The Role of Functional Epigenetic Modifications in Peri-Implantitis

Study Overview
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Brief Summary
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The aim of this pilot, exploratory, single blind clinical trial is to evaluate the epigenetic changes associated with peri-implantitis.

Detailed Description
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Twenty patients will be voluntarily enrolled in two groups: 10 healthy participants, and 10 participants with peri-implantitis. Periodontal and peri-implant clinical and radiographic measurements, as well as body mass index, medical and dental history will be recorded within the following timelines: at baseline (for both groups), and 6 months after baseline for the peri-implantitis group only. At baseline, gingival biopsies and blood will be harvested from: a) healthy gingival sites during either surgical removal of wisdom teeth or gingivoplasty, in the healthy group; and, b) from a peri-implantitis site during surgical treatment of peri-implantitis, and when possible, from a healthy gingival site within the same participant, in the peri-implantitis group. After harvesting of biopsies, peri-implantitis subjects will be re-evaluated 6 months after treatment. During the 6-month visit, if a second surgical treatment of peri-implantitis in the same implant treated at baseline is indicated as standard of care of the participant, a new gingiva biopsy and blood will be collected. Gingival biopsies and blood collected from each participant will be used to perform DNA methylation analysis.

Official Title
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The Role of Functional Epigenetic Modifications in Peri-Implantitis: A Pilot Clinical Study

Conditions
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Periimplantitis

Intervention / Treatment
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* Procedure: Gingival biopsy and blood sample collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: General Inclusion Criteria: Subjects must have read, understood, and signed an informed consent form. Subjects must be 20-90 years of age. Subjects must be non-smokers or ex-smokers who have quit smoking for at least one year prior to enrollment in the study. Subjects must be in good general health as assessed by the Investigator. Healthy Periodontal Subjects Inclusion Criteria: In addition to the general inclusion criteria, a healthy periodontal subject must meet all of the following criteria: • Subjects show gingival health and no history of periodontitis, as described in the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. Peri-implantitis Subjects Inclusion Criteria: In addition to the general inclusion criteria, a PIT subject must meet all of the following criteria: Subjects with implant-supported prosthesis/es in function for at least 12 months who had at least one implant diagnosed with peri-implantitis based on the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. Subjects must be committed to the study and the required follow-up visits. Standard of care treatment of the diseased implant with PID will consist on open flap debridement (OFD). Exclusion Criteria: General Exclusion Criteria: Pregnant or lactating. Use of antibiotics, within 1 month before enrollment in the study. Chronic use of nonsteroidal anti-inflammatory drugs for over 3 weeks of continuous use at the time of enrollment or during the course of the study. Requirement for prophylactic antibiotics for dental procedures. Mucosal diseases in the localized area around the biopsy site. Subjects with a systemic disease that would preclude biopsy/oral surgery. History of local irradiation therapy in the head/neck area. Subjects with poor oral hygiene. Subjects receiving, or having a history of receiving intravenous or subcutaneous anti-resorptive agents associated with osteonecrosis of the jaw. Subjects with any untreated endodontic lesions or untreated periodontal disease adjacent to the biopsy site. Acute necrotizing ulcerative gingivitis or gross tooth decay, as determined by the investigator. Subjects with conditions or circumstances, in the opinion of the investigator, which would prevent completion of study participation or interfere with analysis. Periodontally Healthy Subjects Exclusion: In addition to the general exclusion criteria, subjects allocated to the healthy group who meet any of the following criteria will be excluded from participation in this study: • Root fragments, pericoronitis, endo-perio lesions, gross tooth decay, or other dental abscesses at the biopsy site. Subjects may be rescreened after resolution of these dental conditions. Peri-implantitis subjects Exclusion: In addition to the general exclusion criteria, subjects allocated to the PIT group who meet any of the following criteria will be excluded from participation in this study: Inadequate implant position (i.e., prosthetically driven). PIT due to excess of cement. Subjects who have physical or mental handicaps that would interfere with the ability to perform adequate oral hygiene. Subjects with implants previously surgically treated for PIT. Less than 2mm of keratinized peri-implant tissue.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Peri-implantitis<br>Patients undergoing surgical treatment for peri-implantitis. Gingival and blood samples will be collected during the treatment for peri-implantitis. | Procedure: Gingival biopsy and blood sample collection<br>* Gingival and blood samples will be collected.<br>|
| Healthy<br>Healthy patients undergoing treatment for either wisdom tooth extraction or gingivectomy. Gingival and blood samples will be collected during either wisdom tooth extraction or gingivectomy. | Procedure: Gingival biopsy and blood sample collection<br>* Gingival and blood samples will be collected.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in epigenetic signatures in peri-implantitis subjects as compared to healthy subjects, in an exploratory manner. (Gingival biopsies and blood collected to perform DNA methylation analysis) | Gingival and blood samples collected from healthy subjects and subjects with peri-implantitis will be used to determinate epigenetic signatures associated with peri-implantitis. | 6 months | 
| Epigenetic signatures associated with response to treatment peri-implantitis at 6 months, in an exploratory manner. (Differences in epigenetic signatures in peri-implantitis subjects as compared to healthy subjects, in an exploratory manner. | Samples collected from patients with peri-implantitis will be used to determinate epigenetic signatures associated response to treatment peri-implantitis at 6 months. (Gingival biopsies and blood collected to perform DNA methylation analysis) | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analog Scale (VAS) will be assessed to determinate patient-reported outcome measures, at baseline and at 6 months. | A visual analog scale (VAS) will be used to evaluate patient's pain/discomfort, esthetic satisfaction, and the subjects' overall satisfaction at baseline and at 6 months. | 6 months | 
| Oral Health Impact Profile-14 (OHIP-14) will be assessed to determinate patient-reported outcome measures, at baseline and at 6 months. | Oral Health Impact Profile-14 (OHIP-14) assessed at baseline and at 6 months. | 6 months | 
| Changes in peri-implant pocket depths (PPD) (in mm) from baseline to 6 month after surgery (only peri-implantitis group). | Peri-implant pocket depths (PPD) will be assessed at baseline and 6 month after surgery. | 6 months | 
| Changes in peri-implant BOP (in percentage), from baseline to 6 month after surgery (only peri-implantitis group). | Peri-implant BOP (in percentage) will be assessed at baseline and 6 month after surgery. | 6 months | 
| Percentage of peri-implant pocket closure at to 6 month after surgery (only peri-implantitis group). | Percentage of peri-implant pocket closure will be assessed at at to 6 month after surgery. | 6 months | 
| Changes in peri-implant marginal bone level (in mm) from baseline to 6 month after surgery (only peri-implantitis group). | Mean crestal bone level change around the implants will be determined by periapical radiographs of mesial and distal bone levels from baseline to 6 months surgery. | 6 months | 
| Change in soft tissue levels (in mm) from baseline to 6 month after surgery (only peri-implantitis group). | Soft tissue levels assessed at baseline and 6 months post-surgery in implants with peri-implantitis. | 6 months | 
| Incidence of post-operative surgical site infections (only peri-implantitis group). | Number of post-operative surgical site infections from surgery to 6 months. | 6 months | 
| Incidence of post-operative complications (only peri-implantitis group). | Number of post-operative complications from surgery to 6 months. | 6 months |