Clinical trial NCT02710903: IL29 and IL28B Variants Associated With Periodontal Disease Pathogenesis
Official title: IL29 and IL28B Variants Associated With Periodontal Disease Pathogenesis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Periodontitis
Keywords: Periodontitis
SNP
Pathogenesis
IL29
IL28B
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Institute of Dental and Craniofacial Research (NIDCR)
First posted: 2016-03-17
Enrollment: 79
Sex: ALL
Minimum age (years): 25
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: A maximum of 220 subjects with a minimum of 25 years will be recruited and examined for this 1-7 visit, up to 35 days research study: Subjects will be genotyped to identify variants of the interleukin-29 (IL29) and interleukin-28B (IL28B) genes and placed in one of the 4 groups: 50 subjects with dominant allelic variants with healthy periodontium, 50 subjects with dominant allelic variants with periodontitis, 50 subjects with IL29 (rs30461) or any of IL28B (rs11083519; rs8105790; rs8099917) single nucleotide polymorphism's (SNP) variants and healthy periodontium, and 50 subjects with IL29 (rs30461) or any of IL28B (rs11083519; rs8105790; rs8099917) SNP variants and periodontitis. Visits will consist of outpatient procedures including oral examinations, oral prophylaxis or periodontal scaling and root planing, collection of gingival crevicular fluid, dental plaque, saliva, and blood samples. Analysis will include salivary DNA isolation and pyrosequencing to determine IL29 and IL28B genotype, mediator analysis of gingival crevicular fluid, dendritic cell differentiation and inflammatory mediator analysis, and whole-genome shotgun sequencing plaque analysis. Clinical outcomes will include measurements of periodontal disease progression and inflammation, such as clinical attachment level (CAL), pocket depth (PD), bleeding on probing (BOP), gingival index (GI), and plaque index (PI).

Primary Objective: To determine the impact of IL29 and IL28B SNP variants on periodontal disease expression and local inflammatory response during stent-induced biofilm overgrowth.

Secondary Objective: To evaluate in vitro the impact of IL29 and IL28B SNP variants on cell-mediated, innate inflammatory response.


Eligibility criteria: Inclusion Criteria:

* Subjects must have read, understood and signed an informed consent form in English.
* Subjects must be able and willing to follow study procedures and instructions in English.
* Subjects must be non-Hispanic Caucasian.
* Subjects must be adult males or females with a minimum of 25 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 present with one of the following four categories to be considered for enrollment:
* Dominant IL28B and IL29 allelic with PD ≤4mm, no evidence of interproximal CAL, and \<20% of sites with BOP.
* Dominant IL28B and IL29 allelic with the presence of at least four periodontal sites with PD ≥ 5mm, evidence of interproximal CAL, and ≥20% of sites with BOP.
* IL28B or IL29 SNP variants with PD ≤4mm, no evidence of interproximal CAL, and \<20% of sites with BOP.
* IL28B or IL29 SNP variants with the presence of at least four periodontal sites with PD ≥ 5mm, evidence of interproximal CAL, and ≥20% of sites with BOP

Exclusion Criteria:

* 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.
* 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.
* 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 pocket depth (mm)
timeFrame: 21 days
measure: Change in clinical attachment level (mm)
timeFrame: 21 days
measure: Change in plaque index (0-3)
timeFrame: 21 days
measure: Change in bleeding on probing (Yes/No)
timeFrame: 21 days
measure: Change in gingival crevicular fluid interleukin-1 beta (GCF IL-1b)
timeFrame: 21 days
measure: Change in gingival crevicular fluid prostaglandin E2 (GCF PGE2)
timeFrame: 21 days
measure: Change in gingival crevicular fluid interleukin-29 (GCF IL-29)
timeFrame: 21 days
measure: Change in gingival crevicular fluid interleukin-28B (GCF IL-28B)
timeFrame: 21 days
measure: Change in gingival index (0-4)
timeFrame: 21 days
measure: Composition of the microbiota oral flora
timeFrame: 21 days
measure: Change in gingival crevicular fluid interleukin-6 (GCF IL-6)
timeFrame: 21 days
Secondary outcomes:
measure: Change in interleukin-29 expression in dendritic cells at day 35
timeFrame: 35 days
measure: Change in interleukin-28B expression in dendritic cells at day 35
timeFrame: 35 days
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: Jim Beck, PhD
role: PRINCIPAL_INVESTIGATOR
References: