructose.