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Trial registered on ANZCTR


Registration number
ACTRN12613000368730
Ethics application status
Approved
Date submitted
26/03/2013
Date registered
8/04/2013
Date last updated
10/04/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
ProVac:Probiotic adjuvant to enhance the efficacy of pnemococcal vaccination: A pilot study.
Scientific title
A randomised double blind, placebo-controlled trial to evaluate the efficacy of a probiotic adjuvant in enhancing vaccine immune responses in healthy infants aged 3-7 months.
Secondary ID [1] 281855 0
Nil
Universal Trial Number (UTN)
U1111-1139-0555
Trial acronym
ProVac
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Healthy infant immune response to the PCV13 pneumococcal vaccination 288217 0
Condition category
Condition code
Inflammatory and Immune System 288583 288583 0 0
Normal development and function of the immune system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
To evaluate the adjuvant effect of B.lactis Bi-07 on the immune response to pneumococcal conjugate (PCV13) vaccination in healthy infants.
The probiotic powder is freeze-dried Bifidobacterium Bi-07 and silicon dioxide.The probiotic will be mixed with 10mls of cooled boiled water and administered orally via a syringe. Packaged in 1.0 gram white sachets, 100 per carton. The probiotic will be administered once daily.
Once infants have been recruited, the study period will be 6 months from the first day of treatment (at 4 weeks of age) until 7 months of age which spans the 3-dose PCV13 schedule (at 2,4,6 months).
Compliance to the probiotic treatment will be monitored by a study diary that will completed by the parents/guardians on a daily basis. As this is a pilot study, we will also be able to determine feasibility of compliance during the study period and develop appropriate strategies to maintain this.
Intervention code [1] 286413 0
Treatment: Drugs
Comparator / control treatment
Placebo - sucrose plus silicon dioxide.
The placebo will be given to the control group of infants and will be matched for taste and appearance to Bi-07.
The placebo will be mixed with 10mls of cooled boiled water and administered orally via a syringe packaged in 1.0 gram white sachets, 100 per carton. The placebo will be administered once daily.
Once infants have been recruited, the study period will be 6 months from the first day of treatment (at 4 weeks of age) until 7 months of age which spans the 3-dose PCV13 schedule (at 2,4,6 months).
Control group
Placebo

Outcomes
Primary outcome [1] 288739 0
To examine (a) humoral immune responses including pneumococcal serotype-specific IgG response, following PCV13 vaccination at 3 months of age in study infants.

Humoral antibody response following PCV13 - Serotype-specific IgG levels in plasma will be measured for all PCV13 serotypes using a WHO-recommended ELISA method

Salivary IgA - Serotype-specific IgA levels in saliva will be measured for all PCV13 serotypes using a WHO-recommended ELISA method

Memory B cell response - Pneumococcal-specific memory B cell response will be measured in cultured peripheral blood mononuclear cells (PBMCs) using a validated ELISPOT method
Timepoint [1] 288739 0
At 3 months of age
Primary outcome [2] 288797 0
To examine (a) humoral immune responses including pneumococcal serotype-specific IgG response, following PCV13 vaccination at 7 months of age in study infants.
Humoral antibody response following PCV13 - Serotype-specific IgG levels in plasma will be measured for all PCV13 serotypes using a WHO-recommended ELISA method

Salivary IgA - Serotype-specific IgA levels in saliva will be measured for all PCV13 serotypes using a WHO-recommended ELISA method

Memory B cell response - Pneumococcal-specific memory B cell response will be measured in cultured peripheral blood mononuclear cells (PBMCs) using a validated ELISPOT method
Timepoint [2] 288797 0
At 7 months of age
Secondary outcome [1] 300871 0
To determine the proportion of eligible infants whose parents consent to or decline participation in the pilot study and the number of participants who complete the study to establish feasibility of a larger trial.
Timepoint [1] 300871 0
At 6 weeks from starting recruitment .
At 6 months from starting treatment.
Secondary outcome [2] 300872 0
Compliance of intake of (probiotic/placebo) during the course of the study period will be assessed by parent/guardian diary records and weighing of the returned (probiotic/placebo) tins. Compliance will also be determined by microbiological detection of B.lactis Bi-07 in faecal samples.
Timepoint [2] 300872 0
At 6 months from starting treatment.
Secondary outcome [3] 301013 0
Adverse events potentially associated with probiotic intake (e.g. diarrhoea, abdominal pain, febrile episodes). Biological samples will include blood, faeces, saliva & anterior nasal swabs. Adverse events will be evaluated from entries into the study diary.
Timepoint [3] 301013 0
At the 3 and 6 month study visits. Participants will be instructed to also contact the study nurse in between visits if they are concerned that the probiotic or placebo is causing diarrhoea, abdominal pain or febrile episodes.
Secondary outcome [4] 301022 0
To measure the level of pneumococcal nasopharyngeal colonisation following PCV13 Vaccination and Bi-07 treatment. At 3 months of age in study infants.

Nasopharyngeal carriage - The presence of PCV13 vaccine-type carriage of Streptococcus pneumoniae in the nasopharynx will be measured by traditional microbiological methods including latex agglutination and Quellung.
Timepoint [4] 301022 0
At 3 months of age.
Secondary outcome [5] 301025 0
To measure the level of pneumococcal nasopharyngeal colonisation following PCV13 Vaccination and Bi-07 treatment at 7 months of age in study infants.

Nasopharyngeal carriage - The presence of PCV13 vaccine-type carriage of Streptococcus pneumoniae in the nasopharynx will be measured by traditional microbiological methods including latex agglutination and Quellung.
Timepoint [5] 301025 0
At 7 months of age.
Secondary outcome [6] 301026 0
To measure the antibody function memory B cell responses and salivary IgA responses following vaccination of PCV13 and Bi-07 treatment at 3 months of age in study infants.

Humoral antibody response following PCV13 - Serotype-specific IgG levels in plasma will be measured for all PCV13 serotypes using a WHO-recommended ELISA method

Salivary IgA - Serotype-specific IgA levels in saliva will be measured for all PCV13 serotypes using a WHO-recommended ELISA method

Memory B cell response - Pneumococcal-specific memory B cell response will be measured in cultured peripheral blood mononuclear cells (PBMCs) using a validated ELISPOT method
Timepoint [6] 301026 0
At 3 months of age.
Secondary outcome [7] 301027 0
To measure the antibody function memory B cell responses and salivary IgA responses following vaccination of PCV13 and Bi-07 treatment at 7 months of age in study infants.

Humoral antibody response following PCV13 - Serotype-specific IgG levels in plasma will be measured for all PCV13 serotypes using a WHO-recommended ELISA method

Salivary IgA - Serotype-specific IgA levels in saliva will be measured for all PCV13 serotypes using a WHO-recommended ELISA method

Memory B cell response - Pneumococcal-specific memory B cell response will be measured in cultured peripheral blood mononuclear cells (PBMCs) using a validated ELISPOT method
Timepoint [7] 301027 0
At 7 months of age.

Eligibility
Key inclusion criteria
1) Healthy, term infants (post-delivery) will be recruited from the postnatal maternity ward at the Royal Women's Hospital, Melbourne.
2 )The infant must be 4 weeks of age.
3) The infant must be born via a vaginal birth at 37 weeks or greater gestation.
4) The mother cannot have been on antibiotic treatment 2 weeks prior to delivery.
Minimum age
4 Weeks
Maximum age
7 Months
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1) Mothers who were taking probiotics during pregnancy or are on probiotic supplements.
2) Mothers who have a proven or suspected immunodeficiency.
3) Infants must not have had a probiotic.
4) Infants who have a significant foetal abnormality.
5) Infants who have or a proven or suspected immunodeficiency.
6)Significant maternal illness or disability such that study participation would impose an unacceptable additional burden.
7) Planning or likely to leave the area before the study finishes.

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)
An independent statistician from the Clinical Epidemiology and Biostatistics Unit (CEBU) at the Royal Children's Hospital will be responsible for generating the randomisation schedule. The randomisation schedule will be given to the RCH hospital pharmacy department, who will be responsible for arranging a sequential stock of trial medication, labelled with only the study number and instructions for use.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Block randomisation and an allocation ratio of 1:1 will be used.
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
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
A trial statistician has been appointed by CEBU and will be supervised by Dr katherine Lee. Statistical analysis will follow standard methods for randomised trials and the analysis will be by intention to treat.
Comparisons of proportions of children with NP carriage of PCV13 serotypes will be performed using Fisher's exact test. If data satisfy the test for normality, they will be analysed with Student's two-tailed t-test for significance. Otherwise, data will be analysed with the Mann-Whitney test. A p value of <0.05 will be considered statistically significant.
Given that this is a pilot study there is no formal sample size calculation. The sample size for this pilot study was chosen to be 30 infants (15 infants in the B.lactis Bi-07 and 15 in the placebo-treated groups) since 30 infants will provide data on the feasibility and magnitude of effect of this intervention and will inform us on sample size calculations for future studies.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
16/04/2013
Actual
Date of last participant enrolment
Anticipated
28/05/2013
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 523 0
The Royal Women's Hospital - Parkville
Recruitment postcode(s) [1] 6250 0
3052 - Parkville

Funding & Sponsors
Funding source category [1] 286648 0
Other
Name [1] 286648 0
Murdoch Childrens Research Institute & Royal Children's Hospital
Country [1] 286648 0
Australia
Funding source category [2] 286649 0
Commercial sector/Industry
Name [2] 286649 0
Danisco Sweeteners Oy,
Country [2] 286649 0
Finland
Primary sponsor type
Individual
Name
Associate Professor Mimi Tang
Address
Murdoch Childrens Research Institute & Royal Children's Hospital
50 Flemington Rd,
Parkville
VIC 3052
Country
Australia
Secondary sponsor category [1] 285431 0
Individual
Name [1] 285431 0
Associate Professor Susan Jacobs
Address [1] 285431 0
Royal Women's Hospital,
20 Flemington Rd,
Parkville,
VIC 3052
Country [1] 285431 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288723 0
RCH Human Research Ethics Committee
Ethics committee address [1] 288723 0
Ethics committee country [1] 288723 0
Australia
Date submitted for ethics approval [1] 288723 0
Approval date [1] 288723 0
Ethics approval number [1] 288723 0
31169
Ethics committee name [2] 288726 0
Research and Ethics
Ethics committee address [2] 288726 0
Ethics committee country [2] 288726 0
Australia
Date submitted for ethics approval [2] 288726 0
Approval date [2] 288726 0
Ethics approval number [2] 288726 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 37402 0
A/Prof Mimi Tang
Address 37402 0
Royal Children's Hospital,
50 Flemington Road,
Parkville,
VIC 3052
Country 37402 0
Australia
Phone 37402 0
+61 3 9345 5733
Fax 37402 0
Email 37402 0
mimi.tang@rch.org.au
Contact person for public queries
Name 37403 0
Nicole Milne
Address 37403 0
Royal Children's Hospital,
50 Flemington Road,
Parkville,
VIC 3052
Country 37403 0
Australia
Phone 37403 0
+61 3 9345 7661
Fax 37403 0
Email 37403 0
nicole.milne@rch.org.au
Contact person for scientific queries
Name 37404 0
Paul Licciardi
Address 37404 0
Royal Children's Hospital,
50 Flemington Road,
Parkville,
VIC 3052
Country 37404 0
Australia
Phone 37404 0
+61 3 9345 5554
Fax 37404 0
Email 37404 0
paul.licciardi@mcri.edu.au

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

Documents added manually
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Documents added automatically
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