Atlas of Experimental Gingivitis in Humans (ATL)

An Atlas of Experimental Gingivitis in Humans at Single Cell Resolution

Pilot case series with a split-mouth design to track subjects with known exposure (dental biofilm accumulation) over 21 days. Descriptive design, using single cell RNA sequencing as a "digital biopsy" to catalog and contrast inflamed versus non-inflamed tissues from within the same mouth and across patients. Specimens (human) will biobanked from the 'digital biopsy' site for future analysis, including: Gingival crevicular fluid, oral epithelial stem/progenitor cells, and plaque samples, for 'omics analyses including metabolomics, microbiomic, and genomic data.

Study Overview

• Status: Completed
• Conditions: Gingivitis
• Intervention / Treatment: Procedure: Stent-Induced Biofilm Overgrowth

Detailed Description

Purpose is to conduct the first study of human gingiva in health and after biofilm-induced inflammation in the gingiva using scRNAseq. The pilot will involve induction of experimental gingivitis in all participants.

Participants include recruitment of 6 participants. Following consenting, screening, and enrollment, a customized acrylic stent will be used only on the selected sextant/teeth specified in the protocol, and only during tooth brushing to prevent oral hygiene in selected sextant/teeth. After the completion of the 3-week gingivitis induction phase, participants will enter a 2 week resolution phase. In the resolution phase, participants will reinstate full mouth oral hygiene, with the exception of flossing. Oral prophylaxis will be performed to regain health. During the 3 week gingivitis induction phase, participants will be required to return to the clinic every 7 days for safety checks.

Study Procedures (methods): Medical history, demographics (height/weight), urine based pregnancy test, vital signs (to include blood pressures, and pulse), standard dental clinical measures (to include plaque index, gingival index, bleeding on probing, and clinical attachment level), alginate impressions taken for fabrication of an acrylic stent (mouth guard), 2 gingival biopsies, 4 subgingival (below the gum line) plaque samples, 4 Gingival Crevicular Fluid (naturally occurring fluid between the gum and teeth) samples, and adult prophylaxis

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Adams School of Dentistry

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult males or females between the age of 18 and 30 years.
• Non-diabetic and no history of smoking within the last 5 years.
• Have read, understood and signed an informed consent form.
• Must be able and willing to follow study procedures and instructions.
• Must have at least 3 natural adjacent teeth in both maxillary (top) posterior sextants that will be selected for baseline gingival biopsy and SIBO gingival biopsy.
• Must be in good general health, as evidenced by medical hx (exclusion conditions defined under subject exclusion criteria below).
• Females of childbearing capacity must be willing to have pregnancy test to confirm they are not pregnant.

Exclusion Criteria

• History of intravenous bisphosphonates.
• Current or history (less than 5 years) of tobacco use in any form prior to enrollment (self-report)
• Chronic disease with oral manifestations including diabetes mellitus.
• Infectious disease such as hepatitis, HIV, or tuberculosis.
• Anemia or other blood dyscrasias.
• Currently taking anticoagulant therapy or drugs, such as heparin or warfarin.
• Those requiring antibiotic prophylaxis prior to dental treatment
• Exhibiting gross oral pathology or a history of periodontal disease.
• Individuals with a history or are currently using birth control containing hormones.
• Individuals without a history (less than 1 year) of regular professional oral health care, including prophylaxis. (self-report)
• Pregnant, breastfeeding or planning for pregnancy within 3 months.
• Individuals who used antibiotics/chronically used NSAIDs
• Anything that would place the individual at increased risk or preclude the individual's full compliance with or completion of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Healthy Volunteers; Enrolled subjects will be included in an experimental gingivitis model (SIBO) for 21 days and use an acrylic stent fabricated before and dispensed at the baseline appointment	Procedure: Stent-Induced Biofilm Overgrowth; Customized acrylic dental (sextant) stent will be used during brushing for 21 days to influence reversible gingival tissue inflammation.; Other Names: Dental Stent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Composition of Human Gingival Tissue at Day 1	Percentage of the human gingival biopsies that are epithelial, immune, or mesenchymal cells in health.	Day 1
Percent Composition of Human Gingival Tissue at Day 21	Percentage of the human gingival biopsies that are epithelial, immune, or mesenchymal cells during inflammation.	Day 21
Percent Composition of Human Gingival Epithelial Cells at Day 1	Percentage of the human gingival epithelial cell subtypes that are present (i.e. keratinocytes, Langerhans cells, etc.) in health.	Day 1
Percent Composition of Human Gingival Epithelial Cells at Day 21	Percentage of the human gingival epithelial cell subtypes that are present (i.e. keratinocytes, Langerhans cells, etc.) during inflammation.	Day 21
Percent Composition of Human Gingival Immune Cells at Day 1	Percentage of the human immune cell subtypes that are present (i.e. CD4, CD8, etc.) in health.	Day 1
Percent Composition of Human Gingival Immune Cells at Day 21	Percentage of the human immune cell subtypes that are present (i.e. CD4, CD8, etc.) during inflammation.	Day 21
Percent Composition of Human Gingival Mesenchymal Cells at Day 1	Percentage of the human mesenchymal cell subtypes that are present (i.e. stromal endothelial, etc.) in health.	Day 1
Percent Composition of Human Gingival Mesenchymal Cells at Day 21	Percentage of the human mesenchymal cell subtypes that are present (i.e. stromal endothelial, etc.) in health.	Day 21
Genes Expressed In Epithelial Cells at Day 1	Gene expression will be ranked by highest to lowest and a list of the top 100 genes in epithelial cells in health will be produced.	Day 1
Genes Expressed In Epithelial Cells at Day 21	Gene expression will be ranked by highest to lowest and a list of the top 100 genes in epithelial cells during inflammation will be produced.	Day 21
Genes Expressed In Immune Cells at Day 1	Gene expression will be ranked by highest to lowest and a list of the top 100 genes in immune cells in health will be produced.	Day 1
Genes Expressed In Immune Cells at Day 21	Gene expression will be ranked by highest to lowest and a list of the top 100 genes in immune cells during inflammation will be produced.	Day 21
Genes Expressed In Mesenchymal Cells at Day 1	Gene expression will be ranked by highest to lowest and a list of the top 100 genes in mesenchymal cells in health will be produced.	Day 1
Genes Expressed In Mesenchymal Cells at Day 21	Gene expression will be ranked by highest to lowest and a list of the top 100 genes in mesenchymal cells during inflammation will be produced.	Day 21
Genes Expressed In Epithelial Cell Subtypes at Day 1	Gene expression will be ranked by highest to lowest and a list of the top 100 genes in epithelial cell subtypes in health will be produced.	Day 1
Genes Expressed In Epithelial Cell Subtypes at Day 21	Gene expression will be ranked by highest to lowest and a list of the top 100 genes in epithelial cell subtypes during inflammation will be produced.	Day 21
Genes Expressed In Immune Cell Subtypes at Day 1	Gene expression will be ranked by highest to lowest and a list of the top 100 genes in immune cell subtypes in health will be produced.	Day 1
Genes Expressed In Immune Cell Subtypes at Day 21	Gene expression will be ranked by highest to lowest and a list of the top 100 genes in immune cell subtypes during inflammation will be produced.	Day 21
Genes Expressed In Mesenchymal Cell Subtypes at Day 1	Gene expression will be ranked by highest to lowest and a list of the top 100 genes in mesenchymal cell subtypes in health will be produced.	Day 1
Genes Expressed In Mesenchymal Cell Subtypes at Day 21	Gene expression will be ranked by highest to lowest and a list of the top 100 genes in mesenchymal cell subtypes during inflammation will be produced.	Day 21

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: Sunstar, Inc.
• Investigators: Principal Investigator: Kevin M Byrd, DDS, PhD, Adams School of Dentistry, UNC Chapel Hill

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 15, 2019
• Primary Completion (ACTUAL): December 3, 2019
• Study Completion (ACTUAL): December 3, 2019

Study Registration Dates

• First Submitted: September 24, 2019
• First Submitted That Met QC Criteria: September 24, 2019
• First Posted (ACTUAL): September 26, 2019

Study Record Updates

• Last Update Posted (ACTUAL): August 12, 2020
• Last Update Submitted That Met QC Criteria: August 10, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Stomatognathic Diseases; Periodontal Diseases; Mouth Diseases; Gingival Diseases; Gingivitis
• Other Study ID Numbers: 19-0183

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Single-cell RNA sequencing data will be shared through the Gene Expression Omnibus (GEO), a public functional genomics data repository supporting MIAME-compliant data submissions, which accepts sequence-based data. Gene list data will be searchable, cell by cell, through an online database. The files will be deposited both as raw reads (.fastq) and differential gene expression (.txt and .xlsx). Once data have been cleaned, assessed for differential gene expression, and validated by FISH/IHC, data will be made public. This will allow us to make this data freely available for others to investigate and reanalyze for their own purposes to accelerate further discoveries.
• IPD Sharing Time Frame: Gene expression data will be available for download once the manuscript has been accepted for publication.
• IPD Sharing Access Criteria: Gene expression lists by cell types will be provided to download freely in association with available journal access.

Drug and device information, study documents

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