Characterizing the Inflammation Around Dental Implants

Study Overview
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Brief Summary
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The use of titanium dental implants has become a common modern treatment to restore teeth. Although the success rate of dental implants is high, inflammation around the dental implant still occurs. The current study will investigate if the inflammation around the implant is due to bacterial infection, hypersensitivity or both. The goal of this cross-sectional study is to (1) Establish the levels of cytokines in peri-implant crevicular fluid associated with bacterial infection and hypersensitivity reaction; (2) Compare the levels of cytokines associated with hypersensitivity and bacterial infection between healthy implants and inflamed implants (peri-mucositis and peri-implantitis); (3) Determine whether the difference in the levels of cytokines, if they exist, reflects the clinical diagnosis of healthy implants and inflamed implants.

Detailed Description
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The main objective of this study is to: Establish the levels of cytokines in peri-implant crevicular fluid associated with bacterial infection (Type 1 and 3: IL-1, IL-6, IL-12, IL-17, IL-23, GM-CSF, IFN-γ, TNF-α), hypersensitivity reaction (Type 2: IL-4, IL-5, and IL-13) and the level of MMPs and including MMP-1, MMP-2, MMP-3, MMP-9 and MMP-13. Compare the levels of cytokines associated with hypersensitivity and bacterial infection between healthy implants and inflamed implants (peri-mucositis and peri-implantitis). Determine whether the difference in the levels of cytokines, if they exist, reflects the clinical diagnosis of healthy implants and inflamed implants. Secondary objectives includes: Measure the volume of peri-implant crevicular fluid and compare it between healthy implants and inflamed implants (peri-mucositis and peri-implantitis). Investigate the association between the levels of cytokines and the severity of inflammatory responses. Show how levels of cytokines influence the severity of inflammatory responses.

Official Title
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Characterizing the Inflammation Around Dental Implants: Bacterial Infection, Hypersensitivity, or Both?

Conditions
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Peri-Implantitis, Peri-implant Mucositis, Implant Site Reaction, Implant Site Infection, Hypersensitivity, Implant Site Rash, Implant Infection

Intervention / Treatment
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* Diagnostic Test: Clinical examination of a dental implant
* Diagnostic Test: Radiological Examination
* Diagnostic Test: Peri-implant crevicular fluid sample collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Received at least one functional implant (implant restored with a prothesis); Did not receive peri-implant mucositis and peri-implantitis treatment in the past three months. Exclusion criteria: Dental records with incomplete information; Individuals with a weak immune system or chronic disease such as diabetes, heart, lung or kidney disease; Pregnant women; Individuals undergoing orthodontic therapy and those who have oral piercing. History of diseases that modify or suppress the immune and inflammatory response, including rheumatoid arthritis, diabetes, lupus, and inflammatory bowel disease and metastatic cancer; Taking medications that cause antiresorptive osteonecrosis of the jaw (including any dose of intravenous bisphosphonates, oral bisphosphonate intake for more than three years, receptor activator of nuclear factor kappa-B ligand inhibitors, or antiangiogenic medications); Taking medications known to induce gingival hyperplasia including anticonvulsants, immunosuppressants, or calcium channel blockers; Taking steroid medications, systemic or local antibiotics in the last three months (as this may affect the interleukins activity); Received radiation therapy to the head and neck or chemotherapy; Received treatment to manage an inflamed implant, including management of peri-implantitis and peri-implant mucositis in the last three months.

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Functional Dental Implant<br>An implant restored with a prothesis and in function for a minimum of one year. | Diagnostic Test: Clinical examination of a dental implant<br>* Clinical examination includes bleeding on probing, pocket depth, gingival biotype, suppuration, gingival index<br>Diagnostic Test: Radiological Examination<br>* A standardized periapical radiograph in parallax technique will be taken.<br>Diagnostic Test: Peri-implant crevicular fluid sample collection<br>* A sample of the peri-implant crevicular fluid will be collected using paper strip for 60 seconds. The sample of the fluid will be a resultant of inserting six different strips at the same time in six sites of the implant including mesiobuccal, midbuccal, distobuccal, distopalatal/distolingual, midpalatal/midlingual, mesiopalatal/mesiolingual sites of the implant.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Health status of the implant | Classifying the implant into healthy implant, peri-implant mucositis and peri-implantitis according to the 2017 World Workshop (Berglundh et al. 2018). | Baseline (Cross-sectional) | 
| Levels of inflammatory mediators in Periimplant crevicular fluid | Establishing the the levels of cytokines in peri-implant crevicular fluid associated with bacterial infection (Type 1 and 3: IL-1, IL-6, IL-12, IL-17, IL-23, GM-CSF, IFN-γ, TNF-α), hypersensitivity reaction (Type 2: IL-4, IL-5, and IL-13) and the level of MMPs and including MMP-1, MMP-2, MMP-3, MMP-9 and MMP-13. | Baseline (Cross-sectional) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gingival Crevicular fluid volume | Measuring the volume of peri-implant crevicular fluid using Periotron device. The measurement unit is μL. | Baseline (Cross-sectional) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peri-implantitis, Peri-implant Mucositis, Hypersensitivity, Dental Implant Failure, Inflammatory Mediators