Clinical trial NCT03513497: IFI16 is a Periodontitis Modulating Protein
Official title: IFI16 is a Periodontitis Modulating Protein
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Severe Periodontitis
Acute Inflammatory Response
Keywords: Teeth
Periodontal disease
acute inflammatory response
stent-induced biofilm overgrowth
periodontal pathogens
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Institute of Dental and Craniofacial Research (NIDCR)
First posted: 2018-05-01
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: To characterize the expression of Interferon gamma inducible protein 16 (IFI16) and Absent in melanoma 2 (AIM2) in gingival tissues in an inflammatory response using an acrylic mouthguard (also referred to as a stent) induced bacteria overgrowth method.

Participants: A maximum of 72 Adult subjects will be recruited from the patients, students and staff at the University of North Carolina, as well as the general population in or near Chapel Hill NC.

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 (mouthguard), 2 gingival biopsies, 2 subgingival (below the gumline) plaque samples, and Scaling Root planing (SRP)/or adult prophylaxis

Detailed description: A total of 72 subjects will be enrolled. Specifically, a sufficient number of adults 18 years and older will be screened until 36 healthy (PPC-A) subjects and 36 subjects with severe periodontal disease (PPC-G) will be enrolled. Eligibility for study participation will be determined during the screening session. Barring dropout, subject participation will include 1 to 8 visits lasting over a maximum period of 42 days. The last 3 visits (visit 5-8) will depend on the individual need of the subject for providing SRP. Clinical data and medical history data will be collected at the screening visit to ascertain eligibility. All subjects will have dental plaque and a gingival biopsy collected at baseline. Enrolled subjects will be included in an experimental gingivitis model Stent-Induced Biofilm Overgrowth (SIBO) for 21 days. Individuals will return for safety checks every week during the 21-day period. At 21-days, plaque samples and a gingival biopsy will be collected. For diseased individuals SRP will initiate during the 21-day visit at the SIBO quadrant. Visit 6 (28 days) will include the post-biopsy follow up, prophylaxis (for healthy individuals) and SRP (diseased individuals). Subjects receiving SRP may have 2 additional visits (visit 7 at day 35 and visit 8 at day 42) for completing the SRP of all quadrants and will be dependent on individual need. Medical histories, demographics, height and weight, clinical and biological data described above will be recorded and stored on a secure server located at the University of North Carolina. Each participant enrolled into the study will have a unique identification number that has been stripped of any information that could be used by non-study members to identify the subject.

Eligibility criteria: Inclusion Criteria:

* Subjects must have read, understood and signed an informed consent form.
* Subjects must be able and willing to follow study procedures and instructions.
* Subjects must be adult males or females with a minimum of 18 years (inclusive).
* Subjects must present with at least 20 teeth in the functional dentition, excluding third molars.
* Subjects must have at least 3 teeth in each posterior sextant
* Subjects must be in good general health
* Subjects must be in the healthy (PPC-A) or severe periodontitis (PPC-G) categories according to the PPC (1)

Exclusion Criteria:

* If the sextants identified for the analysis has implants
* All individuals who meet criteria for anti-infective prophylaxis prior to dental procedures
* Chronic disease with oral manifestations including diabetes mellitus.
* Current smoker or one that has stopped smoking less than 2 years prior to enrollment.
* Gross oral pathology other than the periodontal disease.
* Treatment with antibiotics for any medical or dental condition within 1 month prior to the screening examination.
* Chronic treatment (i.e., two weeks or more) with any medication known to affect periodontal status (e.g., phenytoin, calcium antagonists, cyclosporin, coumadin, non-steroidal anti-inflammatory drugs, aspirin) within one month of the screening examination.
* Ongoing medications initiated less than three months prior to enrollment (i.e., medications for chronic medical conditions must be initiated at least three months prior to enrollment).
* Significant organ disease including impaired renal function, heart murmur, history of rheumatic fever or valvular disease, or any bleeding disorder.
* Individuals with prosthetic material used for intra-cardiac repair (e.g. for congenital heart disease), or intra-cardiac devices, cardiac transplant, infective endocarditis and individuals who have had previous infectious complications of prosthetic joint infections
* Infectious diseases such as hepatitis, HIV or tuberculosis.
* Anemia or other blood dyscrasias.
* Anticoagulant therapy or drugs, such as heparin or warfarin.
* Severe unrestored caries, or any condition that is likely to require antibiotic treatment over the trial.
* Pregnant, or expect to become pregnant within the next several months.
* Females of child-bearing capacity must be willing to have pregnancy test to confirm they are not pregnant.
* Females of child-bearing capacity not using any form of contraceptive methods
* Anything that would place the individual at increased risk or preclude the individual's full compliance with or completion of the study.

Primary outcomes:
measure: Change in Absent in Melanoma 2 (AIM2) mRNA Expression Levels
timeFrame: Baseline (Day 0), Visit 5 (Day 21)
measure: Change in Interferon Gamma Inducible Protein 16 (IFI16) mRNA Expression Levels
timeFrame: Baseline (Day 0), Visit 5 (Day 21)
measure: Change in the Percentage of AIM2 Positive Cells
timeFrame: Baseline (Day 0), Visit 5 (Day 21)
measure: Change in Percentage of Interferon Gamma Inducible Protein 16 (IFI16) Positive Cells
timeFrame: Baseline (Day 0), Visit 5 (Day 21)
Secondary outcomes:
measure: Correlation of Changes in Periodontal Pathogens With Changes of AIM2
timeFrame: Baseline (Day 0), Visit 5 (Day 21)
measure: Correlation of Changes in Periodontal Pathogens With Changes of IFI16
timeFrame: Baseline (Day 0), Visit 5 (Day 21)
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Julie T Marchesan, DDS, PhD
role: PRINCIPAL_INVESTIGATOR
References: