Clinical and Microbiologic Outcomes of aPDT in the Non-surgical Treatment of Implant Inflammation

Study Overview
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Brief Summary
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The purpose of this study is to compare clinical outcomes (change in bleeding sites (BOP) and probing depth reduction (PPD) after mechanical debridement of implant surfaces at sites exhibiting plaque induced inflammation with or without adjunctive antimicrobial photodynamic therapy (aPDT) and assess the microbiologic profile of plaque samples before and after treatment with or without aPDT samples.

Official Title
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Clinical and Microbiologic Outcomes of Adjunctive Antimicrobial Photodynamic Therapy in the Non-surgical Treatment of Peri-implant Disease

Conditions
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DENT IMPLANTS, LASER

Intervention / Treatment
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* Procedure: Conventional mechanical therapy
* Drug: Saline
* Drug: Methylene Blue
* Device: Light emitting laser
* Device: Non-light emitting laser


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: at least one implant with peri-implant inflammation that requires non-surgical treatment. Peri-implant diseases included are peri-implant mucositis and peri-implantitis Criteria for diagnosis of peri-implant mucositis or peri-implantitis: Red, swollen gingival tissues surrounding the implant Presence of bleeding and/or suppuration on gentle probing around the implant Increased probing depth compared to probing depth after restoration of the implant (greater than 2mm increase in probing depth) May or may not have progressive bone loss in relation to radiographic bone levels assessed either 1 year following restoration of the implant OR ≥3mm of radiographic bone loss from the implant platform -systemically healthy or with controlled common systemic conditions, such as hypertension, that will not affect wound healing. Exclusion Criteria: current heavy smokers (>10 cigarettes/day) have diabetes or other systemic diseases that may comprise healing take antibiotics within 3 months before the procedure

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Conventional mechanical therapy with aPDT adjunct<br>Traditional non-surgical mechanical debridement along with antimicrobial photodynamic therapy will be done at implant sites by applying a photosensitizing dye methylene blue (0.1mg/ml) with a disposable syringe from the bottom of pocket in a coronal direction. The dye will be applied topically confined to the epithelialized space surrounding the implant fixture and will not be internalized. After 5 minutes in situ, the surrounding gingival tissues will be irradiated at six sites around the implant using a diode laser with a wavelength of 660nm, providing an energy density of 10 J/site, 100mW power, time equal to 100 seconds. After irradiation, the site will be thoroughly rinsed with saline. | Procedure: Conventional mechanical therapy<br>* Both experimental and sham arms will receive the Conventional mechanical therapy<br>Drug: Methylene Blue<br>* Experimental arm will receive methylene blue<br>Device: Light emitting laser<br>* Experimental arm will receive Light emitting laser<br>|
| Sham Comparator: Conventional mechanical therapy with sham aPDT treatment<br>Control group will have conventional mechanical instrumentation of implant site with Sham aPDT treatment with saline and non-light emitting laser | Procedure: Conventional mechanical therapy<br>* Both experimental and sham arms will receive the Conventional mechanical therapy<br>Drug: Saline<br>* Sham group will receive saline as a sham for methylene blue<br>Device: Non-light emitting laser<br>* Sham group will receive Non-light emitting laser<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Probing Pocket Depth | Periodontal pocket depth was measured from the free gingival margin to the base of the pocket, with a UNC periodontal probe with 1mm measurement units. It was assessed at 6 sites per implant: mesiobuccal, mid-buccal, distobuccal, distolingual, mid-lingual, and mesiolingual. For each participant, an average of the depths of the 6 sites is reported. | Baseline | 
| Mean Probing Pocket Depth | Periodontal pocket depth was measured from the free gingival margin to the base of the pocket, with a UNC periodontal probe with 1mm measurement units. It was assessed at 6 sites per implant: mesiobuccal, mid-buccal, distobuccal, distolingual, mid-lingual, and mesiolingual. For each participant, an average of the depths of the 6 sites is reported. | 6 weeks post treatment | 
| Mean Probing Pocket Depth | Periodontal pocket depth was measured from the free gingival margin to the base of the pocket, with a UNC periodontal probe with 1mm measurement units. It was assessed at 6 sites per implant: mesiobuccal, mid-buccal, distobuccal, distolingual, mid-lingual, and mesiolingual. For each participant, an average of the depths of the 6 sites is reported. | 12 weeks post treatment | 
| Improvement in Sites as Indicated by Reduction in Inflammation as Assessed by Clinical Attachment Loss |  | Baseline | 
| Improvement in Sites as Indicated by Reduction in Inflammation as Assessed by Clinical Attachment Loss |  | 6 weeks post treatment | 
| Improvement in Sites as Indicated by Reduction in Inflammation as Assessed by Clinical Attachment Loss |  | 12 weeks post treatment | 
| Number of Bleeding Sites Per Participant as Assessed by Bleeding on Probing | Bleeding on probing (BOP) will be assessed, where each of 6 gingival areas (mesiobuccal, mid-buccal, distobuccal, distolingual, mid-lingual, and mesiolingual) around each tooth will be gently swept by the periodontal probe just within the gingival sulcus of the implant and the presence or absence of bleeding will be recorded. | Baseline | 
| Number of Bleeding Sites Per Participant as Assessed by Bleeding on Probing | Bleeding on probing (BOP) will be assessed, where each of 6 gingival areas (mesiobuccal, mid-buccal, distobuccal, distolingual, mid-lingual, and mesiolingual) around each tooth will be gently swept by the periodontal probe just within the gingival sulcus of the implant and the presence or absence of bleeding will be recorded. | 6 weeks post treatment | 
| Number of Bleeding Sites Per Participant as Assessed by Bleeding on Probing | Bleeding on probing (BOP) will be assessed, where each of 6 gingival areas (mesiobuccal, mid-buccal, distobuccal, distolingual, mid-lingual, and mesiolingual) around each tooth will be gently swept by the periodontal probe just within the gingival sulcus of the implant and the presence or absence of bleeding will be recorded. | 12 weeks post treatment | 
| Number of Sites With Plaque Per Participant | Presence of plaque was evaluated at six sites (mesiobuccal, mid-buccal, distobuccal, distolingual, mid-lingual, and mesiolingual) around the implant surface and the presence of plaque will be recorded. | Baseline | 
| Number of Sites With Plaque Per Participant | Presence of plaque was evaluated at six sites (mesiobuccal, mid-buccal, distobuccal, distolingual, mid-lingual, and mesiolingual) around the implant surface and the presence of plaque will be recorded. | 6 weeks post treatment | 
| Number of Sites With Plaque Per Participant | Presence of plaque was evaluated at six sites (mesiobuccal, mid-buccal, distobuccal, distolingual, mid-lingual, and mesiolingual) around the implant surface and the presence of plaque will be recorded. | 12 weeks post treatment | 
| Max Probing Pocket Depth | Periodontal pocket depth was measured from the free gingival margin to the base of the pocket, with a UNC periodontal probe with 1mm measurement units. It was assessed at 6 sites per implant: mesiobuccal, mid-buccal, distobuccal, distolingual, mid-lingual, and mesiolingual. For each participant, the depth of the deepest of the 6 sites is reported. | Baseline | 
| Max Probing Pocket Depth | Periodontal pocket depth was measured from the free gingival margin to the base of the pocket, with a UNC periodontal probe with 1mm measurement units. It was assessed at 6 sites per implant: mesiobuccal, mid-buccal, distobuccal, distolingual, mid-lingual, and mesiolingual. For each participant, the depth of the deepest of the 6 sites is reported. | 6 weeks post treatment | 
| Max Probing Pocket Depth | Periodontal pocket depth was measured from the free gingival margin to the base of the pocket, with a UNC periodontal probe with 1mm measurement units. It was assessed at 6 sites per implant: mesiobuccal, mid-buccal, distobuccal, distolingual, mid-lingual, and mesiolingual. For each participant, the depth of the deepest of the 6 sites is reported. | 12 weeks post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of 16S rRNA Gene Data From Plaque Samples | Plaque samples will be taken from the deepest probing site of each implant at baseline and 12 weeks after aPDT. Bacterial analysis through 16S rRNA gene V4 amplification and sequencing. 16S rRNA gene data will then be analyzed assessing for a change in microbiota community associated with a healthy implant site. | Baseline | 
| Assessment of 16S rRNA Gene Data From Plaque Samples | Plaque samples will be taken from the deepest probing site of each implant at baseline and 12 weeks after aPDT. Bacterial analysis through 16S rRNA gene V4 amplification and sequencing. 16S rRNA gene data will then be analyzed assessing for a change in microbiota community associated with a healthy implant site. | 12 weeks post treatment | 
| Levels of Immunologic Biomarkers in Peri-implant Sulcular Fluid (PISF) Sample as Assessed by Multiplexed Fluorescent Bead-based Immunoassay | PISF samples will be taken from six sites of each implant at baseline and 12 weeks after aPDT. The levels of interleukin IL-1a, IL-1b, IL-6, IL-8, IL-10, IL-12, IL-7A, tumor necrosis factor (TNF)-a, C-reactive protein, osteoprotegerin, leptin, and adiponectin will be determined using multiplex proteomic immunoassays. | Baseline | 
| Levels of Immunologic Biomarkers in Peri-implant Sulcular Fluid (PISF) Sample as Assessed by Multiplexed Fluorescent Bead-based Immunoassay | PISF samples will be taken from six sites of each implant at baseline and 12 weeks after aPDT. The levels of interleukin IL-1a, IL-1b, IL-6, IL-8, IL-10, IL-12, IL-7A, tumor necrosis factor (TNF)-a, C-reactive protein, osteoprotegerin, leptin, and adiponectin will be determined using multiplex proteomic immunoassays. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dental implants, Laser, Antimicrobial photodynamic therapy, Low level laser therapy, Peri-implant mucositis, Peri-implantitis