Individual Variability of Experimental Gingivitis Response

Sponsor

King's College London (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05656417

Collaborator

Unilever R&D (Industry), Guy's and St Thomas' NHS Foundation Trust (Other), Biotechnology and Biological Sciences Research Council (Other)

Enrollment

Location

Anticipated Duration (Months)

9.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study aims to investigate the genetic cause of the variability between individuals seen in the development of the gum disease, gingivitis. This will be carried out through a 3 week programme where all oral hygiene is ceased, allowing 'experimental gingivitis' to develop, followed by a period of recovery when tooth cleaning is restored. Clinical assessments and biological samples will be taken during the course of the study for further analysis.

Condition or Disease	Intervention/Treatment	Phase
Gingivitis Oral Disease	Behavioral: Temporary cessation of all oral hygiene

Detailed Description

The purpose of the project is to investigate the factors which influence the oral disease, gingivitis. Gingivitis is the inflammation (swelling, redness, pain) of the gums, caused by the build-up of bacteria in the mouth. Research shows that the severity, extent and rate of development of gingivitis varies considerably between individuals. The aim of this project therefore is to investigate if an individual's DNA contributes to this range in outcomes and what impact it has on the human and bacterial cells in the mouth. This will be investigated through a period where all tooth brushing and oral hygiene will cease, and the changes in the mouth measured as the temporary 'experimental gingivitis' develops. Clinical measurements will include plaque build-up, levels of inflammation and bleeding scores, while samples of blood, saliva and plaque will be used to quantify changes in inflammatory markers and bacterial community composition.

Study Design

Study Type:

Observational

Anticipated Enrollment :

56 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Individual Variability of Experimental Gingivitis Response: a Parallel-group Cohort Study

Anticipated Study Start Date :

Dec 1, 2022

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Haplotype 1 Participants will attend a screening visit where they will provide a saliva sample for DNA sequencing. Participants will then be separated into two groups based on their gene profile. Participants in Group 1 will have a specific haplotype of the gene of interest. The groups will undergo a 2-week period of thorough oral hygiene and prophylactic treatment to achieve excellent gingival health. Participants in both groups will then cease all oral hygiene for a period of 3 weeks, where a state of gingivitis will develop. At the end of the 3 weeks, normal oral hygiene will be reinstated and prophylactic treatment offered as required for a further 2 weeks.	Behavioral: Temporary cessation of all oral hygiene Participants will refrain from all oral hygiene for 3 weeks. Other Names: Experimental gingivitis
Haplotype 2 Participants will attend a screening visit where they will provide a saliva sample for DNA sequencing. Participants will then be separated into two groups based on their gene profile. Group 2 will comprise of participants who possess a second distinct haplotype in the same gene of interest as Group 1. This group will undergo the same study procedures as Haplotype Group 1.	Behavioral: Temporary cessation of all oral hygiene Participants will refrain from all oral hygiene for 3 weeks. Other Names: Experimental gingivitis

Arm

Intervention/Treatment

Haplotype 1

Participants will attend a screening visit where they will provide a saliva sample for DNA sequencing. Participants will then be separated into two groups based on their gene profile. Participants in Group 1 will have a specific haplotype of the gene of interest. The groups will undergo a 2-week period of thorough oral hygiene and prophylactic treatment to achieve excellent gingival health. Participants in both groups will then cease all oral hygiene for a period of 3 weeks, where a state of gingivitis will develop. At the end of the 3 weeks, normal oral hygiene will be reinstated and prophylactic treatment offered as required for a further 2 weeks.

Behavioral: Temporary cessation of all oral hygiene

Participants will refrain from all oral hygiene for 3 weeks.

Other Names:

Experimental gingivitis

Haplotype 2

Participants will attend a screening visit where they will provide a saliva sample for DNA sequencing. Participants will then be separated into two groups based on their gene profile. Group 2 will comprise of participants who possess a second distinct haplotype in the same gene of interest as Group 1. This group will undergo the same study procedures as Haplotype Group 1.

Behavioral: Temporary cessation of all oral hygiene

Participants will refrain from all oral hygiene for 3 weeks.

Other Names:

Experimental gingivitis

Outcome Measures

Primary Outcome Measures

Löe-Silness Gingival Index: Min 0 - Max 3; Higher score indicates more gingival inflammation and a worse outcome. [Intervals over 6 weeks.]
Change from baseline.

Secondary Outcome Measures

Silness-Löe Plaque Index: Min 0 - Max 3; Higher score indicates more plaque accumulation and a worse outcome. [Intervals over 6 weeks.]
Change from baseline.
Bleeding on Probing: Min 0 - Max 1; Higher score indicates bleeding at the gingival site and a worse outcome. [Intervals over 6 weeks.]
Change from baseline.
Microbial dysbiosis (detection and counts of subgingival microbes). [Intervals over 6 weeks.]
Change from baseline.
Inflammatory markers (e.g. matrix metalloproteinase-8 and IL-1β) in blood, gingival crevicular fluid and saliva samples: Higher levels indicate a greater degree of gingival inflammation. [Intervals over 6 weeks.]
Change from baseline. Measured by enzyme-linked immunosorbent assay (units: ng/mL) in each sample type.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 35 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Age 18 to 35
Caucasian
No history of periodontitis/periodontal treatment (based on self-reported history)
Medical history clear of cardiovascular disease, diabetes, cerebrovascular disease, kidney or liver disease, cancer, HIV, Tuberculosis and Hepatitis C (self-reported)
Never smoker, e-cigarettes or nicotine gum use (self-reported). Individuals who rarely socially smoked more than 5 years ago would be permitted to participate.
Minimum of 24 teeth present
Be willing and competent (verbally and cognitively) to give written informed consent and complete a medical history form
Be willing and physically able to carry out all study procedures
Not have had a scale and prophylaxis in the previous month or have one scheduled prior to the end of the study
Participant in good periodontal health, based on:

absence of interproximal probing pocket depths (PPD) and clinical attachment level (CAL) > 3mm (with the exception of distal surfaces of third molars in the presence of impacted third molars) at the screening visit.
bleeding on probing (BOP) < 30% at the Screening visit and BOP <10% at Day -7.

Exclusion Criteria:

Currently taking part in other clinical trials
Pregnant or breastfeeding women
Taking medications including systemic anti-inflammatory medication within 3 months of the study (NSAIDs, no more than once per week and not in the week before sample collection, is permitted)
Systemic antibiotic intake within 6 months
Psychiatric conditions affecting participation in the study
The participant is also a member of staff who is part of the study team
Current orthodontic treatment
Regular consumption of alcohol exceeding the government recommended levels
Denture wearer/presence of dental implants/bridges
Have oral piercings
Obvious signs of untreated caries
Taking dietary supplements (e.g. multivitamins; antioxidants; fish oils)