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Trial registered on ANZCTR


Registration number
ACTRN12611001267943
Ethics application status
Approved
Date submitted
6/12/2011
Date registered
12/12/2011
Date last updated
12/12/2011
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Double Blind , Randomised, Placebo Controlled Trial to Determine the Efficacy of the probiotic VSL#3 in Preventing Relapse in Children with Crohn’s Disease – 12-month long term study
Scientific title
For Children with Crohn’s disease, will the probiotic VSL#3 taken over a 12 month period compared to children with Crohn’s disease taking a placebo for 12 months, prevent disease relapse
Secondary ID [1] 273542 0
Nil
Universal Trial Number (UTN)
Nil
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Crohn's disease 279344 0
Condition category
Condition code
Oral and Gastrointestinal 279529 279529 0 0
Crohn's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients will be randomised into either treatment arm

Arm 1 – Active probiotics agent
Patients received the active probiotic agent for the entire 12 month trial period. Standard dosing was 1 probiotic sachet (containing 900 million organisms plus maize starch) taken once daily for 12 months

Arm 2 – Placebo
Patients will receive the placebo for the entire 12 month trial period. Standard dosing was 1 placebo sachet (containing maize starch) taken once daily for 12 months.

Note: the probiotic and placebo sachets were of identical weight (3g)
Intervention code [1] 283855 0
Treatment: Other
Comparator / control treatment
Maize starch (included as filler in probiotic)
Control group
Placebo

Outcomes
Primary outcome [1] 286096 0
Disease relapse as assessed by a Paediatric Crohn's Disease Activity Index (PCDAI) >15
Timepoint [1] 286096 0
Baseline, month 3, month 6, month 9, month 12
Secondary outcome [1] 295124 0
Height will be measured using a calibrated stadiometer. Height measurements will be converted to age appropriate Z scores using Center for Disease Control 2000 values as the reference range. Height Z scores will be compared between the two study arms
Timepoint [1] 295124 0
Time points: Baseline, month 3, month 6, month 9, month 12
Secondary outcome [2] 295125 0
Weight will be measured using calibrated scales and will be converted to age appropriate Z scores using Center for Disease Control 2000 values as the reference range. Weight Z scores will be compared between the two study arms
Timepoint [2] 295125 0
Time points: Baseline, month 3, month 6, month 9, month 12
Secondary outcome [3] 295126 0
Body Mass Index
Timepoint [3] 295126 0
Time points: Baseline, month 3, month 6, month 9, month 12
Secondary outcome [4] 295127 0
Quality of Life questionnaire
Timepoint [4] 295127 0
Time points: Baseline, month 3, month 6, month 9, month 12
Secondary outcome [5] 295128 0
Physicians Global Assessment
Timepoint [5] 295128 0
Time points: Baseline, month 3, month 6, month 9, month 12
Secondary outcome [6] 295130 0
Blood Platelets will be assessed during routine clinical follow-up. Peripheral blood will be collected with blood plateletes measured by standard laboratory tests by the South Eastern Area Laboratory Service.
Timepoint [6] 295130 0
Time points: Baseline, month 3, month 6, month 9, month 12
Secondary outcome [7] 295131 0
Serum albmin will be assessed during routine clinical follow-up. Peripheral blood will be collected with serum albumin measured by standard laboratory tests by the South Eastern Area Laboratory Service.
Timepoint [7] 295131 0
Time points: Baseline, month 3, month 6, month 9, month 12
Secondary outcome [8] 295132 0
Serum C-reactive Protein will be assessed during routine clinical follow-up. Peripheral blood will be collected with Serum C-reactive Protein measured by standard laboratory tests by the South Eastern Area Laboratory Service.
Timepoint [8] 295132 0
Time points: Baseline, month 3, month 6, month 9, month 12
Secondary outcome [9] 295133 0
Blood Erythrocyte Sedimentation Rate will be assessed during routine clinical follow-up. Peripheral blood will be collected with Blood Erythrocyte Sedimentation Rate measured by standard laboratory tests by the South Eastern Area Laboratory Service.
Timepoint [9] 295133 0
Time points: Baseline, month 3, month 6, month 9, month 12
Secondary outcome [10] 295134 0
Faecal S100A12 will be assessed collecting faecal samples during routine clinical follow-up. Faecal S100A12 will be measured using an in-house validated ELISA
Timepoint [10] 295134 0
Time points: Baseline, month 3, month 6, month 9, month 12

Eligibility
Key inclusion criteria
Consenting outpatients
Established Diagnosis of Crohn’s disease
Ceased use of systemic antibiotics or other probiotic of probiotic agents in any form at least four weeks prior to enrolment in study
Minimum age
10 Years
Maximum age
18 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Established diagnosis of ulcerative colitis
Intend to continue concurrent administration of alternative probiotic therapy

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Children attending the Sydney Children’s hospital IBD clinic who meet the enrolment criteria will be invited to participate in the study

Patients will be randomised to a treatment Arm by the pharmacist dispensing the probiotics. The pharmacist will use a randomisation list to randomly assign patients to treatment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The pharmacist will use a random number generator on a computer to generate the randomisation list
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)
Recruitment postcode(s) [1] 4774 0
2031
Recruitment postcode(s) [2] 4775 0
4072

Funding & Sponsors
Funding source category [1] 284329 0
Self funded/Unfunded
Name [1] 284329 0
Address [1] 284329 0
Country [1] 284329 0
Primary sponsor type
Hospital
Name
Sydney Chidlren's hospital
Address
High Street, Randwick
Sydney, NSW, 2031
Country
Australia
Secondary sponsor category [1] 283271 0
None
Name [1] 283271 0
Address [1] 283271 0
Country [1] 283271 0
Other collaborator category [1] 260373 0
Individual
Name [1] 260373 0
Dr Daniel Lemberg
Address [1] 260373 0
Department of Peadiatrics
Sydney Children?s hospital
Randwick, NSW
2031
Daniel.Lemberg@SESIAHS.HEALTH.NSW.GOV.AU
Ph: +61 2 9382 0278
Fax: +61 2 9382 1574
Country [1] 260373 0
Australia
Other collaborator category [2] 260374 0
Individual
Name [2] 260374 0
Dr Rebecca Hill
Address [2] 260374 0
The School of Medicine
University of Qld
Brisbane
St Lucia, QLD
4072
Rj.hill@ uq.edu.au
Ph: +61 7 3365 5351
Fax: +61 7 3346 4684
Country [2] 260374 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286289 0
Human Research Ethics Committee South Eastern Sydney Area Health Service
Ethics committee address [1] 286289 0
Room G71, EBB
Cnr High& Avoca Strs
Randwick NSW 2031
Australia
Ethics committee country [1] 286289 0
Australia
Date submitted for ethics approval [1] 286289 0
Approval date [1] 286289 0
01/05/2003
Ethics approval number [1] 286289 0
1/03/0089

Summary
Brief summary
There is experimental human and animal data to support a role for bacteria and / or bacterial products in the cause of inflammatory bowel disease (IBD), especially Crohn’s disease. Furthermore antibiotics have been shown in some cases to provide beneficial effects in IBD. In the last few years there has been increasing interest in probiotic agents in the treatment of various gastrointestinal conditions. The aims of this trial are to
1) determine the efficacy of probiotic therapy upon clinical parameters in children with IBD
2) determine the efficacy of probiotic therapy upon quality of life parameters in children with IBD
3) define the effects of probiotic therapy in children with IBD upon markers of inflammation both standard and novel
4) define the effects of probiotic therapy in children with IBD upon gut bacteria and
5) to document the tolerance and acceptability of probiotic therapy in children with IBD
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33502 0
Address 33502 0
Country 33502 0
Phone 33502 0
Fax 33502 0
Email 33502 0
Contact person for public queries
Name 16749 0
A/Prof Andrew Day
Address 16749 0
Department of Paediatrics
University of Otago, Christchurch
PO Box 4345, Christchurch Mail Centre
Christchurch 8140
Country 16749 0
New Zealand
Phone 16749 0
+64 3 364 1644
Fax 16749 0
+64 3 378 6355
Email 16749 0
Andrew.day@otago.ac.nz
Contact person for scientific queries
Name 7677 0
A/Prof Andrew Day
Address 7677 0
Department of Paediatrics
University of Otago, Christchurch
PO Box 4345, Christchurch Mail Centre
Christchurch 8140
Country 7677 0
New Zealand
Phone 7677 0
+64 3 364 1644
Fax 7677 0
+64 3 378 6355
Email 7677 0
Andrew.day@otago.ac.nz

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary