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Trial registered on ANZCTR


Registration number
ACTRN12616001341415p
Ethics application status
Submitted, not yet approved
Date submitted
11/08/2016
Date registered
26/09/2016
Date last updated
26/09/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
The SynAD study aims to determine if daily treatment with an oral preparation containing healthy bacteria, given together with specific carbohydrates to help them thrive, is effective in reducing severity of atopic dermatitis (AD) in food allergic children aged between 6 months and 3 years.
Scientific title
The SynAD Study: Evaluation of the efficacy of a synbiotic preparation for reducing severity of symptoms of atopic dermatitis in food allergic infants and children.


Secondary ID [1] 289927 0
Nil
Universal Trial Number (UTN)
U1111-1186-4029
Trial acronym
The SynAD Study
Linked study record
No linked study

Health condition
Health condition(s) or problem(s) studied:
Atopic dermatitis 299895 0
Food allergy 299896 0
Condition category
Condition code
Skin 299800 299800 0 0
Dermatological conditions
Diet and Nutrition 299801 299801 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
1. a) The synbiotic preparation UltraBiotic Infant Formula Companion will be administered at a dose of 1.1g twice per day for 12 weeks.
Each 1.1g serve contains
Bifidobacterium bifidum (CUL20) 125 million CFU
Bifidobacterium animalis (CUL34) 2.38 billion CFU
Lactobacillus salivarius (CUL61) 6.25 billion CFU
Lactobacillus paracasei (CUL08)  1.25 billion CFU
Galactoligosaccharides (GOS) 450mg
Fructoligosaccharides (FOS) 100mg

2. Each participant will receive either the synbiotic preparation or the placebo for the entire 12 week study period




Intervention code [1] 295607 0
Treatment: Other
Comparator / control treatment
Micro-crystalline cellulose
Control group
Placebo

Outcomes
Primary outcome [1] 299265 0
Percent change in mean SCORAD score from baseline at week 0 to week 6 and week 12. (SCORAD is a tool used in clinical practice which measures extent and severity of atopic dermatitis)
Timepoint [1] 299265 0
12 weeks after 1st day of randomisation and 1st appointment with with study co-ordinator
Secondary outcome [1] 326691 0
Percent change in mean Infant Dermatitis Quality of Life Score (IDQOL). (IDQOL is designed to assess quality of life in infants and children less than 4 years of age)

Timepoint [1] 326691 0
12 weeks after 1st day of randomisation and 1st appointment with with study co-ordinator
Secondary outcome [2] 326692 0
The amount of topical steroid used.
Parents /guardians of participants will bring the topical steroid creams to be weighed at weeks 0, 6 and 12. The change in weight of the topical steroid cream/ ointments will calculated for each participant at each visit to calculate the amount of topical steroid used. The amount of steroid that is used can be used as a proxy for severity of atopic dermatitis.
Timepoint [2] 326692 0
The amount of topical steroid used will be assessed by weighing the tubes/containers at weeks 0, 6 and 12.
Secondary outcome [3] 326693 0
Change in microbiota composition as measured by analysis of faecal samples at weeks 0 and 12.
Timepoint [3] 326693 0
12 weeks after 1st day of randomisation and 1st appointment with with study co-ordinator
Secondary outcome [4] 326694 0
Change in z-scores for height/length, weight and head circumference. Growth will assessed by comparing height/length, weight and head circumference to reference data on WHO growth charts for participants 0 - 2 years and CDC growth for children over 2 years.
Timepoint [4] 326694 0
12 weeks after 1st day of randomisation and 1st appointment with with study co-ordinator
Secondary outcome [5] 327782 0
Change in microbiota diversity as measured by analysis of faecal samples at weeks 0 and 12.
Timepoint [5] 327782 0
12 weeks after 1st day of randomisation and 1st appointment with with study co-ordinator.

Eligibility
Key inclusion criteria
Age 6 – 36 months
Attending allergy clinic at Lady Cilento Children's Hospital
Have moderate-to-severe atopic dermatitis defined by SCORAD >25
Have at least one food allergy
Minimum age
6 Months
Maximum age
36 Months
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Systemic antibiotics administered within the last 4 weeks. Oral or IV steroids administered within the last 4 weeks. (Inhaled and topical steroids are OK).
If these drugs are necessary during the intervention the trial will be ceased for that participant.
Co-existent chronic disease

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 packages
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation.
Stratification - sex, age (<24 months and >24 months)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
NA
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Based on previous study published [1] it appears that to detect a significant difference in the change in SCORAD index (from baseline to end of study week8 in the paper) between the probiotic group and placebo group with 80% power at a significance level of 5%, a total number of 57 patients in each group would be required.

The calculation is based on the results from Weston et al [1] at week 8.
Details below:
Median change in SCORAD in group probiotic: -18.2
Median change in SCORAD in group probiotic: -10.2
The IQR have been transformed into SD with the usual rule: IQR/1.35=SD but that is making the assumption that the distribution is normal within the groups.

Sample size calculation was based on a two sample t-test to compare a mean difference of 8 (group1-group2). I obtained a required sample size of 52 patients in each group but, as the distribution will probably not be normal, an additional 10% is usually recommended (non-parametric test instead of parametric). Making the final number around 57 per group.

The statistical analysis:

Change in SCORAD across time (from baseline to week 6 and week 12) will be assessed and compared between intervention and placebo groups using a linear mixed model with the main effects being treatment, time and interaction time*treatment, and the patient as a random effect. The effect of the potential covariates such as gender and age will also be taken into consideration in the model.

[1] Weston S et al. Effects of probiotics on atopic dermatitis: a randomised controlled trial. Arch Dis Child 2005;90:892-897

Recruitment
Recruitment status
Not yet recruiting
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)
QLD
Recruitment hospital [1] 6481 0
Lady Cilento Children's Hospital - South Brisbane
Recruitment postcode(s) [1] 14043 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 294293 0
University
Name [1] 294293 0
University of Queensland
Address [1] 294293 0
Children's Nutrition Research Centre
University of Queensland
Centre for Children's Health Research
62 Graham Street
South Brisbane QLD 4101
Country [1] 294293 0
Australia
Primary sponsor type
University
Name
University of Queensland
Address
Children's Nutrition Research Centre
University of Queensland
Centre for Children's Health Research
62 Graham Street
South Brisbane QLD 4101
Country
Australia
Secondary sponsor category [1] 293132 0
None
Name [1] 293132 0
Address [1] 293132 0
Country [1] 293132 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 295721 0
Children’s Health Queensland Hospital and Health Service Human Research Ethics Committee HREC/16/QRCH/265
Ethics committee address [1] 295721 0
Centre for Children's Health Research
62 Graham Street
South Brisbane QLD 4101
Ethics committee country [1] 295721 0
Australia
Date submitted for ethics approval [1] 295721 0
18/07/2016
Approval date [1] 295721 0
Ethics approval number [1] 295721 0
HREC/16/QRCH/265

Summary
Brief summary
The aim of this study is to determine if daily treatment with an oral preparation containing a multi-strain synbiotic is effective in reducing severity of atopic dermatitis (AD) in food allergic children. A synbiotic is a combination of a probiotic and a prebiotic. Probiotics are living microorganisms that, when ingested in adequate amounts, can modulate gut microbiota. Prebiotics are indigestible oligosaccharides that give beneficial bacterial strains a selective advantage to thrive. When pre- and probiotics are given in the same preparation they have a synergistic effect, hence the name synbiotic.

Studies using pre- and probiotics to prevent or treat AD have shown inconsistent results over the last 20 years. A recent meta-analysis of randomised controlled trials has concluded that synbiotics do have a role in the treatment of AD especially multi-strain synbiotics. (Chang et al, 2016)

Infants and children 6 – 36 months who have attended allergy clinic at the Lady Cilento Children’s Hospital (LCCH) with moderate-to-severe atopic dermatitis and at least one food allergy will be eligible for the the SynAD study. Once recruited, families will attend 3 appointments - week 0, 6 and 12 at the Center for Children's Health Research (CCHR) where dietary, growth and skin assessment will occur. Questionnaires assessing food intake and quality of life will be collected at weeks 0 and 12. Stool samples will be collected for analysis for gut microbiota assessment at Weeks 0 and 12. There will be no change to standard care provided at LCCH.

Patients will be randomised into either of two groups: an intervention and a placebo group. All study participants and investigators will be blinded to which intervention each patient is receiving until the end of the study. Families will be provided the intervention (either placebo or multi-strain synbiotic) with instructions on how to administer each day to their infant or child during appointments in week 0 and week 6.

The aim of the study is to see a greater improvement in AD in the intervention compared to placebo group. Improvement in symptoms of AD will be measured by assessing severity of AD and the impact of AD on quality of life using two validated tools:
*Scoring of Atopic Dermatitis (SCORAD) and
*The Infant’s Dermatology Quality of Life Questionnaire (IDQOL)

Chang, Y.S., M.K. Trivedi, and A. Jha, Synbiotics for prevention and treatment of atopic dermatitis - a meta-analysis of randomised clinical trials. JAMA Pediatr, 2016. 170(3): p. 236-242


Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 68230 0
Ms Kathy Beck
Address 68230 0
Children's Nutrition Research Centre
University of Queensland
Centre for Children's Health Research
Level 6
62 Graham Street
South Brisbane, Qld 4101
Country 68230 0
Australia
Phone 68230 0
+61 400310200
Fax 68230 0
Email 68230 0
k.beck1@uq.edu.au
Contact person for public queries
Name 68231 0
Ms Kathy Beck
Address 68231 0
Children's Nutrition Research Centre
University of Queensland
Centre for Children's Health Research
Level 6
62 Graham Street
South Brisbane, Qld 4101
Country 68231 0
Australia
Phone 68231 0
+61 400310200
Fax 68231 0
Email 68231 0
k.beck1@uq.edu.au
Contact person for scientific queries
Name 68232 0
Prof Peter Davies
Address 68232 0
Children's Nutrition Research Centre
University of Queensland
Centre for Children's Health Research
Level 6
62 Graham Street
South Brisbane, Qld 4101
Country 68232 0
Australia
Phone 68232 0
+61 3069 7597
Fax 68232 0
Email 68232 0
ps.davies@uq.edu.au

No information has been provided regarding IPD availability
Summary results
No Results