ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12615000341527

Ethics application status

Approved

Date submitted

26/03/2015

Date registered

15/04/2015

Date last updated

27/11/2019

Date data sharing statement initially provided

27/11/2019

Date results provided

27/11/2019

Type of registration

Prospectively registered

Titles & IDs

Public title

Efficacy of oral probiotics in improving oral hygiene for orthodontic patients

Scientific title

Efficacy of the oral probiotic Streptococcus salivarius in managing
biofilm formation in patients wearing fixed orthodontic appliances: A double-blind randomized placebo-controlled trial

Secondary ID [1]

Nil

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

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

caries

enamel demineralization

gingivitis

gingival inflammation

halitosis

Condition category

Condition code

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

The probiotic lozenges that have been demonstrated efficacious in primary-school-aged children and university-aged adults will be used as the treatment intervention.
These probiotic lozenges contain a probiotic strain, S. salivarius M18 (BLIS Technologies Ltd, Dunedin, New Zealand).
The protocol will require the participants to suck two lozenges each day, one after brushing the teeth in the morning and one after teeth brushing at night.
a) the dose administered: 3.6 billion S. salivarius CFUs/lozenge;
b) the duration/frequency of administration: daily for 4 weeks;
c) the mode of administration: taken by mouth;
d) strategy used to monitor adherence to the intervention: unused lozenge return.

Intervention code [1]

Prevention

Comparator / control treatment

Placebo-control, which differs only in containing additional sugar substitutes in place of the S. salivarius M18, will be used in the control group. The active and placebo preparations will be identical in appearance and taste.

Control group

Placebo

Outcomes

Primary outcome [1]

1. Plaque Index (PI): PI will be used to measure the amount of biofilm formation by using the modified Silness and Loe Plaque Index (PI) and a periodontal probe (Al-Anezi and Harradine, 2012).

Timepoint [1]

The duration of the study will be 4 months in total, including a 1-month treatment intervention followed by a 3-month treatment-free follow-up to assess recurrence rates. This means at the baseline, 1st, and 4th month, the participants’ mouths will be examined and samples will be collected for the assessments.

Primary outcome [2]

2. Proportion of ‘good’ bacteria and ‘bad’ bacteria in the dental biofilm: Samples for detecting the proportion of probiotics (S. salivarius M18), pathogenic microbes (S. mutans, A. actinomycetemcomitans, P. gingivalis), and other oral microflora in the dental biofilm will be collected from the gingival areas of the upper lateral incisors, using sterilized dental probes. The microbial profiles of biofilm will be analyzed firstly by direct PCR-based amplification of the 16S ribosomal RNA gene followed by sequencing of the PCR products using next-generation DNA sequencing (Ion Torrent) technology. The 16S rRNA gene is considered the ‘gold standard’ for bacterial identification, which is able to identify the known species and possibly identify the microorganisms that cannot be cultured.

Timepoint [2]

Primary outcome [3]

3. Levels of volatile sulphur compounds (VSCs) in mouth: Levels of VSCs will be assessed by patients’ air samples (breath scores) using a halimeter (Interscan Corp., Chatsworth, USA) based on the average of three readings.

Timepoint [3]

Secondary outcome [1]

The side effects, including bloating and flatulence, will also be assessed by asking patient's feedbacks at each monthly orthodontic visit.

No harm to the patients is anticipated, however, if any serious adverse events are observed in any of the participants, the study will be terminated immediately.

Timepoint [1]

All measurements will be taken by a blinded investigator at each monthly orthodontic visit from baseline for 4 months.

Secondary outcome [2]

Patient's compliance will also be monitored and assessed by using sticker charts. Each patient will be asked to fill in a sticker chart everyday to record the usage of tablets.

Timepoint [2]

All measurements will be taken by a blinded investigator at each monthly orthodontic visit from baseline for 4 months.

Eligibility

Key inclusion criteria

Inclusion criteria: age 10-30 years; at least 20 natural teeth (extraction and non extraction patients); wearing conventional stainless steel brackets (3M Unitek) in both arches; using a fluoride toothpaste not containing any supplementary antibacterial agents for daily oral hygiene. The patients will be willing to participate in the study and will be required to sign an informed consent form.

Minimum age

10 Years

Maximum age

30 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Exclusion criteria: systemic disease (i.e. diabetes); periodontal diseases; antibiotic therapy; dental fluorosis; smoking; use of powered toothbrushes; lactose intolerant; allergic to dairy products.

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)

Balanced block randomization will be used to ensure equal patient allocation to each treatment group.
Allocation concealment will be used to avoid selection bias.

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

The computer-generated random numbers will be provided in opaque, sealed envelopes before interventions.

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

Safety/efficacy

Statistical methods / analysis

Data will be firstly analyzed by descriptive statistics and normality tests. An intention-to-treat analysis will be carried using mixed-models and, where appropriate, nonparametric Kruskal-Wallis. The statistical software SPSS 20 and STATA 13 will be used. Alfa error will be set at 0.05.

Sample size calculation and statistical power are based on our previous RCT research (Peng Y, et al. Effect of visual method vs plaque disclosure in enhancing oral hygiene in adolescents and young adults: A single-blind randomized controlled trial. Am J Orthod Dentofacial Orthop. 2014;145:280-286). Type I error is set at 0.05 and type II error at 0.20 (80% power). At least 27 patients (i.e., a total of 54 for two groups) will be needed to detect a decrease in biofilm formation of about 30%. To account for possible dropouts during the study, we plan to recruit a total of 64 patients.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

1/05/2015

Actual

1/07/2015

Date of last participant enrolment

Anticipated

Actual

31/12/2015

Date of last data collection

Anticipated

Actual

30/06/2016

Sample size

Target

Accrual to date

Final

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Dunedin

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

The New Zealand Dental Association Research Foundation

Address [1]

NZDA House, Building 1, 195 Main Highway Ellerslie, Auckland 1051, PO Box 28084, Remuera 1541

Country [1]

New Zealand

Primary sponsor type

University

Name

Faculty of Dentistry, University of Otago

Address

310 Great King Street, Dunedin, 9016

Country

New Zealand

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

University of Otago Ethics Committee

Ethics committee address [1]

362 Leith Street, Dunedin, 9016

Ethics committee country [1]

New Zealand

Date submitted for ethics approval [1]

01/05/2014

Approval date [1]

12/08/2014

Ethics approval number [1]

Summary

Brief summary

There is an increasing demand for orthodontic treatment due to its benefits in improving smiles, self-esteem and jaw function. However, braces make it more difficult to brush teeth effectively and therefore increase the accumulation of bacterial plaque (dental biofilm) in these hard-to-brush areas. Plaque can lead to problems such as tooth demineralization, bleeding gums and bad breath. These consequences significantly affect orthodontic treatment results and a patient’s quality of life. 
The prevalence of these biofilm-related problems, such as enamel demineralization, still remain as high as 72.9% in patients wearing braces. Many dental products are commercially available to prevent plaque buildup, with little effect. These include interdental brushes, specialized orthodontic toothbrushes, antimicrobial mouth rinses and toothpastes. The need for an effective measure of biofilm control is important and it is even greater in patients wearing braces.
Probiotics are live ‘good’ bacteria that can inhibit ‘bad’ bacteria in biofilms. Regular consumption of oral probiotics has been reported as an effective way for managing plaque in preschool children, primary-school children, adolescents, adults and the elderly. However, the effect of oral probiotics on controlling biofilm in patients wearing braces has not been investigated to date.
The probiotic Streptococcus salivarius, developed at the University of Otago, is the world’s first probiotic for the mouth. It has been shown to be effective and beneficial for the prevention and treatment of biofilm-related problems such as dental decay, gum inflammation and bad breath.
We intend to investigate the effect of probiotic Streptococcus salivarius in managing the biofilm in patients wearing braces and see whether it can reduce dental biofilm accumulation, its unwanted side effects and offer patients a new beneficial oral micro-ecology.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Li Mei

Address

Department of Oral Sciences, Faculty of Dentistry, University of Otago. 310 Great King Street, Dunedin, 9016

Country

New Zealand

Phone

+64 3 479 7480

Fax

li.mei@otago.ac.nz

Contact person for public queries

Name

Gareth Benic

Address

Department of Oral Sciences, Faculty of Dentistry, University of Otago. 310 Great King Street, Dunedin, 9016

Country

New Zealand

Phone

+64 3 479 7480

Fax

gzbenic@gmail.com

Contact person for scientific queries

Name

Li Mei

Address

Department of Oral Sciences, Faculty of Dentistry, University of Otago. 310 Great King Street, Dunedin, 9016

Country

New Zealand

Phone

+64 3 479 7480

Fax

li.mei@otago.ac.nz

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
5901	Ethical approval			li.mei@otago.ac.nz

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Oral probiotics reduce halitosis in patients wearing orthodontic braces: A randomized, triple-blind, placebo-controlled trial.	2019	https://dx.doi.org/10.1088/1752-7163/ab1c81

N.B. These documents automatically identified may not have been verified by the study sponsor.

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