Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000392460
Ethics application status
Approved
Date submitted
7/04/2025
Date registered
1/05/2025
Date last updated
1/05/2025
Date data sharing statement initially provided
1/05/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Host and microbial derived extracellular vesicles in oral biofluids in periodontitis patients with and without Type 2 Diabetes Mellitus.
Scientific title
Host and microbial derived extracellular vesicles in oral biofluids in periodontitis patients with and without Type 2 Diabetes Mellitus.
Secondary ID [1] 314152 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Periodontal Disease 336984 0
Type 2 Diabetes Mellitus 336985 0
Condition category
Condition code
Oral and Gastrointestinal 333446 333446 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 333518 333518 0 0
Other inflammatory or immune system disorders
Metabolic and Endocrine 333519 333519 0 0
Diabetes

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Baseline and initial treatment visit (0-month; 1 hour duration)

Pre-operative periodontal charting recorded by registered periodontists or DClinDent postgraduate registrars, with a periodontal UNC-15 probe. All examiners will be calibrated.

This will allocate participants into the group categories:

Group #1: Periodontally Healthy groups

Group #2: Periodontitis (Generalised Stage III-IV) without diagnosed Type 2 Diabetes Mellitus

Group #3: Diagnosed T2DM (HbA1c greater than or equal to 6.5%)* with Periodontitis (Generalised Stage III-IV) (with and without systemic diseases);

*According to the American Diabetes Association 2022

Saliva, gingival crevicular fluid (GCF) and plaque samples will be collected from all Group #1, #2 and #3 patients

Participants will be asked to refrain from eating and drinking for at least one hour prior to saliva sample collection. At the appointment, participants will rinse their mouths with ~10 mL of water 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 will be 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 all patients: up to 6 paper strips will be collected each from 1 deepest site and 1 healthy site

All patients will be allocated the next available appointment for standard care, receiving supragingival and subgingival non-surgical debridement using hand scalers and ultrasonic instruments over 2-4 appointments (60-90 mins duration per appointment).

Follow-up reviews (3- and 6- mo post-periodontal treatment; 60-90 mins duration per appointment)

All periodontitis patients with and without T2DM will receive the non-surgical instrumentation for the management of periodontitis as per European Federation of Periodontology S3-level clinical practice guideline.

All periodontitis patients with and without T2DM will be recalled 3 months following debridement to re-assess periodontal parameters and recollect saliva, GCF and plaque (from the same sites as baseline appointment).

They will then receive the standard protocol of care, including oral hygiene instruction (OHI), non-surgical re-instrumentation of persistent sites and supragingival maintenance of remaining sites.

Patients will then be recalled at the 3-, 6- mo time points (since initial therapy)

Patient compliance with treatment reviews will be recorded using a clinic attendance checklist.

The diagnosis of extracellular vesicles (EVs) in periodontitis patients with and without diabetes will be compared to investigate the distinct mechanisms of disease pathogenesis related to EVs.

Please note that all patients will receive routine standard of care of non-surgical periodontal treatment (NSPT), with no specific additional intervention applied. It is an observational longitudinal prospective study, with follow-up to 3, 6 and 12 months post non-surgical periodontal treatment (NSPT) for all periodontitis patients with and without type II diabetes. Clinical parameters and saliva, GCF and subgingival plaque samples will be collected at baseline, 3-, 6-, and 12-month time points.
Intervention code [1] 330741 0
Diagnosis / Prognosis
Intervention code [2] 330742 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. Saliva, GCF and subgingival plaque samples will be collected once as no follow-up will be carried out for control groups.
Periodontally healthy patients are 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).

Anticipated duration of control group observation sessions (up to 60 mins)

Saliva, GCF and subgingival plaque samples will be collected at baseline, 3 -, 6 - and 12- months post initial periodontal therapy.

Unstimulated saliva will be collected from these patient controls

GCF and plaque samples: up to 6 paper strips will be collected each from 1 deepest site and 1 healthy site.
Control group
Active

Outcomes
Primary outcome [1] 341018 0
Levels of EVs particle numbers in GCF samples
Timepoint [1] 341018 0
Baseline, 3-, 6-, 12-months post routine periodontal treatment
Primary outcome [2] 341095 0
Levels of EVs particle numbers in saliva samples
Timepoint [2] 341095 0
Baseline, 3-, 6-, 12-months post routine periodontal treatment
Primary outcome [3] 341096 0
Levels of EVs particle numbers in subgingival plaque samples
Timepoint [3] 341096 0
Baseline, 3-, 6-, 12-months post routine periodontal treatment
Secondary outcome [1] 445823 0
Change in probing pocket depth (PPD)
Timepoint [1] 445823 0
Baseline, 3-, 6-, 12-months post routine periodontal treatment
Secondary outcome [2] 445824 0
Change in bleeding on probing (BOP)
Timepoint [2] 445824 0
Baseline, 3-, 6-, 12-months post routine periodontal treatment
Secondary outcome [3] 445825 0
Omics of EV microbiome profiles
Timepoint [3] 445825 0
Baseline, 3-, 6-, 12-month post routine periodontal treatment
Secondary outcome [4] 446263 0
Omics of EV proteome profiles
Timepoint [4] 446263 0
Baseline, 3-, 6-, 12-month post routine periodontal treatment

Eligibility
Key inclusion criteria
Patients 18 years of age or older.
Stage III-IV periodontitis patients will have interdental CAL greater than or equal to 5mm, PPD greater than or equal to 6mm, and significant radiographic bone loss.
*Based on Chapple et al 2018
For the T2DM group (n=25):
HbA1c greater than or equal to 6.5%*
*Based on American Diabetes Association 2022
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
T1DM + Gestational Diabetes
Long-term use of immunosuppressive or anti-inflammatory drugs, periodontal treatment or antibiotics therapy six months prior to investigation
Pregnancy, cardiovascular disease, active infectious disease
Smoking greater than or equal to 10 cigarettes/day*
*Based on Tonetti et al. 2018

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Convenience sample
Timing
Prospective
Statistical methods / analysis
For descriptive analysis of categorical data, absolute and relative frequencies will be calculated. The numerical data will be first assessed for approximate normality. Chi-square tests and one-way ANOVA will be 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 EVs or EV content changes over time in periodontal study groups (Uncontrolled T2DM and Non-diabetic/Well-controlled T2DM). This will be displayed in the form of a line graph showing trends over time.

The significance of differences (expression level of EVs and EV content) between periodontal study groups (with and without T2DM) 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 using paired Friedman test followed by post-tests.

Confidence interval 95% with p value < 0.05.

Multi-variate analyses will be conducted to adjust for confounders (smoking, plaque control, age, sex, ethnicity) and subanalysis of different staging of periodontitis.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
2/06/2025
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
75
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD

Funding & Sponsors
Funding source category [1] 318663 0
University
Name [1] 318663 0
School of Dentistry - University of Queensland
Country [1] 318663 0
Australia
Primary sponsor type
University
Name
School of Dentistry - University of Queensland
Address
Country
Australia
Secondary sponsor category [1] 321084 0
None
Name [1] 321084 0
Address [1] 321084 0
Country [1] 321084 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 317276 0
Metro North Health Human Research Ethics Committee B
Ethics committee address [1] 317276 0
Ethics committee country [1] 317276 0
Australia
Date submitted for ethics approval [1] 317276 0
15/07/2020
Approval date [1] 317276 0
17/03/2021
Ethics approval number [1] 317276 0
54584
Ethics committee name [2] 317279 0
The University of Queensland Human Research Ethics Committee A
Ethics committee address [2] 317279 0
Ethics committee country [2] 317279 0
Australia
Date submitted for ethics approval [2] 317279 0
24/03/2021
Approval date [2] 317279 0
13/04/2021
Ethics approval number [2] 317279 0
2018001225

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

Contacts
Principal investigator
Name 140538 0
Dr John Xiong
Address 140538 0
The University of Queensland, School of Dentistry, 288 Herston Road, Herston, 4006, QLD
Country 140538 0
Australia
Phone 140538 0
+61 0422559817
Fax 140538 0
Email 140538 0
[email protected]
Contact person for public queries
Name 140539 0
Dr Pingping Han
Address 140539 0
The University of Queensland, School of Dentistry, 288 Herston Road, Herston, 4006, QLD
Country 140539 0
Australia
Phone 140539 0
+617 336 58172
Fax 140539 0
Email 140539 0
[email protected]
Contact person for scientific queries
Name 140540 0
Prof Saso Ivanovski
Address 140540 0
The University of Queensland, School of Dentistry, 288 Herston Road, Herston, 4006, QLD
Country 140540 0
Australia
Phone 140540 0
+617 336 58064
Fax 140540 0
Email 140540 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.