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Trial registered on ANZCTR


Registration number
ACTRN12618001992291
Ethics application status
Approved
Date submitted
5/12/2018
Date registered
12/12/2018
Date last updated
12/12/2018
Date data sharing statement initially provided
12/12/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The Vaccination Infant Supplementation (VISS) Study - assessing the effect of vitamin D and probiotic supplementation around vaccination on infant's temperature and sleep pattern.
Scientific title
Randomised placebo-controlled trial investigating the effect of 8 weeks supplementation with probiotics and vitamin D around routine childhood immunisation on infant's ear temperature, growth, and sleeping pattern in 4-24 month-old infants.
Secondary ID [1] 296803 0
Nil
Universal Trial Number (UTN)
Trial acronym
VISS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
immune function 310692 0
Condition category
Condition code
Inflammatory and Immune System 309391 309391 0 0
Normal development and function of the immune system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Our study will comprise of a double-blind parallel randomised placebo-controlled trial of 8 weeks duration investigating the effect of vitamin D and probiotic supplementation around routine childhood vaccination on physiological and behavioural pattern in 4-24 month-old infants.
The active treatment group will be allocated to 1000 IU Vitamin D3 liquid supplied with a 0.25ml dropper & 2.3g Probiotic powder mixed in milk (breast milk or formula) daily for 2 months.

Each 2.3 g dose (1 level metric teaspoon) contains a blend of probiotic strains:
6 billion Lactobacillus rhamnosus (GG) organisms (LGG®)
3.75 billion Lactobacillus acidophilus (NCFM) organisms
3.75 billion Bifidobacterium lactis (Bi-07) organisms

The routine childhood vaccination - including Infanrix hexa and Prevenar 13 - will be scheduled in middle (week 4) of the 8 week supplementation regime. Supplementation will commence 4 weeks prior to vaccination (week 0) and continue 4 weeks after vaccination (week 8).

Compliance will be assessed by return of supplements, as well as diary entries.

Intervention code [1] 313094 0
Treatment: Other
Comparator / control treatment
The Placebo group will be allocated to colour and odour-matched 0.25 ml placebo liquid and 1 metric spoon of placebo powder daily for 8 weeks.
The placebo supplements contain:
a) Placebo liquid contains medium-chain-length triglycerides
b) Placebo powder contains maize maltodextrin
Control group
Placebo

Outcomes
Primary outcome [1] 308348 0
Tympanic ear temperature
using an infrared standard calibrated thermometer - same brand for all participants
Timepoint [1] 308348 0
Daily 0-8 weeks at 7pm
Secondary outcome [1] 354678 0
sleep/cry pattern
diary provided for hourly recording
other symptoms to be recorded, including colds, mouth ulcers, rashes
Timepoint [1] 354678 0
Daily 0-8 weeks
Secondary outcome [2] 354679 0
weight using calibrated infant balance scales at clinic
Timepoint [2] 354679 0
0, 4, 8 weeks
Secondary outcome [3] 354750 0
infant growth: composite measure length and head circumference using infantometer (length) and tape (hc) at clinic
Timepoint [3] 354750 0
0,4,8 weeks
Secondary outcome [4] 354752 0
carer's mood/stress: composite measure
indirect measure of infant's health
by validated Bond-Lader Questionnaire
Timepoint [4] 354752 0
0,4,8 weeks
Secondary outcome [5] 354753 0
carer's sleep
indirect measure of infant's health
diary provided
Timepoint [5] 354753 0
Daily 0-8 weeks

Eligibility
Key inclusion criteria
Group 1 (preferred): Infants who have not yet been immunised (age range: 4-24 months).
Group 2: Infants who have been immunised (age range: 4-24 months).
Parents have agreed to have their child immunised.
Normal infant growth as per WHO growth charts
No tympanic temperature > 38 degrees Celsius in the preceding 4 weeks prior to immunisation
Infants currently breastfed (e.g. exclusively or breast and formula fed)
Infants currently not taking supplements (Vitamin D and/or probiotics)
Infants who will remain in the same routine with primary carers for the 2 month study period
Minimum age
4 Months
Maximum age
24 Months
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Infant has any severe allergies (particularly corn or maize products, as probiotics and placebo powder contains maltodextrin)
Infant has a disease that lowers their immunity (ie. leukaemia, cancer, HIV/AIDs)
Infant is having treatment that lowers immunity (ie. steroids, immunotherapy, chemotherapy)
Infant’s mother is receiving highly immunosuppressive therapy (ie. biological disease modifying anti-rheumatic drugs (bDMARDs)
Infant has had an immunoglobulin injection, received any blood products or blood transfusion)
Infant has had a past history of Guillain-Barre syndrome
Infant has a chronic illness
Infant has a bleeding disorder
Infant is ATSI (Aboriginal Torres Strait Islander)
Infant does not have functional spleen
Infant lives with someone who is immunocompromised (ie. leukaemia, cancer, HIV/AIDS, chemotherapy)

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)
Active and placebo drops and powder will be packaged and labelled offsite in identical numbered containers by the manufacturing company. Patients, as well as doctors and investigators will be blinded to the group allocation. Blinding success of patients will be evaluated at the end of the trial by questionnaire.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computer-generated permuted block randomisation schedule prepared by a researcher not involved in patient recruitment and data collection will be used to allocate patients to the active or placebo groups.
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
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Sample size & Justification
A sample size of 50 participants: Active group: Vit D + probiotic (n=25); Placebo group (n=25) suggested for this pilot study to obtain baseline values and variance for a larger study.

Analysis
Analyses will be performed using SPSS (PASW version 18). Statistical significance will be set at p<0.05. Between-group differences will be analysed by ANOVA comparing data after vaccination at 4 weeks (mean of daily data 4-8 weeks incl temperature, sleep/cry, carer sleep; or infant weight/growth data or carer mood data at 8 weeks) to data before vaccination (mean of daily data 0-4 weeks; or at 0 and 4 weeks).

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)
VIC
Recruitment postcode(s) [1] 25084 0
3122 - Hawthorn
Recruitment postcode(s) [2] 25085 0
3123 - Hawthorn East
Recruitment postcode(s) [3] 25086 0
3124 - Camberwell

Funding & Sponsors
Funding source category [1] 301377 0
Other Collaborative groups
Name [1] 301377 0
National Institute of Integrative Medicine
Address [1] 301377 0
NIIM
21 Burwood Rd
Hawthorn, VIC 3122
Country [1] 301377 0
Australia
Funding source category [2] 301407 0
Commercial sector/Industry
Name [2] 301407 0
Metagenics
Address [2] 301407 0
741 Nudge Road
Northgate, QLD 4013
Country [2] 301407 0
Australia
Primary sponsor type
Individual
Name
AProf Dr Karin Ried
Address
NIIM
21 Burwood Rd
Hawthorn, VIC 3122
Country
Australia
Secondary sponsor category [1] 301045 0
None
Name [1] 301045 0
Address [1] 301045 0
Country [1] 301045 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302115 0
National Institute of Integrative Medicine Human Research Ethics Commitee
Ethics committee address [1] 302115 0
21 Burwood Rd
Hawthorn VIC 3122
Ethics committee country [1] 302115 0
Australia
Date submitted for ethics approval [1] 302115 0
23/10/2018
Approval date [1] 302115 0
28/11/2018
Ethics approval number [1] 302115 0
0047E_2018

Summary
Brief summary
Evidence shows that Vitamin D and probiotic supplementation has a beneficial effect on a child’s immune system.

This randomised placebo controlled parallel trial aims to examine the effect of 2-month supplementation with Vitamin D and probiotics on selected physiological and behavioural responses in an infant group at time of their first routine childhood immunisation. This project will assess daily temperature and sleep pattern over two months, and growth, weight at three physician appointments, 4 weeks prior, at the time of vaccination, and 4 weeks after enrolment.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 89162 0
A/Prof Karin Ried
Address 89162 0
NIIM
21 Burwood Rd
Hawthorn VIC 3122
Country 89162 0
Australia
Phone 89162 0
+61 3 9912 9545
Fax 89162 0
Email 89162 0
karinried@niim.com.au
Contact person for public queries
Name 89163 0
A/Prof Karin Ried
Address 89163 0
NIIM
21 Burwood Rd
Hawthorn VIC 3122
Country 89163 0
Australia
Phone 89163 0
+61 3 9912 9545
Fax 89163 0
Email 89163 0
karinried@niim.com.au
Contact person for scientific queries
Name 89164 0
A/Prof Karin Ried
Address 89164 0
NIIM
21 Burwood Rd
Hawthorn VIC 3122
Country 89164 0
Australia
Phone 89164 0
+61 3 9912 9545
Fax 89164 0
Email 89164 0
karinried@niim.com.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
individual participant data will remain anonymous, only summary data will be shared
What supporting documents are/will be available?
Study protocol
Informed consent form
Ethical approval
How or where can supporting documents be obtained?
Type [1] 626 0
Study protocol
Citation [1] 626 0
Link [1] 626 0
Email [1] 626 0
Other [1] 626 0
Type [2] 627 0
Informed consent form
Citation [2] 627 0
Link [2] 627 0
Email [2] 627 0
Other [2] 627 0
Type [3] 628 0
Ethical approval
Citation [3] 628 0
Link [3] 628 0
Email [3] 628 0
Other [3] 628 0
Summary results
No Results