Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000975493p
Ethics application status
Submitted, not yet approved
Date submitted
7/08/2025
Date registered
4/09/2025
Date last updated
4/09/2025
Date data sharing statement initially provided
4/09/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Bridging oral and systemic inflammation: Experimental gingivitis in patients with rheumatoid arthritis
Scientific title
Bridging Oral and Systemic Inflammation: Experimental Gingivitis in Rheumatoid Arthritis and Changes in Gingival Inflammation and Autoantibody Levels
Secondary ID [1] 315081 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 338475 0
Gingivitis 338557 0
Condition category
Condition code
Inflammatory and Immune System 334771 334771 0 0
Rheumatoid arthritis
Oral and Gastrointestinal 334862 334862 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
The comparators are:
1. Rheumatoid Arthritis Group - participants with diagnosed rheumatoid arthritis
2. At-Risk Group - participants who are positive for RA-related antibodies or have joint symptoms but no formal RA diagnosis
All participants will undergo a three-phase study:
1.. Baseline Phase (Day -14 to Day 0): Participants will receive a professional dental cleaning and be instructed to maintain optimal oral hygiene until there is no clinical evidence of gingivitis. This ensures a consistent baseline across participants.
2. Experimental Gingivitis Phase (Day 0 to Day 14–21): Participants will be asked to discontinue all oral hygiene practices (e.g., toothbrushing and flossing) for 14 to 21 days to induce gingivitis in a safe and controlled manner. No dietary restrictions will be imposed.
3. Resolution Phase (14 Days Post-Visit 4): Participants will resume regular oral hygiene practices. Clinical assessments will continue to monitor the resolution of gingival inflammation.
The study will consist of six visits: Visit 1 at Day –14, Visit 2 at Day 0, Visit 3 at Day 7, Visit 4 between Day 14 and Day 21, Visit 5 at 7 days post–Visit 4, and Visit 6 at 14 days post–Visit 4.
Visit 1: Periodontal measurements, biological sample collections (i.e. saliva, plaque and gingival crevicular fluid), provision of professional cleaning and oral hygiene instruction.
Visit 2: Periodontal measurements, biological sample collections (i.e. saliva, plaque, gingival crevicular fluid and blood).
Visit 3: Periodontal measurements, biological sample collections (i.e. saliva, plaque and gingival crevicular fluid).
Visit 4: Periodontal measurements, biological sample collections (i.e. saliva, plaque, gingival crevicular fluid, blood and gingival tissue).
Visit 5: Periodontal measurements, biological sample collections (i.e. saliva, plaque and gingival crevicular fluid).
Visit 6: Periodontal measurements, biological sample collections (i.e. saliva, plaque and gingival crevicular fluid) and provision of professional cleaning
Each visit may take up to one hour.
Intervention code [1] 331691 0
Other interventions
Intervention code [2] 331757 0
Behaviour
Comparator / control treatment
Healthy Control Group - systemically healthy individuals with no RA or related risk factors
Control group
Active

Outcomes
Primary outcome [1] 342414 0
Change in Gingival Inflammation Severity (Gingival Index, GI)
Timepoint [1] 342414 0
This primary outcome will be assessed at all time points for all participants: Visit 1 at Day –14, Visit 2 at Day 0 (commencement of experimental gingivitis), Visit 3 at Day 7, Visit 4 between Day 14 and Day 21, Visit 5 at 7 days post–Visit 4, and Visit 6 at 14 days post–Visit 4. With Visit 4 (End-induction assessment), timing is participant-specific and set by the clinician within this window based on clinical judgement.
Primary outcome [2] 342424 0
Change in Anti-Citrullinated Protein Antibodies (ACPA) Level in RA/At-Risk Participants
Timepoint [2] 342424 0
This primary outcome will be assessed in RA and at-risk participants at Visit 2 (Day 0 - commencement of experimental gingivitis) and Visit 4 (Day 14–21). With Visit 4 (End-induction assessment), timing is participant-specific and set by the clinician within this window based on clinical judgement.
Primary outcome [3] 342636 0
Changes in Rheumatoid Factor (RF) Level in RA/At-Risk Participants
Timepoint [3] 342636 0
This primary outcome will be assessed in RA and at-risk participants at Visit 2 (Day 0 - commencement of experimental gingivitis) and Visit 4 (Day 14–21). With Visit 4 (End-induction assessment), timing is participant-specific and set by the clinician within this window based on clinical judgement.
Secondary outcome [1] 450738 0
Change in Inflammatory Markers in Gingival Crevicular Fluid (GCF)
Timepoint [1] 450738 0
This secondary outcome will be assessed at all time points for all participants: Visit 1 at Day –14, Visit 2 at Day 0 (commencement of experimental gingivitis), Visit 3 at Day 7, Visit 4 between Day 14 and Day 21, Visit 5 at 7 days post–Visit 4, and Visit 6 at 14 days post–Visit 4. With Visit 4 (End-induction assessment), timing is participant-specific and set by the clinician within this window based on clinical judgement.
Secondary outcome [2] 450739 0
Change in Peripheral Blood Cytokine Profiles
Timepoint [2] 450739 0
This secondary outcome will be assessed in all participants at Visit 2 (Day 0 - commencement of experimental gingivitis) and Visit 4 (Day 14–21). With Visit 4 (End-induction assessment), timing is participant-specific and set by the clinician within this window based on clinical judgement.
Secondary outcome [3] 450740 0
Changes in Oral Microbial Composition
Timepoint [3] 450740 0
This secondary outcome will be assessed at all time points for all participants: Visit 1 at Day –14, Visit 2 at Day 0 (commencement of experimental gingivitis), Visit 3 at Day 7, Visit 4 between Day 14 and Day 21, Visit 5 at 7 days post–Visit 4, and Visit 6 at 14 days post–Visit 4. With Visit 4 (End-induction assessment), timing is participant-specific and set by the clinician within this window based on clinical judgement.
Secondary outcome [4] 450744 0
Neutrophil Extracellular Trap (NET) Markers in GCF or Blood
Timepoint [4] 450744 0
This secondary outcome will be assessed at all time points for all participants: Visit 1 at Day –14, Visit 2 at Day 0 (commencement of experimental gingivitis), Visit 3 at Day 7, Visit 4 between Day 14 and Day 21, Visit 5 at 7 days post–Visit 4, and Visit 6 at 14 days post–Visit 4. With Visit 4 (End-induction assessment), timing is participant-specific and set by the clinician within this window based on clinical judgement.
Secondary outcome [5] 450748 0
Flare Frequency and RA Symptom Changes (RA Group Only) - this will be assessed as a composite outcome
Timepoint [5] 450748 0
This secondary outcome will be assessed at all time points for all participants: Visit 1 at Day –14, Visit 2 at Day 0 (commencement of experimental gingivitis), Visit 3 at Day 7, Visit 4 between Day 14 and Day 21, Visit 5 at 7 days post–Visit 4, and Visit 6 at 14 days post–Visit 4. With Visit 4 (End-induction assessment), timing is participant-specific and set by the clinician within this window based on clinical judgement.
Secondary outcome [6] 450750 0
Transcriptomic Profile of Gingival Biopsies (Subset of RA)
Timepoint [6] 450750 0
This secondary outcome will be evaluated at Visit 4 (Day 14–21) in a selected subset of participants with RA. With Visit 4 (End-induction assessment), timing is participant-specific and set by the clinician within this window based on clinical judgement.
Secondary outcome [7] 450752 0
Time to Resolution of Gingival Inflammation After Resuming Hygiene
Timepoint [7] 450752 0
This secondary outcome will be assessed at all time points for all participants: Visit 1 at Day –14, Visit 2 at Day 0 (commencement of experimental gingivitis), Visit 3 at Day 7, Visit 4 between Day 14 and Day 21, Visit 5 at 7 days post–Visit 4, and Visit 6 at 14 days post–Visit 4. With Visit 4 (End-induction assessment), timing is participant-specific and set by the clinician within this window based on clinical judgement.
Secondary outcome [8] 451621 0
Time to Resolution of Gingival Inflammation After Resuming Hygiene
Timepoint [8] 451621 0
This secondary outcome will be assessed at all time points for all participants: Visit 1 at Day –14, Visit 2 at Day 0 (commencement of experimental gingivitis), Visit 3 at Day 7, Visit 4 between Day 14 and Day 21, Visit 5 at 7 days post–Visit 4, and Visit 6 at 14 days post–Visit 4. With Visit 4 (End-induction assessment), timing is participant-specific and set by the clinician within this window based on clinical judgement.

Eligibility
Key inclusion criteria
Inclusion Criteria for Control Group:
• 18 years or older, who can provide informed consent
• Systemically healthy individuals
• A dentition with a minimum of 24 permanent teeth
• Probing pocket depth less than or equal to 4mm at six sites/tooth
• Non-smoker/former smoker (quit greater than 6 months ago) only
• Willingness to comply with all study requirements and sign informed consent

Inclusion Criteria for Rheumatoid Arthritis Group:
• Adults aged 18-85 years
• Confirmed Rheumatoid Arthritis Diagnosis according to ACR/EULAR 2010 criteria
• A dentition with a minimum of 24 permanent teeth
• Probing pocket depth less than or equal to 4mm at six sites/tooth
• Non-smoker/former smoker (quit greater than 6 months ago) only
• Willingness to comply with all study requirements and sign informed consent

Inclusion Criteria for At-Risk Rheumatoid Arthritis Group:
• Adults aged 18-85 years
• Presence of anti-citrullinated protein antibodies or rheumatoid factor or arthralgia without clinical Rheumatoid Arthritis
• A dentition with a minimum of 24 permanent teeth
• Probing pocket depth less than or equal to 4mm at six sites/tooth
• Non-smoker/former smoker (quit greater than 6 months ago) only
• Willingness to comply with all study requirements and sign informed consent
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion Criteria for Control Group:
• Recent antibiotic or anti-inflammatory use within the past three months
• Using any antimicrobial mouthwashes during the study period
• Pregnant or lactating
• Orthodontic appliances or prostheses that affect gingival margins

Exclusion Criteria for Rheumatoid Arthritis Group:
• Other systemic diseases that could confound inflammation (e.g. uncontrolled diabetes, autoimmune overlap syndrome)
• Recent antibiotic use within the past three months
• Using any antimicrobial mouthwashes during the study period
• Pregnant or lactating
• Orthodontic appliances or prostheses that affect gingival margins

Exclusion Criteria for At-Risk Rheumatoid Arthritis Group:
• Other systemic diseases that could confound inflammation (e.g. uncontrolled diabetes, autoimmune overlap syndrome)
• Recent use of antibiotics within the past three months
• Using any antimicrobial mouthwashes during the study period
• Pregnant or lactating
• Orthodontic appliances or prostheses that affect gingival margins

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


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

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/10/2025
Actual
Date of last participant enrolment
Anticipated
30/09/2027
Actual
Date of last data collection
Anticipated
31/12/2027
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD

Funding & Sponsors
Funding source category [1] 319654 0
University
Name [1] 319654 0
The University of Queensland
Country [1] 319654 0
Australia
Primary sponsor type
University
Name
The University of Queensland
Address
Country
Australia
Secondary sponsor category [1] 322159 0
None
Name [1] 322159 0
Address [1] 322159 0
Country [1] 322159 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 318216 0
The University of Queensland Human Research Ethics Committee B
Ethics committee address [1] 318216 0
Ethics committee country [1] 318216 0
Australia
Date submitted for ethics approval [1] 318216 0
12/08/2025
Approval date [1] 318216 0
Ethics approval number [1] 318216 0

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

Contacts
Principal investigator
Name 143466 0
A/Prof Ryan Lee
Address 143466 0
The University of Queensland, School of Dentistry: 288 Herston Rd, Herston QLD 4006
Country 143466 0
Australia
Phone 143466 0
+0452491866
Fax 143466 0
Email 143466 0
[email protected]
Contact person for public queries
Name 143467 0
Miriam Lee
Address 143467 0
The University of Queensland, School of Dentistry: 288 Herston Rd, Herston QLD 4006
Country 143467 0
Australia
Phone 143467 0
+61733658013
Fax 143467 0
Email 143467 0
[email protected]
Contact person for scientific queries
Name 143468 0
Miriam Lee
Address 143468 0
The University of Queensland, School of Dentistry: 288 Herston Rd, Herston QLD 4006
Country 143468 0
Australia
Phone 143468 0
+61733658013
Fax 143468 0
Email 143468 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.