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Trial registered on ANZCTR


Registration number
ACTRN12623000606684p
Ethics application status
Not yet submitted
Date submitted
18/05/2023
Date registered
2/06/2023
Date last updated
2/06/2023
Date data sharing statement initially provided
2/06/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Treatment of early reversible gum disease using manuka oil
Scientific title
A randomized controlled trial evaluating effectiveness of a topical hydrogel containing Manuka oil in the treatment of human experimental gingivitis
Secondary ID [1] 309673 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gingivitis 330030 0
Condition category
Condition code
Oral and Gastrointestinal 326936 326936 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
This is an experimental gingivitis trial. The participants will receive gum health examination and a 20-minute professional cleaning at baseline and have to cease brushing and routine oral hygiene on 3-4 teeth of interest at the upper right side for 21 days to induce gingivitis. The gum health examination includes the following:
1. An assessment of gum redness and swelling (Gingival Index)
2. An assessment of plaque present on the study teeth (Plaque index)
3. The gap between gum and tooth (Periodontal Probing Depth)
4. Assessment of gum bleeding (Gingival bleeding index)
5. Photograph of teeth to determine color of teeth and gums
6. Collection of the gum fluid and plaque samples
Participants will be reviewed every week for 3 weeks prior to the establishment of experimental gingivitis.

On day 21, after experimental gingivitis has been established, all participants will receive a 20-minute professional cleaning after gum health examination. On the same appointment, the experimental group will be given the test medication, a carboxymethyl-cellulose gel containing manuka oil microspheres. They will be asked to self-administer approximately 1.0g of the gel twice daily, after toothbrushing, to the upper right posterior teeth by expressing the gel into the customised mouthguard and wearing this for 2 minutes. They will be asked to administer the gel for 3 weeks and gum health examination will be performed every week for 3 weeks.

All participants will be involved in a split mouth study design, comparing the gum health on the upper left (without gingivitis) and upper right (with induced gingivitis). Gum health examination will take place once every week for a total of 8 visits. Approximately 30 minutes will be required for each examination. The examination will be conducted by a registered dentist.

Adherence to intervention will be monitored in the dental undergraduate class which all the volunteers attend by recording responses in the attendance sheet.
Intervention code [1] 326113 0
Treatment: Other
Comparator / control treatment
It is a parallel arm study where the positive control group will follow the same protocol but will use a commercially-available 0.5% chlorhexidine gel, commonly used for treatment of gingivitis. The negative control group will follow the same protocol but will use a methyl-cellulose gel with no active ingredients. It is also a split mouth study, where 3-4 teeth will be the ‘test’ group and the contralateral teeth will be ‘controls’.

Participants in the ‘control’ group will refrain from brushing for 21 days to induce experimental gingivitis, similar to the ‘test’ group. The ‘control’ teeth at the contralateral side will be brushed as per normal routine throughout the study.
Control group
Active

Outcomes
Primary outcome [1] 334772 0
Gingival index (GI) (Loe and Silness 1963)
Timepoint [1] 334772 0
Day 1,7,14,21 (primary endpoint),28,35,42 post-baseline
Primary outcome [2] 334875 0
Gingival bleeding index (GBI) (Ainamo and Bay 1975)
Timepoint [2] 334875 0
Day 1,7,14,21 (primary endpoint),28,35,42 post-baseline
Secondary outcome [1] 422021 0
The objective shade change of teeth assessed using a colourimeter (OptiShade, StyleItaliano)
Timepoint [1] 422021 0
Day 1,21,42 post-baseline
Secondary outcome [2] 422308 0
The patient’s perception of the taste of the test products assessed with a visual analogue scale (VAS) (García-Gargallo et al. 2017)
Timepoint [2] 422308 0
Day 42 post-baseline
Secondary outcome [3] 422309 0
Duration of the flavor in mouth assessed with a visual analogue scale (VAS) (García-Gargallo et al. 2017)
Timepoint [3] 422309 0
Day 42 post-baseline
Secondary outcome [4] 422310 0
Taste sensation alteration assessed with a visual analogue scale (VAS) (García-Gargallo et al. 2017)
Timepoint [4] 422310 0
Day 42 post-baseline
Secondary outcome [5] 422311 0
Any adverse event such as teeth sensitivity, dry mouth, oral numbness, or burning sensation of mucosa as well as self-perceived discoloration of teeth assessed with a visual analogue scale (VAS) (García-Gargallo et al. 2017)
Timepoint [5] 422311 0
Day 42 post-baseline
Secondary outcome [6] 422312 0
Probing pocket depth measured with Williams probe
Timepoint [6] 422312 0
Day 1,7,14,21,28,35,42 post-baseline
Secondary outcome [7] 422313 0
Objective shade change of the gingiva assessed using a colourimeter (OptiShade, StyleItaliano)
Timepoint [7] 422313 0
Day 1, 21, 42 post-baseline
Secondary outcome [8] 422314 0
Analysis of gingival crevicular fluid and plaque samples, collected using Periopaper strip (OraFlow Inc., Amityville, NY) and a curette respectively
Timepoint [8] 422314 0
Day 1,21,42 post-baseline
Secondary outcome [9] 422398 0
Plaque index (Silness & Löe)
Timepoint [9] 422398 0
Day 1,7,14,21,28,35,42 post-baseline

Eligibility
Key inclusion criteria
Dental students in good health with at least 3 maxillary posterior teeth (premolar and molars) on each side, free of periodontal pockets of >3mm
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Have periodontitis or peri-implantitis, active dental caries, active infection in the oral cavity, had a history of allergy to honey or chlorhexidine products, had antibiotics or chlorhexidine mouthwash recently, wears a partial plate replacing upper teeth, undergoing orthodontic treatment, currently pregnant or nursing, a smoker or vaper.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The products will be given to the participants in opaque tubes packaged in pre-labelled brown paper envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Excel randomization tool
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
Efficacy
Statistical methods / analysis
The sample size is calculated by considering a=0.05; power = 90% for 3 study groups. The primary outcome is the sulcus bleeding index (SBI), for which a mean of 41.28 and a standard deviation of 18.13 were anticipated. A difference of 16.12 between the means was also expected, and thus, 20 participants per group were deemed necessary (Butera et al. 2021). Considering a drop out rate of 10%, we anticipated 66 participants altogether for 3 groups.

Statistical analysis will be conducted with SPSS. Kruskal-Wallis tests, Chi-square tests, non-parametric Kruskal-Wallis tests at the 0.05 level for all time points. ANOVA and Tukey’s post hoc tests, Mann-Whitney test

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/10/2023
Actual
Date of last participant enrolment
Anticipated
31/10/2023
Actual
Date of last data collection
Anticipated
31/12/2023
Actual
Sample size
Target
66
Accrual to date
Final
Recruitment outside Australia
Country [1] 25545 0
New Zealand
State/province [1] 25545 0
Otago

Funding & Sponsors
Funding source category [1] 313865 0
Government body
Name [1] 313865 0
Ministry of Business, Innovation and Employment
Country [1] 313865 0
New Zealand
Primary sponsor type
University
Name
University of Otago
Address
Faculty of Dentistry
University of Otago PO Box 56
Dunedin 9054 New Zealand
Country
New Zealand
Secondary sponsor category [1] 315703 0
None
Name [1] 315703 0
Address [1] 315703 0
Country [1] 315703 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 313014 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 313014 0
Ministry of Health
Health and Disability Ethics Committees PO Box 5013
Wellington 6140
Ethics committee country [1] 313014 0
New Zealand
Date submitted for ethics approval [1] 313014 0
15/06/2023
Approval date [1] 313014 0
Ethics approval number [1] 313014 0

Summary
Brief summary
The Global Burden of Disease Study of 2016 revealed that periodontal disease ranked as the 11th most widespread condition globally (Vos et al. 2017), affecting approximately 20% to 50% of the population (Baehni et al. 2010). Gingivitis is a reversible gingival inflammation caused by the accumulation of dental plaque at the gingival margin and may lead to occasional gingival bleeding (Armitage 2004). The mode of administration of local drug delivery is crucial in the oral cavity, besides the convenience of application, the drug-eluting material must remain stable under the persistent fluid flow (saliva) and withstand cyclic stresses caused by chewing activity. A Leptospermum scoparium essential oil-containing emulsion designed for application into the periodontal pocket can increase the substantivity and stabilize the essential oil (Porter et al. 2021).
The aim of this study is to evaluate the effectiveness of a locally applied hydrogel containing Manuka oil on experimentally induced gingivitis. 66 healthy 4th year dental students will be recruited. An intraoral scanning of the upper posterior teeth will be taken to fabricate a mouthguard. Participants receive professional tooth cleaning prior to the start of the trial, and then cease brushing their upper right teeth for 21 days. Gum inflammation will be measured weekly throughout the study. After 21 days, with gum inflammation established, the participants will then commence using the control or test medicament gels.
The experimental group will be given the test medication, a methyl-cellulose gel containing Manuka oil microspheres. They will be asked to self-administer approximately 1.0g of the gel twice daily to the upper right posterior teeth by expressing the gel into the customised mouthguard and wearing this for 2 minutes. The positive control group will follow the same protocol but will use a commercially-available 0.5% chlorhexidine gel. The negative control group will follow the same protocol but will use a methyl-cellulose gel with no active ingredients. Oral hygiene instructions will be given to all participants.
Participants will be examined at baseline then once every week for 6 weeks. All 7 examinations (Days 1, 7,14, 21, 28, 35, 42) will include the recording of clinical parameters: gingival index (GI) plaque index (PlI) probing pocket depth (PPD) and gingival bleeding index (GBI). The colour of the teeth and of the gingiva will be recorded and the gingiva crevicular fluid (GCF) and dental plaque samples will be collected at baseline, on Day 21 and Day 42. On day 42, participants will be given a questionnaire with a visual analogue scale (VAS) to assess their opinions on the gel. After the clinical trial, all subjects resume their normal oral hygiene procedures and will be reviewed once a month until the gingival clinical parameters return to the baseline.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 126682 0
Prof Warwick Duncan
Address 126682 0
Faculty of Dentistry
University of Otago
310 Great King Street North Dunedin Dunedin 9016
New Zealand
Country 126682 0
New Zealand
Phone 126682 0
+64 34797110
Fax 126682 0
Email 126682 0
[email protected]
Contact person for public queries
Name 126683 0
Warwick Duncan
Address 126683 0
Faculty of Dentistry
University of Otago
310 Great King Street North Dunedin Dunedin 9016
New Zealand
Country 126683 0
New Zealand
Phone 126683 0
+64 34797110
Fax 126683 0
Email 126683 0
[email protected]
Contact person for scientific queries
Name 126684 0
Warwick Duncan
Address 126684 0
Faculty of Dentistry
University of Otago
310 Great King Street North Dunedin Dunedin 9016
New Zealand
Country 126684 0
New Zealand
Phone 126684 0
+64 34797110
Fax 126684 0
Email 126684 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The data will only be shared among the investigator team and the participants.


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.