The Role of Functional Epigenetic Modifications in Peri-Implantitis

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

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

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.

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.