Metagenome Resilience in Experimental Gingivitis

Functional Metagenomic Characterisation of Resilience in Experimental Gingivitis

This study aims to identify new biomarkers that indicate the resilience of individuals to developing oral disease. An 'experimental gingivitis' model will be employed in which subjects will refrain from oral hygiene in one quadrant of their mouths for 3 weeks, and will then restore oral hygiene. Gum inflammation will be monitored by clinical measures throughout the trial and samples will be collected for analysis of microbial DNA and RNA.

Study Overview

• Status: Completed
• Conditions: Gingivitis; Oral Disease
• Intervention / Treatment: Behavioral: Partial abstinence from oral hygiene

Detailed Description

This project will employ an extended experimental gingivitis model to monitor changes in the oral metagenome and metatranscriptome during progression to gingivitis and recovery to oral health. The study will employ a 'split-mouth' design whereby one half of each individual's mouth is protected from oral hygiene while the other half acts as an internal control. Oral health status will be monitored through clinical measurements of dental plaque accumulation and gingival index. Plaque samples will be collected for DNA (metagenome) and RNA (metatranscriptome) sequencing. Using statistical modelling, genes and functional pathways will be identified that associate with resistance and resilience to gingivitis.

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• United Kingdom
  • Tyne And Wear
    • Newcastle upon Tyne, Tyne And Wear, United Kingdom, NE2 4BW
      • Dental Clinical Research Facility

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Gingivally healthy participants

Description

Inclusion Criteria:

• have read, understood and signed an informed consent form
• be adults of age 18 years or over
• have a minimum of 20 natural teeth (excluding third molars)
• be willing and able to comply with study procedures
• be a non-smoker and non-user of e-cigarettes or other oral intake nicotine replacement therapy (or have quit smoking/e-cigarettes/oral intake nicotine replacement therapy at least 2 years previously)
• healthy participants: good oral (no sites with interproximal attachment loss, GI ≥ 2.0 in ≤ 10% sites, %BOP scores ≤ 10%) and good general health.
• Covid-19 negative by LFT and fully vaccinated

Exclusion Criteria:

• infectious or systemic diseases that may be unduly affected by participation in this study
• extensive crown or bridge work and/or rampant decay at the discretion of the examiner
• wear removable partial dentures, a fixed/removable orthodontic appliance
• diabetes
• history of xerostomia, salivary gland disease, head and neck radiotherapy, Sjögren's syndrome, mucocutaneous disorders of the oral cavity, vesicobullous disorders of the oral cavity
• smoking or use of e-cigarettes within the last 2 years
• current use of prescription or over-the-counter medications that could affect salivary flow, at the discretion of the examiner
• lack of capacity to be able to consent to the research project and/or inability to follow study instructions
• pregnant by medical history or nursing
• currently undergoing or requiring extensive dental, orthodontic or implant treatment, or treatment for peri-implantitis
• treatment with antibiotics for any medical or dental condition within 4 weeks prior to enrolment
• scale and polish within 4 weeks prior to enrolment
• long term use of antibiotics or non-steroidal anti-inflammatory drugs (prophylactic low dose aspirin is permitted though)
• evidence of drug induced gingival overgrowth
• participation in a dental research study within the previous 20 days.
• Unilever personnel and personnel in the University department performing the study

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Experimental gingivitis; Group will wear a splint during oral hygiene to cover one quadrant of their dentition. They will develop gingivitis over 3 weeks. They will practise normal oral hygiene in the rest of their mouth (with minor restrictions, e.g. no mouthwash) and one other quadrant will act as an internal control for the gingivitis. After 3 weeks, normal oral hygiene will be restored throughout the mouth and subjects will continue to be monitored for a further 3 weeks.

Behavioral: Partial abstinence from oral hygiene; One quadrant of the dentition will be protected from oral hygiene for 3 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metagenomic sequence	Change from baseline	Intervals up to 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metatranscriptomic sequence	Change from baseline	Intervals up to 6 weeks
Lobene Modified Gingival Index: Min 0 - Max 4; Worse- higher score indicates more gingival inflammation	Change from baseline	Intervals up to 6 weeks
Plaque Index (Modified Quigley & Hein): Min 0 - Max 5; Worse - higher score indicates more plaque	Change from baseline	Intervals up to 6 weeks
Bleeding Index (Bleeding on probing): Min 0 - Max 1; Worse- higher score indicates a bleeding site	Change from baseline	Intervals up to 6 weeks

Collaborators and Investigators

• Sponsor: Newcastle University
• Collaborators: Newcastle-upon-Tyne Hospitals NHS Trust; Unilever SEAC
• Investigators: Study Director: Nicholas S Jakubovics, PhD, Newcastle University; Principal Investigator: Richard Holliday, PhD, Newcastle University

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2022
• Primary Completion (Actual): December 9, 2022
• Study Completion (Actual): December 9, 2022

Study Registration Dates

• First Submitted: May 18, 2022
• First Submitted That Met QC Criteria: May 18, 2022
• First Posted (Actual): May 25, 2022

Study Record Updates

• Last Update Posted (Estimate): January 30, 2023
• Last Update Submitted That Met QC Criteria: January 27, 2023
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Oral health; Metagenome; Dental plaque; Experimental gingivitis
• Additional Relevant MeSH Terms: Infections; Stomatognathic Diseases; Periodontal Diseases; Gingival Diseases; Gingivitis; Mouth Diseases
• Other Study ID Numbers: NU008913

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Anonymised participant demographics will be linked to the data: Year of birth, sex, ethnicity.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No