Role of IL-37 Genetic Variants in Modulating Innate Immune Response to Periodontal Pathogens (ITS)

This study will provide mechanistic insight into the underlying causes and molecular level pathogenesis of periodontal diseases. We will identify key mechanisms that confer risk and protection. Ultimately this will lead to new and improved diagnostics and therapeutics. Because periodontal disease is a uniquely accessible biofilm-associated disease it will provide insight into many other diseases such as inflammatory bowel disease and chronic infections associated with indwelling catheters and artificial prostheses. Subjects with periodontal conditions will have therapeutic benefit from the treatments provided.

Study Overview

• Status: Completed
• Conditions: Periodontal Diseases

Detailed Description

A maximum of 440 subjects will be enrolled in this study with the goal of identifying 31 of each of the three types of IL-37 genotypes (93 total). Subject participation may include 1 to 9 visits lasting over a period of 6 months. Clinical data and medical history data will be collected at the screening visit to ascertain eligibility. Saliva collected at screening will be used to determine genotype. If one of the three targeted genotypes results, these patients will be assigned to the appropriate genotype group until 31 subjects are in each group at which point recruitment and screening will stop. There are no plans to share genotype classification with subjects. All subjects will have saliva and dental plaque collected at baseline. Twenty four of the 93 subjects (8 from each group) will be selected for gingival biopsy. These 24 subjects will have GCF samples collected at baseline. All subjects will have GCF samples collected at visit 3. Enrolled subjects (31 of each type of the three genotypes) will be recalled up to four additional times spread over twelve weeks for blood collection, to be used for monocyte isolation and whole blood stimulation. Gingival tissue samples will be used for immunohistochemistry, laser capture and RNA extraction. 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.

• Study Type: Observational
• Enrollment (Actual): 86

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Chapel Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

adult Caucasian male and female subjects recruited from the patients, students and staff at the University of North Carolina at Chapel Hill, as well as the general population in or near Chapel Hill NC.

Description

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 adult Caucasian males or females between the ages of 18 and 65 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.

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.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Group 1; IL-37 genotype 1.1
Group 2; IL-37 genotype 1.2
Group 3; IL-37 genotype 2.2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cytokines	Levels of key cytokines in gingival crevicular fluid.	6 weeks
Gingival Tissue Expression	Levels of IL-37 expressed in gingival tissue samples obtained during routine periodontal treatments.(Immunohistological)	Baseline
Whole Blood and Monocyte Cytokines	Evaluation of cytokine levels in LPS stimulated whole blood and monocytes	6 weeks
mRNA splice variants	Alternate IL-37 mRNA splice variants of gingival tissue among 1.1, 1.2, and 2.2	Baseline

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: National Institute of Dental and Craniofacial Research (NIDCR)
• Investigators: Principal Investigator: Silvana Barros, DDS PhD MS, University of North Carolina, Chapel Hill

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2015
• Primary Completion (Actual): May 24, 2019
• Study Completion (Actual): May 24, 2019

Study Registration Dates

• First Submitted: May 17, 2017
• First Submitted That Met QC Criteria: May 18, 2017
• First Posted (Actual): May 19, 2017

Study Record Updates

• Last Update Posted (Actual): September 25, 2019
• Last Update Submitted That Met QC Criteria: September 24, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Mouth Diseases; Periodontal Diseases
• Other Study ID Numbers: 15-0335; R01DE023836 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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