Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000458134
Ethics application status
Approved
Date submitted
13/03/2019
Date registered
20/03/2019
Date last updated
19/05/2022
Date data sharing statement initially provided
20/03/2019
Date results information initially provided
16/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Water Quality and the Microbiome Study - TUMS
Scientific title
The impact of chlorinated drinking water on the assembly of the infant gut microbiome
Secondary ID [1] 297673 0
None
Universal Trial Number (UTN)
U1111-1229-7839
Trial acronym
TUMS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Intestinal microbiome 312030 0
atopic disease 312031 0
Condition category
Condition code
Oral and Gastrointestinal 310533 310533 0 0
Normal oral and gastrointestinal development and function
Inflammatory and Immune System 310599 310599 0 0
Allergies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be randomised into two groups to experience the following drinking water regimes for a period of up to 12 months: [1] Unmodified tap water as distributed by the local public water supply (n=100) (‘control’ group); and [2] Filtered tap water by means of activated carbon ion exchange to remove dissolved chlorine and other contaminants (n=100) (‘treatment’ group). Participants will be instructed to maintain normal practises around water consumption throughout the intervention period.

A benchtop water filtration unit fitted with a 0.5-micron carbon cartridge will be installed in participants’ homes. The filter has an output of 5,000 liters and should not require replacement within the 12-month period of intervention. The carbon block interior effectively removes chloramines, chlorine, pesticides and heavy metals, but does not remove fluoride so poses no risk to dental health. Sham filters will look identical but contain a sediment filter that only removes large sediment particles.

Multipure Drinking Water Systems filter and housing units will be installed in participants' homes as the primary source of drinking water for infants. Multipure Drinking Water Systems filter and housing units are tested according to NSF/ANSI Standard 42 (Aesthetic Effects) and Standard 53 (Health Effects) [certification #C0303273]. Multipure drinking water systems are designed to be used where the water is microbiologically safe and has been adequately disinfected. The intervention group will receive housing units containing the Hi-Tech Optimizer carbon filtration blocks that are rated to reduce >97% of chloramines and >99% of chlorine, but do not remove fluoride. The control group will receive identical housing units that contain a sediment only filter that does not alter the chemical composition of tap water.

To maintain the blind, the filtration units look identical and will be distributed to the TUMS team to install in participant homes by the independent randomisation party without notifying of the internal filter unit. Parents who wish to participate will be randomised to the treatment or control arm of the study and an appointment will be made for our investigator to visit their home for an initial recruitment visit. At the recruitment visit, the investigator will give an overview of the study, answer any questions and record consent into the study. The investigator will fit the benchtop water filter to the kitchen tap.

The intervention will start from study entry at 6 months of age and continue until 18 months of age. We have chosen our intervention period to reflect current NHMRC infant feeding guidelines which recommend introducing boiled tap water (which removes chlorine) from 6 months, and unboiled tap water from 12 months. Therefore, our baseline sample of the microbiome at 6 months reflects a time-point where we expect little to no chlorine exposure, and our community survey of origins participants suggests this to be the case.

The intervention period lasts for 12-months which represents a pragmatic study design as the filter cartridges are rated for 12-months or 5,000 litres.
Intervention code [1] 313910 0
Prevention
Comparator / control treatment
The control group will receive identical housing units that contain a sediment only filter that does not alter the chemical composition of tap water. Sham filters will look identical to the intervention filters, but contain a sediment filter that only removes large sediment particles.
Control group
Placebo

Outcomes
Primary outcome [1] 319393 0
The primary outcome will be change in the microbiome measured on fecal samples
Timepoint [1] 319393 0
6 months, 12 months and 18 months [primary timepoint] of age.
Secondary outcome [1] 368006 0
We will also examine for other allergic disease manifestations during infancy and early childhood:
• Sensitisation to foods (egg, milk and peanut) and inhalant allergens (cat, dog, cockroach, grass mix, house dust mite), assessed by skin prick test,
Timepoint [1] 368006 0
at 1 and 2.5 years of age
Secondary outcome [2] 368007 0
We will also examine for other allergic disease manifestations during infancy and early childhood :
• IgE-mediated food allergies to egg, milk or peanut, determined through participant reporting in study-specific questionnaires.
Timepoint [2] 368007 0
at 1 and 2.5 years of age
Secondary outcome [3] 368008 0
We will also examine for other allergic disease manifestations during infancy and early childhood:
• Subsequent eczema determined through SCORAD assessment and study-specific questionnaire.
Timepoint [3] 368008 0
at 1 and 2.5 years of age
Secondary outcome [4] 368009 0
We will also examine for other allergic disease manifestations during infancy and early childhood:
• Recurrent wheeze determined from study specific questionnaires
Timepoint [4] 368009 0
at 1 and 2.5 years of age
Secondary outcome [5] 368010 0
We will also monitor infant and early childhood growth anthropometry measures of height (cm), weight (kg), BMI (kg/m2) and head circumference (cm) measured with height gauges and scales.
Timepoint [5] 368010 0
at 12 months and 2.5 years
Secondary outcome [6] 368011 0
constipation recorded from study specific questionnaires
Timepoint [6] 368011 0
12-months and 2.5 years
Secondary outcome [7] 368361 0
Hospitalisations from study specific questionnairs
Timepoint [7] 368361 0
12-months and 2.5 years

Eligibility
Key inclusion criteria
Infants of age 6 months who meet the following criteria:
• Born term
• Without congenital birth defects
• Are intending on remaining in the Perth metropolitan area for the next two years to the best of their knowledge
• Speak English as the primary language at home
Minimum age
6 Months
Maximum age
12 Months
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• Enrolled in another dietary intervention study
• Has received any antibiotics since birth
• Home is not connected to public water supply
• Currently using or intend to use a water filtration system or bottled water to prepare drinks for their infants within the next two years.

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)
Central randomisation by computer administered by an independent team
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation by computer software
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
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
1/08/2019
Actual
4/11/2019
Date of last participant enrolment
Anticipated
3/05/2021
Actual
30/03/2021
Date of last data collection
Anticipated
3/05/2023
Actual
30/04/2022
Sample size
Target
200
Accrual to date
Final
197
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 13407 0
Joondalup Health Campus - Joondalup
Recruitment postcode(s) [1] 26009 0
6027 - Joondalup

Funding & Sponsors
Funding source category [1] 302201 0
Charities/Societies/Foundations
Name [1] 302201 0
Telethon Kids Institute Bluesky Award
Country [1] 302201 0
Australia
Primary sponsor type
Individual
Name
Telethon Kids Institute
Address
Telethon Kids Institute,
Northern entrance,
Perth Children's Hospital
15 Hospital Avenue
Nedlands,
WA 6009
Country
Australia
Secondary sponsor category [1] 302044 0
Hospital
Name [1] 302044 0
Joondalup Health Campus
Address [1] 302044 0
Cnr Grand Blvd & Shenton Ave
JOONDALUP WA 6027
Country [1] 302044 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302880 0
Ramsay Health Care WA | SA HREC (EC00266)
Ethics committee address [1] 302880 0
Level 8, 154 Pacific Highway, St Leonards, NSW 2065
Ethics committee country [1] 302880 0
Australia
Date submitted for ethics approval [1] 302880 0
20/03/2019
Approval date [1] 302880 0
14/06/2019
Ethics approval number [1] 302880 0
1911
Ethics committee name [2] 308766 0
University of Western Australia
Ethics committee address [2] 308766 0
35 Stirling Highway, Crawley, Perth WA 6009
Ethics committee country [2] 308766 0
Australia
Date submitted for ethics approval [2] 308766 0
Approval date [2] 308766 0
18/05/2020
Ethics approval number [2] 308766 0
RA/4/20/6106

Summary
Brief summary
This project examines whether tap water effects the natural spatial and temporal organisation of the gut microbial communities (the microbiome) during infancy and early childhood.



The addition of chlorine to metropolitan drinking water is one of the most effective means to deliver safe drinkable water because it produces a residual disinfectant that persists within the water distribution system. Levels of chlorine used to treat metropolitan water are considered safe for the individual based on toxicity studies. However, to our knowledge there have been no studies examining whether persistent chlorine exposure from tap water is also safe for the friendly gut bacteria that colonise the gastrointestinal tract. Chlorine has potent anti-microbial properties, and potentially forms disinfection by-products that can disrupt the intestinal microbiome in early childhood. Persistent exposure to low levels of chlorine may potentially cause an imbalance in the types of organisms present in the gut and may contribute to a range of health conditions.



The present study is a randomized controlled trial (RCT) comparing the gut microbial colonisation patterns in early life. The RCT will enroll 220 healthy infants at six months of age, who will be randomised into two groups to experience the following drinking water regimes: 1) unmodified tap water as distributed by the local public water supply (‘control’ group); and 2) filtered tap water with chlorine and other contaminants removed (‘treatment’ group). Infants will be followed up through to 18 months of age. The primary outcome will be changes in the gut microbiome at 6 months, 12 months and 18 months of age. The secondary outcomes will be infant clinical health outcomes at 12 months and 2.5 years of age.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 91714 0
Dr David Marrtino
Address 91714 0
Telethon Kids Institute,
Northern Entrance, Perth Children's Hospital.
15 Hospital Avenue, Nedlands,
Perth, WA 6009.
Country 91714 0
Australia
Phone 91714 0
+61 08 63191635
Fax 91714 0
Email 91714 0
david.martino@telethonkids.org.au
Contact person for public queries
Name 91715 0
Dr David Marrtino
Address 91715 0
Telethon Kids Institute,
Northern Entrance, Perth Children's Hospital.
15 Hospital Avenue, Nedlands,
Perth, WA 6009.
Country 91715 0
Australia
Phone 91715 0
+61 08 63191635
Fax 91715 0
Email 91715 0
david.martino@telethonkids.org.au
Contact person for scientific queries
Name 91716 0
Dr David Marrtino
Address 91716 0
Telethon Kids Institute,
Northern Entrance, Perth Children's Hospital.
15 Hospital Avenue, Nedlands,
Perth, WA 6009.
Country 91716 0
Australia
Phone 91716 0
+61 08 63191635
Fax 91716 0
Email 91716 0
david.martino@telethonkids.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
12087Study protocol    377164-(Uploaded-21-05-2020-23-27-43)-Study-related document.docx
12088Informed consent form    377164-(Uploaded-21-05-2020-23-29-15)-Study-related document.docx
12089Ethical approval    377164-(Uploaded-21-05-2020-23-31-03)-Study-related document.pdf



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.