Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000187448
Ethics application status
Approved
Date submitted
4/02/2025
Date registered
18/02/2025
Date last updated
18/02/2025
Date data sharing statement initially provided
18/02/2025
Type of registration
Retrospectively registered

Titles & IDs
Public title
Omics of saliva, GCF and plaque in periodontitis management
Scientific title
Omics of oral biosamples in periodontitis participants compared to healthy participants
Secondary ID [1] 313870 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Periodontitis 336536 0
Condition category
Condition code
Oral and Gastrointestinal 333049 333049 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Observational
Patient registry
True
Target follow-up duration
12
Target follow-up type
Months
Description of intervention(s) / exposure
o Baseline and initial treatment visit (0-month; 1 hour duration)
o Pre-operative periodontal charting recorded by registered periodontists (Ivanovaki, Lee, and otherrelevant staff) or DClinDent postgraduate registrars, with a periodontal UNC probe. All examiners will becalibrated.
o This will allocate participants into the group categories: periodontal health, gingivitis and periodontitis (with and without systemic diseases)
o Saliva, gingival crevicular fluid (GCF) and plaque samples will be collected from all Groups,
- For saliva collection: participants will be asked to refrain from eating and drinking for at least one hourprior to saliva sample collection. At the appointment, participants will rinse their mouths with ~10 mL ofwater to remove the food debris. Unstimulated whole saliva through spitting (5mL ideally; minimum 1-1.5ml) will be collected.
- GCF will be collected prior to commencing treatment to avoid contamination via blood. This willbe conducted using our established
protocol (Han et al, 2023, PMID: 35771077) where paper strips (Oraflow)will be inserted into the deepest site of each quadrant (to
reduce saliva contamination) and pooled.
- For healthy patients: 6 paper strips will be collected each from 6 healthy sites (free of inflammation and BOP) from the same
tooth and pooled. Up to 3 teeth will be collected
- For gingivitis patients: 6 paper strips will be collected from 6 inflamed sites (or 2 sites from the same tooth)
- For periodontitis patients: up to 6 paper strips will be collected each from 1 deepest site and 1 healthy site
o Plaque, GCF and saliva samples will be placed in sterile glycerol (final concentrations: 15-30%), or stored immediately at -80 degrees at the Research Lab, Level 6, Oral Health Centre, until elution andextraction. Extracellular vesicles from those samples may be isolated and compared the omics between orginal oral samples and their derived EVs. Samples containing glycerol may be subjected to in vitro culturing for biofilm development prior to bacterial extracellular vesicles omics (proteome, methylome, microbiome, lipidome and metabolome or relevant omes), with saliva, GCF and plaque samples used as controls.

Patients in the periodontitis group will be allocated the next available appointment for standard care,receiving supragingival and subgingival non-surgical debridement using hand scalers and ultrasonicinstruments over 2 appointments (60-90 mins duration per appointment). Routine surgical treatment may be performed if deemed necessary.
Follow-up reviews (3-, 6-, 12- and 18-mo post-periodontal treatment; 1-1.5 hours duration)
o Periodontitis patients will be recalled 3 mo following debridement to re-assessperiodontal parameters and recollect saliva and GCF (from the same sites as baseline appointment).
o They will then receive the standard protocol of care, including oral hygiene instruction (OHI), non-surgicalre-instrumentation of persistent sites and supragingival maintenance of remaining sites.
o Patients will then be recalled at the 3, 6 12, and 18 mo time points (since initial therapy)
o Patient compliance with treatment reviews will be recorded using a clinic attendance checklist.
Salivary omics (proteome, lipidome, metabolome), GCF cytokines and plaque bacterial load and omics (16S sequencing, metagenomic sequencing, and ITS sequencing) will be conducted for all samples.
Intervention code [1] 330460 0
Diagnosis / Prognosis
Intervention code [2] 330459 0
Early Detection / Screening
Comparator / control treatment
Individuals in the periodontally healthy groups will serve as healthy controls, as they are already in a healthy condition and do not require additional treatment. All these patients do not have self-reported systematic diseases. Periodontally healthy patients are healthy patients who do not have any periodontal disease but were treated by dentists at the same clinic (for dental conditions other than a periodontal disease).

Unstimulated saliva, GCF and plaque samples (from molars) will be collected from these healthy controls
GCF samples from periodontally healthy patients: up to 6 paper strips will be collected each from up to 6 healthy sites (free of inflammation and BOP) from the same tooth and pooled,
Control group
Active

Outcomes
Primary outcome [1] 340598 0
Change in probing pocket depth (PPD)
Timepoint [1] 340598 0
Baseline, 3-, 6-, 12- and 18-month post routine periodontal treatment
Secondary outcome [1] 444552 0
Salivary omics profiles in all collected saliva samples
Timepoint [1] 444552 0
Baseline, 3-, 6-, 12- and 18-month post routine periodontal treatment
Secondary outcome [2] 444553 0
Plaque microbiome in all collected dental plaque samples
Timepoint [2] 444553 0
Baseline, 3-, 6-, 12- and 18-month post routine periodontal treatment
Secondary outcome [3] 444554 0
GCF cytokine profiles
Timepoint [3] 444554 0
Baseline, 3-, 6-, 12- and 18-month post routine periodontal treatment

Eligibility
Key inclusion criteria
Patients 18 years of age or older.
For the periodontal health group (n=30):
BOP<=10% and PPD<=3mm

For the periodontitis group* (n=40):
Stage III-IV periodontitis patients will have interdental CAL=5mm, PPD=6mm, and significant radiographicbone loss.
*Based on Chapple et al 2018
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Uncontrolled diabetes (HbA1c>11%)
periodontal treatment or antibiotics therapy three months prior to investigation
pregnancy, smokers, active infectious disease

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Convenience sample
Timing
Both
Statistical methods / analysis
For descriptive analysis of categorical data, absolute and relative frequencies will be calculated. Thenumerical data will be first assessed for approximate normality. Chi-square tests and one-way ANOVA willbe used for inferential analysis comparing the demographic data and outcome characteristics at baseline.Data will be displayed in a table form.
• To take into account correlations within subjects, random-intercept linear regression models will be applied to evaluate salivary omics, plaque microbiomes and GCF cytokines changes over time in periodontal study groups (healthy, periodontitis). This will be displayed in the form of a line graph showing trends over time.
• The significance of differences (expression level of differentially expressed protein, lipids, metabolites, micribia, EVs and EV content) between periodontal study groups (healthy, periodontitis) at each time-point will be assessed using one-way ANOVA and Kruskal-Walls tests.
• The significance of differences within pairs of groups over certain time points will be assessed usingpaired Friedman test followed by post-tests.
• Confidence interval 95% with p value < 0.05.
• Multi-variate analyses using will be conducted to adjust for confounders (smoking, plaque control, age,sex, ethnicity) and subanalysis of different staging of periodontitis.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
4/02/2025
Date of last participant enrolment
Anticipated
25/02/2027
Actual
Date of last data collection
Anticipated
23/02/2029
Actual
Sample size
Target
150
Accrual to date
25
Final
Recruitment in Australia
Recruitment state(s)
QLD

Funding & Sponsors
Funding source category [1] 318336 0
University
Name [1] 318336 0
School of Dentistry - University of Queensland
Country [1] 318336 0
Australia
Primary sponsor type
University
Name
School of Dentistry - University of Queensland
Address
Country
Australia
Secondary sponsor category [1] 320731 0
University
Name [1] 320731 0
School of Dentistry - University of Queensland
Address [1] 320731 0
Country [1] 320731 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316972 0
Metro North Health Human Research Ethics Committee B
Ethics committee address [1] 316972 0
Ethics committee country [1] 316972 0
Australia
Date submitted for ethics approval [1] 316972 0
15/07/2020
Approval date [1] 316972 0
17/03/2021
Ethics approval number [1] 316972 0
54584
Ethics committee name [2] 316977 0
The University of Queensland Human Research Ethics Committee A
Ethics committee address [2] 316977 0
Ethics committee country [2] 316977 0
Australia
Date submitted for ethics approval [2] 316977 0
24/03/2021
Approval date [2] 316977 0
13/04/2021
Ethics approval number [2] 316977 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 139614 0
Dr Pingping Han
Address 139614 0
The University of Queensland, School of Dentistry, 288 Herston Road, Herston, 4006, QLD
Country 139614 0
Australia
Phone 139614 0
+61 07 33658172
Fax 139614 0
Email 139614 0
[email protected]
Contact person for public queries
Name 139615 0
Pingping Han
Address 139615 0
The University of Queensland, School of Dentistry, 288 Herston Road, Herston, 4006, QLD
Country 139615 0
Australia
Phone 139615 0
+61 07 33658172
Fax 139615 0
Email 139615 0
[email protected]
Contact person for scientific queries
Name 139616 0
Prof Saso Ivanovski
Address 139616 0
The University of Queensland, School of Dentistry, 288 Herston Road, Herston, 4006, QLD
Country 139616 0
Australia
Phone 139616 0
+61 07 336 58064
Fax 139616 0
Email 139616 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


What supporting documents are/will be available?

No Supporting Document Provided


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.