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Trial registered on ANZCTR


Registration number
ACTRN12615001227583
Ethics application status
Approved
Date submitted
6/10/2015
Date registered
10/11/2015
Date last updated
15/05/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A controlled trial of Casein Phosphopeptide - Amorphous Calcium Phosphate (CPP-ACP) toothpaste in 6 year old children
Scientific title
A randomised double blind study to evaluate the effectiveness of a CPP-ACP toothpaste to prevent carious lesions in at-risk six year old children.
Secondary ID [1] 287334 0
Nil
Universal Trial Number (UTN)
U1111-1173-5442
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Dental caries 295974 0
Condition category
Condition code
Oral and Gastrointestinal 296255 296255 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Toothbrushing twice daily with a smear amount of CPP-ACP toothpaste for 12 months. At three monthly intervals, participants will be questioned on their product use/ adherence to the intervention and asked about their product supply needs.
Intervention code [1] 292654 0
Prevention
Comparator / control treatment
First comparator group - Product Control group - Toothbrushing twice daily with a smear of a placebo toothpaste for 12 months. The composition of the placebo toothpaste is identical to the CPP-ACP toothpaste minus the CPP-ACP ingredient.

Second comparator group- Community Control group - Toothbrushing twice daily with a smear of commercial fluoridated toothpaste
Control group
Placebo

Outcomes
Primary outcome [1] 295913 0
Total numbers of carious lesions and/ or demineralised tooth surfaces as detected through visual and radiographic dental examination
Timepoint [1] 295913 0
12 months from the recruitment (baseline) appointment
Secondary outcome [1] 316915 0
Levels of decay causing bacteria in their plaque collected at dental examination and assessed in a laboratory
Timepoint [1] 316915 0
12 months after the recruitment (baseline) appointment

Eligibility
Key inclusion criteria
One or more partially erupted/ erupted first molars
One or more DMFT/ dmft according to the WHO criteria
Minimum age
5 Years
Maximum age
7 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Children with a milk protein allergy
- Children with a benzoate sensitivity
- Children who are participating or have participated in the previous two years to other intervention studies
- Children using topical antimicrobials (except for fluoridated toothpaste)
- Children who have had systemic antibiotics use in the three months prior to baseline
- Children who reside in areas that have a non-fluoridated water supply
- Children who do not complete baseline treatment within 8 weeks
- Edentulous or children with less than 4 teeth
- Children with fixed or removable orthodontic appliances for cleft lip and palate
- Children with severe facial trauma

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)
Children attending Grade one and two at schools in the Metro South and Metro North Oral Health catchment will be recruited at standard dental examination. At recruitment participants will be randomised to either the CPP-ACP toothpaste, placebo toothpaste or the commercial fluoridated toothpaste group through central randomisation by computer. Participation group will be unknown for the CPP-ACP toothpaste and placebo toothpaste groups as this is a double-blinded group.

Participants recruited to the commercial fluoridated toothpaste group will be informed at the recruitment appointment after the allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
At the completion of the recruitment appointment, all participants will be randomised to the CPP-ACP toothpaste, placebo toothpaste or the commercial fluoridated toothpaste group by computer generated randomised allocation.

The CPP-ACP toothpaste and the placebo toothpaste will be pre-marked with a digital code. The codes will be provided to the chief supervisor of the study. Only after the statistical evaluation is completed will the decoding occur.
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 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Sample size: To be 80% certain of detecting a significantly difference at the end of the study, with an expected caries prevalence of 60% and 75% in the treatment versus either of the two control groups respectively, a sample size of 165 per group is required, according to a power analysis. This is based on using a Chi-squared test with a two-sided 5% significance level and allowing for a Fisher Exact test if numbers are small. Anticipating a dropout rate per year of 15% in the treatment and control groups, the target sample size is 195 in the CPP-ACP toothpaste group and 195 in the two control groups. Therefore there will be 3 groups of 195 participants (total 585). The groups are rounded up to 200 participants per group (600 in total) for ease of purchasing etc.

Analysis: At each timepoint, the CPP-ACP toothpaste group versus the placebo control group or the community control group will be compared using Chi-square tests for categorical variables (presence of caries, plaque and bacteria), and independent t-tests for continuous variables (mean number of caries, mean plaque score, mean bacterial load). Chi-square tests will also be used to examine the associations between caries and the presence of plaque and/or bacteria.

Mixed modelling will be used to assess the changes in caries incidence over time, and to examine the relationship between caries and the presence of plaque and/or bacteria over time.

All analyses will be carried out in IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp. Statistical significance will be set at 5%.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Participant recruitment difficulties
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] 4260 0
Queen Elizabeth II Jubilee Hospital - Coopers Plains
Recruitment hospital [2] 4261 0
Logan Hospital - Meadowbrook
Recruitment hospital [3] 4262 0
Redland Hospital - Cleveland
Recruitment hospital [4] 9176 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 17809 0
4029 - Herston

Funding & Sponsors
Funding source category [1] 291896 0
Other Collaborative groups
Name [1] 291896 0
CRC Oral Health
Address [1] 291896 0
Level 6, 720 Swanston Street Carlton Victoria 3053
Country [1] 291896 0
Australia
Funding source category [2] 297735 0
Government body
Name [2] 297735 0
Metro North Oral Health Service
Address [2] 297735 0
UQ Oral Health Centre, 288 Herston Road, Herston QLD, 4006
Country [2] 297735 0
Australia
Funding source category [3] 297736 0
Government body
Name [3] 297736 0
Metro South Oral Health Service
Address [3] 297736 0
Yeronga Oral Health Centre 150 Park Road, Yeronga QLD 4104
Country [3] 297736 0
Australia
Primary sponsor type
University
Name
The University of Queensland, School of Dentistry
Address
UQ Oral Health Centre
288 Herston Road, Herston QLD 4006
Country
Australia
Secondary sponsor category [1] 296767 0
None
Name [1] 296767 0
Address [1] 296767 0
Country [1] 296767 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293404 0
Metro South Human Research Ethics Commitee
Ethics committee address [1] 293404 0
PAH Centres for Health Research
Level 7, Translational Research Institute
37 Kent Street
Woolloongabba QLD 4102
Ethics committee country [1] 293404 0
Australia
Date submitted for ethics approval [1] 293404 0
15/10/2015
Approval date [1] 293404 0
03/08/2017
Ethics approval number [1] 293404 0
AM03
Ethics committee name [2] 293405 0
The University of Queensland Medical Research Ethics Commitee
Ethics committee address [2] 293405 0
UQ Research & Innovation
Cumbrae-Stewart Building (72)
THE UNIVERSITY OF QUEENSLAND QLD 4072
Ethics committee country [2] 293405 0
Australia
Date submitted for ethics approval [2] 293405 0
30/11/2015
Approval date [2] 293405 0
01/12/2015
Ethics approval number [2] 293405 0

Summary
Brief summary
This study aims to determine
- the effectiveness of using a CPP-ACP toothpaste in preventing dental caries in children
- the microbial changes in plaque such as the reduction in decay causing bacteria

Participants will attend routine dental examination appointments at public oral health services. In addition to standard examination a sample of plaque will be taken by swabbing selected teeth with a small brush. A questionnaire will be completed by the participant's parents regarding medical, social, toothbrushing and dietary histories. Dental radiographs will be taken at the recruitment appointment. All identified treatment will be undertaken.

At the first appointment, a participant's toothbrushing group will be randomly allocated. The allocation is either the CPP-ACP toothpaste or the placebo toothpaste (blinded groups) or commercial fluoridated toothpaste (non blinded). For the blinded groups (CPP-ACP and placebo), the toothpaste packaging will be marked with a digital code, but the content will not be known to the participants, the clinicians or the investigator. The codes will be provided to the chief supervisor of the study. Only after the statistical evaluation is completed will the decoding occur.

All the toothbrushes and toothpaste will be provided free of charge for the duration of the study. Participants are asked to brush twice daily will the allocated toothpaste. Compliance will be monitored by a phone call questionnaire at 3 and 9 months and in person at 6 and 12 month . The examination appointment will be repeated at 6 months and 12 months. Dental radiographs will be taken at 12 months.


Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 59758 0
Prof Laurence Walsh
Address 59758 0
The University of Queensland, Oral Health Centre
288 Herston Road
Herston QLD 4006
Country 59758 0
Australia
Phone 59758 0
+61 7 3365 8160
Fax 59758 0
+61 7 3365 8199
Email 59758 0
l.walsh@uq.edu.au
Contact person for public queries
Name 59759 0
Dr Kathryn Elsworthy
Address 59759 0
The University of Queensland, Oral Health Centre
288 Herston Road
Herston QLD 4006
Country 59759 0
Australia
Phone 59759 0
+61 7 3365 8183
Fax 59759 0
+61 7 3365 8199
Email 59759 0
k.elsworthy@uq.edu.au
Contact person for scientific queries
Name 59760 0
Dr Kathryn Elsworthy
Address 59760 0
The University of Queensland, Oral Health Centre
288 Herston Road
Herston QLD 4006
Country 59760 0
Australia
Phone 59760 0
+61 7 3365 8183
Fax 59760 0
+61 7 3365 8199
Email 59760 0
k.elsworthy@uq.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary