ANZCTR - Registration

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

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Trial registered on ANZCTR

Registration number

ACTRN12618000265279p

Ethics application status

Not yet submitted

Date submitted

14/02/2018

Date registered

21/02/2018

Date last updated

21/02/2018

Type of registration

Prospectively registered

Titles & IDs

Public title

Restoring gut health of newborns- a clinical trial of probiotics

Scientific title

Restoring neonatal gut biodiversity and mucosal immunity after postnatal antibiotics exposure (Restore trial)

Secondary ID [1]

None

Universal Trial Number (UTN)

U1111-1204-2229

Trial acronym

RESTORE

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Neonatal gut microbial biodiversity

Immune development

Condition category

Condition code

Reproductive Health and Childbirth

Complications of newborn

Oral and Gastrointestinal

Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

multi-strain probiotic powder (multiple strains of lactobacilli and bifidobacterium, 7 billion cfu per gram- supplied in 3x60gm bottles) - two grams (two scoops) dissolved in expressed breast milk every day for 12 weeks orally
Adherence/compliance to intervention will be monitored by parental diary and by measuring left over powder on return of bottles at the end of intervention

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

similar looking powder of placebo containing maltodextrin (supplied in 3x60gm bottles) - two grams (two scoops) every day for 12 weeks orally
The reference group (40 infants of matched gestation without antibiotic exposure) will not receive any treatment.

Control group

Placebo

Outcomes

Primary outcome [1]

Stool microbial diversity - by 16S rRNA sequencing

Timepoint [1]

4 weeks of age

Secondary outcome [1]

stool microbial diversity - by 16S rRNA sequencing
This analysis will show whether the effect of probiotics on diversity is sustained beyond post-cessation.

Timepoint [1]

12 weeks of age (at treatment completion), 6 months of age (3 months post-treatment completion) and 12 months of age (9 months post-treatment completion)

Secondary outcome [2]

Secretory IgA stool

Timepoint [2]

4 weeks of age (4 weeks post-treatment commencement), 12 weeks of age (at treatment completion), 6 months of age (3 months post-treatment completion) and 12 months of age (9 months post-treatment completion)

Secondary outcome [3]

medically diagnosed allergy/eczema/atopy - assessed by parents questionnaire designed for this study

Timepoint [3]

12 months of age (9 months post-treatment completion)

Secondary outcome [4]

Secretory IgA in saliva

Timepoint [4]

Eligibility

Key inclusion criteria

Newborns (gestation > or equal to 37+0 weeks) who have been given antibiotics for clinical indications (at least two doses) within 48 hours of birth
Age and gestation matched newborns without antibiotic exposure will be included as the 'reference group'

Minimum age

0 Days

Maximum age

3 Days

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

-gestational age <37 weeks
-anticipated exposure of antibiotics more than 5 days post birth
-major congenital anomalies (e.g. gastroschisis)
-bilious vomiting
-probiotic intake other than study drug by mum or baby

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)

Centrally computer-generated randomisation will be used and the trial pharmacist (unblinded) will allocate participants to probiotic or placebo group. Participants, clinicians and the investigators will be blinded to the group allocation.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

block randomization

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

40 probiotic group, 40 placebo and 40 babies not exposed to antibiotics used as reference group

Phase

Not Applicable

Type of endpoint/s

Efficacy

Statistical methods / analysis

Intention to treat analysis

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

1/11/2018

Actual

Date of last participant enrolment

Anticipated

30/06/2019

Actual

Date of last data collection

Anticipated

30/06/2020

Actual

Sample size

Target

120

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Recruitment hospital [1]

Fiona Stanley Hospital - Murdoch

Recruitment postcode(s) [1]

6150 - Murdoch

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Fiona Stanley Hospital

Address [1]

11 Robin warren drive, Murdoch WA 6150

Country [1]

Australia

Primary sponsor type

Hospital

Name

Fiona Stanley Hospital

Address

11 Robin warren drive, Murdoch WA 6150

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Not yet submitted

Ethics committee name [1]

South Metro Area Health Service Ethics Committee

Ethics committee address [1]

Fiona Stanley Hospital, Education Building, 11 Robin Warren Drive, Murdoch WA 6150

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

30/05/2018

Approval date [1]

Ethics approval number [1]

Summary

Brief summary

Due to high susceptibility to infections, antibiotics are the most widely used drugs for newborns. Recent evidence suggests that antibiotics exposure in newborn period (first 4 weeks of life) predisposes to an imbalance in the gut, which may have long lasting consequences. Imbalances in the infants’ gut bacteria (microbiome) caused by antibiotics has been shown to alter the development of the neonate’s immune response. This altered immune development caused by a poorly balanced microbiome during this crucial phase of early life has been associated with the development of atopy, asthma, eczema, allergy, type 1 diabetes and inflammatory bowel disease. Mucosal immunity development in the gut has been shown to be aberrant as early as one month of age in children who go on to develop allergy symptoms in future. RESTORE is a clinical trial of a multi-strain probiotic for antibiotics exposed term newborn infants with aims to restore biodiversity and reduce dysbiosis (imbalance of bacteria) in the newborn gut in early months after birth. This is the first study of its kind to examine effects of probiotics on these high-risk infants’ gut biodiversity and mucosal immune development.
Research Questions 
1.	Can the gut microbial diversity of infants exposed to postnatal antibiotics be restored earlier (within neonatal period after birth) by daily use of multi-strain probiotic supplementation?
2.	Is this effect sustained at 3 months and 12 months?
3.	Can probiotics in antibiotic exposed infants improve the production of salivary and secretory IgA to that seen in infants without antibiotics exposure?
Methodology
This randomised control trial will be conducted at Fiona Stanley Hospital. A total of 120 term neonates will be recruited, 80 of whom would have received antibiotics at birth for clinical reasons. Forty of the antibiotic exposed neonates will receive daily probiotics for 3 months and forty infants will receive a placebo. Forty infants without antibiotic exposure will serve as a reference group. Stool, saliva and blood will collected for microbiome and/or immunological tests at five time-points in the first 12 months of life. 
Predicted Benefits and Relevance: 
Neonatal infections, antibiotic use and allergy in later life are highly relevant health issues for infants, with gut microbiome as the potential denominator. In Australia, the economic cost of allergic diseases is estimated to be >$30 billion annually. Probiotics have been extensively used to restore microbiome balance in adults and hold potential to be useful for newborns for this indication. Although some promising data exists from animal studies, No human studies have yet determined whether probiotics are effective in rapidly restoring the balance of bacteria in term neonates’ gut following exposure to antibiotics. We are proposing a randomised control trial to determine if multi-strain probiotics can rapidly normalize the infants’ microbiome following neonatal antibiotic exposure during the crucial time of immune development and improve mucosal immunity. This study will provide insights for conducting larger multicentre trial to confirm clinical benefits; which will potentially change the practice to routinely supplement these high-risk babies with probiotics in the newborn period.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Shailender Mehta

Address

Fiona Stanley Hospital, 11 Robin Warren Drive, Murdoch WA 6150

Country

Australia

Phone

+61861522222

Fax

shailender.mehta@health.wa.gov.au

Contact person for public queries

Name

Shailender Mehta

Address

Fiona Stanley Hospital, 11 Robin Warren Drive, Murdoch WA 6150

Country

Australia

Phone

+61861522222

Fax

shailender.mehta@health.wa.gov.au

Contact person for scientific queries

Name

Shailender Mehta

Address

Fiona Stanley Hospital, 11 Robin Warren Drive, Murdoch WA 6150

Country

Australia

Phone

+61861522222

Fax

shailender.mehta@health.wa.gov.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

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No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

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