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Trial registered on ANZCTR


Registration number
ACTRN12617000710325
Ethics application status
Approved
Date submitted
10/05/2017
Date registered
17/05/2017
Date last updated
24/04/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Randomised clinical trial of the probiotic BLIS M18 (Streptococcus salivarius) on the post-radiotherapy oral microbiome and periodontal health
Scientific title
Randomised clinical trial of the probiotic BLIS M18 (Streptococcus salivarius) on the post-radiotherapy oral microbiome and periodontal health in adults with a history of head and neck cancer
Secondary ID [1] 291907 0
None
Universal Trial Number (UTN)
U1111-1183-1833
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Head and neck cancer 303241 0
Condition category
Condition code
Oral and Gastrointestinal 302652 302652 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Cancer 302665 302665 0 0
Head and neck

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
BLIS M18 (BLIS Technologies, Dunedin, New Zealand), a lozenge containing 2.5 X 10^9 cfu per lozenge (at the time of manufacture) of the bacterial oral probiotic Streptococcus salivarius.
One lozenge daily for one month.
Patients will be asked to return any unused lozenges when they attend the final appointment.
Intervention code [1] 298031 0
Treatment: Other
Intervention code [2] 298070 0
Prevention
Comparator / control treatment
Placebo controlled study.
BLIS M18 lozenge ingredients: Isomalt, Tableting Aids, Streptococcus salivarius M18 (contains at least 2.50 billion cfu/ dose at the date of manufacture), Strawberry Flavour.
Placebo: as per BLIS M18 lozenge; Streptococcus salivarius M18 excluded
Control group
Placebo

Outcomes
Primary outcome [1] 302059 0
Microbiological changes: Real-time PCR will be performed with species-specific primers to calculate changes in the abundance of S. mutans over time and, in a composite manner, the ratio of S. mutans to S. salivarius over time.
Timepoint [1] 302059 0
Pre-intervention, four weeks post BLIS intervention commencement.
Primary outcome [2] 302112 0
Microbiological changes: Changes in the diversity of oral bacterial communities based on Illumina sequencing of the 16S rRNA gene
Timepoint [2] 302112 0
Pre-intervention, four weeks post BLIS intervention commencement.
Secondary outcome [1] 334648 0
Periodontal health: will be assessed using a periodontal probe to determine Community Periodontal Index of Treatment Need (CPITN) scores
Timepoint [1] 334648 0
Pre-intervention, four weeks post BLIS intervention commencement.
Secondary outcome [2] 334831 0
Periodontal health: Silness-Loe Plaque Index scores
Timepoint [2] 334831 0
Pre-intervention, four weeks post BLIS intervention commencement.
Secondary outcome [3] 334910 0
Microbiological changes: Changes in the predicted function of oral bacterial communities based on Illumina sequencing of the 16S rRNA gene
Timepoint [3] 334910 0
Pre-intervention, four weeks post BLIS intervention commencement.

Eligibility
Key inclusion criteria
Dentate (at least 50% of own teeth present), received radiotherapy to the head and neck region (at least 60 Gy) completed or to be completed within 7 days
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Edentulous, palliative care

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)
Lettered containers. Allocation will be recorded.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Block randomisation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving 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)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
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 outside Australia
Country [1] 8893 0
New Zealand
State/province [1] 8893 0
Auckland

Funding & Sponsors
Funding source category [1] 296414 0
University
Name [1] 296414 0
The University of Auckland
Address [1] 296414 0
The University of Auckland
Private Bag 92019
Auckland 1142
Country [1] 296414 0
New Zealand
Primary sponsor type
University
Name
The University of Auckland
Address
The University of Auckland
Private Bag 92019
Auckland 1142
Country
New Zealand
Secondary sponsor category [1] 295357 0
None
Name [1] 295357 0
Address [1] 295357 0
Country [1] 295357 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297638 0
Health and Disability Ethics Committees
Ethics committee address [1] 297638 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 297638 0
New Zealand
Date submitted for ethics approval [1] 297638 0
04/08/2016
Approval date [1] 297638 0
24/08/2016
Ethics approval number [1] 297638 0
16/STH/123
Ethics committee name [2] 297655 0
ADHB Research Review Committee
Ethics committee address [2] 297655 0
Auckland DHB
Research Office
Level 14, Support Building
Auckland City Hospital
Private Bag 92024
Grafton
Auckland 1023
Ethics committee country [2] 297655 0
New Zealand
Date submitted for ethics approval [2] 297655 0
09/06/2016
Approval date [2] 297655 0
10/05/2017
Ethics approval number [2] 297655 0
A+7396

Summary
Brief summary
Radiotherapy to the head and neck region permanently damages salivary glands, resulting in a decrease in salivary flow that manifests as a dry mouth. Post-radiotherapy, head and neck cancer patients suffer long-term changes to the oral environment, including a reduction in salivary flow that results in a loss of salivary buffering capacity. Ultimately, an increase in bacterial load and alteration of the bacterial community structure potentially have negative effects on the patient’s oral health.

Oral probiotics have been successfully shown to improve oral health, particularly in terms of reducing periodontal inflammation. The benefits of gut probiotics are well documented and include modulation of immune responses and metabolic effect – therefore, the potential mechanisms of oral probiotic action are hypothesised to be similar to those seen in the intestines: antagonism against pathogens and the reduction of inflammation and tissue destruction.

Hence, this pilot study proposes that the provision of Streptococcus salivarius in the form of an oral probiotic (BLIS M18) post-radiotherapy treatment may favorably alter the composition of the oral microbial community, reducing periodontal inflammation and improving oral health.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 74678 0
A/Prof Richard Douglas
Address 74678 0
Department of Surgery (University of Auckland)
12th Floor Support Building
Auckland City Hospital
Grafton
Auckland 1142
Country 74678 0
New Zealand
Phone 74678 0
+64 9 923 1658
Fax 74678 0
Email 74678 0
richard.douglas@auckland.ac.nz
Contact person for public queries
Name 74679 0
Dr Kim Gear
Address 74679 0
Oral Health Unit (Auckland District Health Board)
Green Lane Clinical Centre
214 Green Lane West
Epsom
Auckland 1051
Country 74679 0
New Zealand
Phone 74679 0
+64 9 630 9809
Fax 74679 0
Email 74679 0
KGear@adhb.govt.nz
Contact person for scientific queries
Name 74680 0
A/Prof Mike Taylor
Address 74680 0
School of Biological Sciences
University of Auckland
Private Bag 92019
Auckland 1142
Country 74680 0
New Zealand
Phone 74680 0
+64 9 923 2280
Fax 74680 0
Email 74680 0
mw.taylor@auckland.ac.nz

No data has been provided for results reporting
Summary results
Not applicable