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

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

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.

Study Overview

• Status: Completed
• Conditions: LASER; DENT IMPLANTS
• Intervention / Treatment: Procedure: Conventional mechanical therapy; Drug: Methylene Blue; Device: Light emitting laser; Drug: Saline; Device: Non-light emitting laser

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jiayin Tan, DDS; Phone Number: 713-486-4048; Email: Jiayin.Tan@uth.tmc.edu
• Study Contact Backup: Name: Juliana A. Barros, DDS, MS; Phone Number: 713-486-4564; Email: Juliana.Barros@uth.tmc.edu

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center at Houston School of Dentistry

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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:

1. Red, swollen gingival tissues surrounding the implant
2. Presence of bleeding and/or suppuration on gentle probing around the implant
3. Increased probing depth compared to probing depth after restoration of the implant (greater than 2mm increase in probing depth)
4. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Conventional mechanical therapy with aPDT adjunct; 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; Both experimental and sham arms will receive the Conventional mechanical therapy; Drug: Methylene Blue; Experimental arm will receive methylene blue; Device: Light emitting laser; Experimental arm will receive Light emitting laser
Sham Comparator: Conventional mechanical therapy with sham aPDT treatment; 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; Both experimental and sham arms will receive the Conventional mechanical therapy; Drug: Saline; Sham group will receive saline as a sham for methylene blue; Device: Non-light emitting laser; Sham group will receive Non-light emitting laser

What is the study measuring?

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
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
Alpha Diversity as Indicated by Analysis 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. To assess bacteria in the sample, the V4 region of the 16S rRNA gene will be PCR amplified and sequenced, and 16S rRNA gene data will then be analyzed to determine the alpha diversity of the microbiota community at the implant site. In this study, the minimum alpha diversity is 1 and the maximum is 2501. A higher alpha diversity indicates a higher number of bacterial or taxonomic "units" in the sample.	Baseline
Alpha Diversity as Indicated by Analysis 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. To assess bacteria in the sample, the V4 region of the 16S rRNA gene will be PCR amplified and sequenced, and 16S rRNA gene data will then be analyzed to determine the alpha diversity of the microbiota community at the implant site. In this study, the minimum alpha diversity is 1 and the maximum is 2501. A higher alpha diversity indicates a higher number of bacterial or taxonomic "units" in the sample.	12 weeks post treatment

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Collaborators: Academy of Laser Dentistry (ALD)
• Investigators: Principal Investigator: Jiayin Tan, DDS, The University of Texas Health Science Center, Houston

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2020
• Primary Completion (Actual): December 6, 2022
• Study Completion (Actual): December 6, 2022

Study Registration Dates

• First Submitted: November 26, 2019
• First Submitted That Met QC Criteria: December 2, 2019
• First Posted (Actual): December 5, 2019

Study Record Updates

• Last Update Posted (Estimated): February 21, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Dental implants; Peri-implantitis; Laser; Low level laser therapy; Antimicrobial photodynamic therapy; Peri-implant mucositis
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Methylene Blue
• Other Study ID Numbers: HSC-DB-19-0873

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: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No