Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618000095268
Ethics application status
Approved
Date submitted
19/12/2017
Date registered
22/01/2018
Date last updated
22/02/2019
Date data sharing statement initially provided
29/01/2019
Date results information initially provided
29/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A clinical trial to evaluate the influence of Casein Phosphopeptide-Amorphous Calcium Phosphate (CPP-ACP) – Cranberry toothpastes in changing the bacterial composition of dental plaque deposits on teeth of orthodontic patients.
Scientific title
Ecological approaches to dental caries prevention: A pilot controlled trial to evaluate the influence of CPP-ACP – Cranberry toothpastes in effecting an ecological change in the oral plaque microbiome on teeth of orthodontic patients.
Secondary ID [1] 293511 0
Nil Known
Universal Trial Number (UTN)
U1111-1206-3558
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Dental caries 305792 0
Condition category
Condition code
Oral and Gastrointestinal 305010 305010 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
Two test toothpastes are being trialed : (1) a CPP-ACP toothpaste with 1100 ppm fluoride, & (2) a CPP-ACP - Cranberry extract toothpaste with 1100 ppm fluoride. These two trial toothpastes will be compared with each other and with an active toothpaste that contains the standard 1100 ppm fluoride concentration, but no CPP-ACP or cranberry extract.

It is proposed that potential study participants will brush twice-daily with a pea-sized amount of one of the toothpastes as part of routine oral hygiene measures for the four weeks of the clinical trial. Which toothpaste a participant will use will be determined by a randomised blinded allocation after the study participants are recruited.

Adherence to the intervention will be monitored by weighing the toothpastes tubes at the beginning and end of the trial to estimate the extent of compliance of the study participants in using the trial toothpastes.

As with all CPP-ACP oral care products currently available in the market, the concentration of CPP-ACP in the trial toothpastes will be 10% (w/v). Highly-purified organic cranberry extracts will be added to the CPP-ACP-Cranberry toothpaste at a concentration of 250-500µg/mL.
Intervention code [1] 299805 0
Prevention
Intervention code [2] 300017 0
Treatment: Drugs
Comparator / control treatment
The details of the three trial toothpastes (2 test toothpastes and one active control toothpaste) are:

1. CPP-ACP toothpaste: this toothpaste contains 10% CPP-ACP (w/v) with 1100 ppm fluoride
2. CPP-ACP - Cranberry extract toothpaste: this toothpaste contains a highly-purified, organic polyphenol-rich cranberry extract incorporated into the CPP-ACP toothpaste also with 1100 ppm fluoride
3. Active control toothpaste: this toothpaste contains the same ingredients/vehicle and fluoride concentration (1100 ppm F) except for the CPP-ACP or cranberry.

The trial participants were instructed to brush twice daily using a pea-sized amount of their allocated toothpastes for the 5-6 weeks of the trial.
Control group
Active

Outcomes
Primary outcome [1] 304176 0
The study assessed whether the test toothpastes could effect a beneficial change in the bacterial load numbers of 14 key bacterial species (8 cariogenic and 6 health-associated bacterial species) in the dental plaque of trial participants over the 5-6 week trial period.

Molecular microbiological analysis of dental plaque samples will be done using real-time quantitative polymerase chain reaction (qPCR) by 16S rRNA sequencing of the relevant plaque bacteria.

It is hypothesized that using the test toothpastes will result in reduced bacterial loads of 'harmful' cariogenic bacteria and increased bacterial loads of 'healthy' commensal bacteria.
Timepoint [1] 304176 0
5-6 weeks after baseline appointment
Secondary outcome [1] 367267 0
None
Timepoint [1] 367267 0
Nil

Eligibility
Key inclusion criteria
(1)Undergoing fixed orthodontic treatment in both arches, with treatment having been underway for at least 1 month, (2) A minimum of 10 years of age and at least 4 fully erupted permanent maxillary anterior teeth. (3) Good general physical health as determined by a review of the medical history, (4) Available to attend a review appointment in 4 weeks, and (5) Not currently using antibiotics or any antibacterial/anti-plaque mouth rinses.
Minimum age
10 Years
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
(1) Any medical condition or disability preventing normal manual tooth brushing, (2) Allergy to milk casein proteins or intolerance to any of the components of the CPP-ACP toothpastes, (3) Unwillingness to use a fluoridated dentifrice, (4) Untreated periodontal disease, (5) Clinical evidence of active caries.

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 computers
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised sequence generation
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
For answering the hypothesis of this Phase 0/Pilot trial, the G-POWER program calculated the total sample size to be 66 (N = 22 for each of the three trial groups), based on an alpha of 0.05, power of 80% and large effect size (f = 0.4). To ensure there was sufficient statistical power in case some of the aforementioned assumptions were not met, and to account for attrition (from drop-outs or poor compliance), 30 subjects were recruited into each of the three trial groups.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/06/2018
Actual
2/07/2018
Date of last participant enrolment
Anticipated
31/08/2018
Actual
9/10/2018
Date of last data collection
Anticipated
30/09/2018
Actual
20/11/2018
Sample size
Target
90
Accrual to date
Final
90
Recruitment in Australia
Recruitment state(s)
QLD

Funding & Sponsors
Funding source category [1] 298128 0
University
Name [1] 298128 0
The University of Queensland
Country [1] 298128 0
Australia
Primary sponsor type
Individual
Name
Prof. Laurence Walsh
Address
Room Number 6410/11, Level 6, UQ School of Dentistry, 288 Herston Road, Brisbane, Queensland, Australia 4006
Country
Australia
Secondary sponsor category [1] 297272 0
None
Name [1] 297272 0
Address [1] 297272 0
Country [1] 297272 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299190 0
The Prince Charles Hospital HREC
Ethics committee address [1] 299190 0
Research Ethics and Governance Unit
The Prince Charles Hospital
Building 14
Rode Road
Chermside, Qld, 4032
Ethics committee country [1] 299190 0
Australia
Date submitted for ethics approval [1] 299190 0
10/01/2018
Approval date [1] 299190 0
14/02/2018
Ethics approval number [1] 299190 0

Summary
Brief summary
This research project aims to evaluate whether the microbial ecology of dental plaque biofilms can be altered by toothpastes containing Casein Phosphopetide-Amorphous Calcium Phosphate (CPP-ACP). Two CPP-ACP toothpastes will be assessed in this study: (1) a CPP-ACP toothpaste (commercial name MI Paste® ONE) containing 1100 ppm fluoride; and (2) an 'All-in-one' CPP-ACP toothpaste that contains natural organic cranberry extracts in addition to the CPP-ACP and 1100 ppm fluoride.
A double-blinded clinical trial will be used to compare the two CPP-ACP toothpastes with each other and with a active control toothpaste containing the standard 1100 ppm fluoride, but no CPP-ACP or cranberry extract.
Oral plaque swab samples will be collected at baseline and at end of four week trial period from study participants. The plaque samples will undergo microbial analysis to evaluate whether there any changes in the numbers of disease-causing or health-associated oral microflora, before and after using the trial toothpastes.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 2461 2461 0 0
/AnzctrAttachments/374099-Protocol.pdf (Protocol)
Attachments [2] 2462 2462 0 0
/AnzctrAttachments/374099-HREC 18-7 Final approval single site 14.02.18.pdf (Ethics approval)
Attachments [3] 2463 2463 0 0
/AnzctrAttachments/374099-PICF-adult Version1.1.pdf (Participant information/consent)
Attachments [4] 2464 2464 0 0
/AnzctrAttachments/374099-PICF-child Version 1.1.pdf (Ethics approval)
Attachments [5] 2465 2465 0 0
/AnzctrAttachments/374099-TGA CTN-05069-1'.pdf (Supplementary information)

Contacts
Principal investigator
Name 79454 0
Prof Laurence Walsh
Address 79454 0
The University of Queensland, Oral Health Centre
288 Herston Road
Herston QLD 4006
Country 79454 0
Australia
Phone 79454 0
+61 7 3365 8183
Fax 79454 0
+61 7 3365 8199
Email 79454 0
[email protected]
Contact person for public queries
Name 79455 0
Mr Nebu Philip
Address 79455 0
Room Number 6410/11, Level 6, UQ School of Dentistry, 288 Herston Road, Brisbane, Queensland, Australia 4006
Country 79455 0
Australia
Phone 79455 0
+61 452355711
Fax 79455 0
+61 7 3365 8199
Email 79455 0
[email protected]
Contact person for scientific queries
Name 79456 0
Mr Nebu Philip
Address 79456 0
Room Number 6410/11, Level 6, UQ School of Dentistry, 288 Herston Road, Brisbane, Queensland, Australia 4006
Country 79456 0
Australia
Phone 79456 0
+61 452355711
Fax 79456 0
+61 7 3365 8199
Email 79456 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
All the participant data was collected in a de-identified form.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
1171Study protocol    374099-(Uploaded-28-01-2019-11-39-49)-Study-related document.pdf
1174Ethical approval    374099-(Uploaded-28-01-2019-11-40-26)-Study-related document.pdf
1175Informed consent form    374099-(Uploaded-28-01-2019-11-42-33)-Study-related document.pdf



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
ThesisNo
Basic resultsNo 374099-(Uploaded-28-01-2019-11-37-12)-Basic results summary.docx

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseRandomized Controlled Study to Evaluate Microbial Ecological Effects of CPP-ACP and Cranberry on Dental Plaque.2020https://dx.doi.org/10.1177/2380084419859871
N.B. These documents automatically identified may not have been verified by the study sponsor.