Antibacterial Photodynamic Therapy in the Management of Peri-implantitis

Study Overview
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Brief Summary
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This early-stage study is designed to determine the efficacy of the Lumoral method in periimplantitis. Improved supragingival plaque control can help to also sustain subgingival plaque management in the long term. In addition, the device might have a photobiomodulation effect on periodontal tissues, thus impacting osseointegration.

Detailed Description
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Clinical signs of inflammation in peri-implantitis include bleeding on probing, suppuration, increased probing depth, and radiographic signs of bone loss. Currently, the best treatment options for peri-implantitis include non-surgical methods of biofilm removal in the supra-mucosal area around implants, and comprehensive guidance on self-performed infection control procedures. With more advanced peri-implantitis, anti-infective surgical treatment protocol would be needed. Matrix metalloproteinase 8 (MMP-8) has been found to be elevated in association with oral infections, such as periodontitis and peri-implantitis. The level of active MMP-8 (aMMP-8) can detect to determine tissue health and to assess inflammation, and can easily be measured during a regular dental appointment with a chairside test. The Lumoral Treatment is a CE-marked medical device developed to provide a potent, targeted antibacterial action on dental plaque in a home environment. The method mechanism of action is antibacterial photodynamic therapy (aPDT). The method is used by swishing a mouth rinse, which has a strong adherence to dental plaque. The plaque-adhered photoactive mouth rinse can be activated by a simple-to-use light applicator. Preliminary results have shown a promising anti-inflammatory response in addition to plaque reduction.

Official Title
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Regular Home-use of Antibacterial Photodynamic Therapy in the Management of Peri-implantitis

Conditions
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Peri-Implantitis, Plaque, Dental

Intervention / Treatment
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* Device: Lumoral Treatment
* Procedure: Standard oral hygiene instructions
* Procedure: Scaling and root planing (SRP
* Procedure: surgical anti-infective peri-implantitis treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: PPD ≥6 mm and marginal bone loss >3 mm Dental implants collected and clinically characterized according to Lähteenmäki et al. CEDR-22 Agreement to participate in the study and to sign a written consent form Able to co-operate with the treatment protocol and avoid any other oral hygiene measures outside of the study protocol Exclusion Criteria: Presence of any physical limitation or restriction that might restrict Lumoral use Unwilling to participate in the study Pregnancy or lactation Active smoking Medicated diabetes mellitus (DM) Any systemic disease (e.g., wound healing dysfunctions) that could alter the progression of peri-implantitis Use of antibiotics and doxycycline, chlorhexidine, and bisphosphonates, within 4 weeks week prior to study participation Peri-implant and periodontal treatment within 3 months prior to study participation Removable major prosthesis or major orthodontic appliance

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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
Interventional Model Description: 80 subjects in total are recruited to this study: 40 subjects in the non-surgical treatment (NST), of which 20 participants in the NST Study group (NST-1) and 20 participants in the NST Control group (NST-2), and 40 subjects in the surgical treatment (ST), of which 20 participants in the ST Study group (ST-1) and 20 participants in the ST Control group (ST-2).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Non-surgical treatment, Study group (NST-1)<br>Lumoral Treatment; Standard, non-surgical anti-infective treatment by scaling and root planing (SRP); and Standard oral hygiene instructions for electric toothbrushing, interdental brush, and dental floss use. | Device: Lumoral Treatment<br>* Anti-infective photodynamic therapy for plaque-induced oral conditions<br>Procedure: Standard oral hygiene instructions<br>* Standard oral hygiene instructions for electric toothbrushing, interdental brush, and dental floss use<br>Procedure: Scaling and root planing (SRP<br>* non-surgical anti-infective treatment by scaling and root planing<br>|
| Active Comparator: Non-surgical treatment, Control group (NST-2)<br>Standard, non-surgical anti-infective treatment by scaling and root planing (SRP); and Standard oral hygiene instructions for electric toothbrushing, interdental brush, and dental floss use. | Procedure: Standard oral hygiene instructions<br>* Standard oral hygiene instructions for electric toothbrushing, interdental brush, and dental floss use<br>Procedure: Scaling and root planing (SRP<br>* non-surgical anti-infective treatment by scaling and root planing<br>|
| Experimental: Surgical treatment, Study group (ST-1)<br>Lumoral Treatment; Surgical anti-infective peri-implantitis treatment; and Standard oral hygiene instructions for electric toothbrushing, interdental brush, and dental floss use. | Device: Lumoral Treatment<br>* Anti-infective photodynamic therapy for plaque-induced oral conditions<br>Procedure: Standard oral hygiene instructions<br>* Standard oral hygiene instructions for electric toothbrushing, interdental brush, and dental floss use<br>Procedure: surgical anti-infective peri-implantitis treatment<br>* surgical anti-infective peri-implantitis treatment<br>|
| Active Comparator: Surgical treatment, Control group (ST-2)<br>Surgical anti-infective peri-implantitis treatment; and Standard oral hygiene instructions for electric toothbrushing, interdental brush, and dental floss use. | Procedure: Standard oral hygiene instructions<br>* Standard oral hygiene instructions for electric toothbrushing, interdental brush, and dental floss use<br>Procedure: surgical anti-infective peri-implantitis treatment<br>* surgical anti-infective peri-implantitis treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding on probing (BOP) | Change in the inflammatory parameter BOP. A full-mouth assessment at six sites per tooth: Gingival bleeding is considered as positive if bleeding occurs within 15 seconds after gentle probing with a probe at the sulcus Dichotomous scoring to each site of the tooth as bleeding 1 present and 0 absent BOP reported as the percentage (%) of sites with positive findings Calculation formula: number of bleeding sites/ 6 times number of teeth | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Active matrix metalloproteinase 8 (aMMP-8) | The oral rinse fluid sample collection and the aMMP-8 marker analysis will be performed using Periosafe test (Dentognostics GmbH) according to the manufacturer's instructions. | 6 months | 
| Inflammatory marker total MMP-8 analysis | Measurement of pro and active MMP-8. Units: ng/ml. | 6 months | 
| Inflammatory marker total MMP-9 analysis | Measurement of pro and active MMP-9. Units: ng/ml. | 6 months | 
| Inflammatory marker total MMP-2 analysis | Measurement of pro and active MMP-2. Units: ng/ml. | 6 months | 
| Inflammatory marker total TIMP analysis | Units: ng/ml. | 6 months | 
| Interleukins analysis | Units: pg/ml. | 6 months | 
| Total calprotectin analysis | Salivary calprotectin. Units: microgram/ml. | 6 months | 
| Peridontal Pocket Depth (PPD) | A full-mouth assessment, measured at six sites per tooth. Assessed from the base of the pocket to the gingival margin (mm) | 6 months | 
| Visual Plaque Index( VPI) | Assessment of six index teeth, measured at four sites per tooth Dichotomous scoring to each site of the tooth as plaque 1 present and 0 absent VPI reported as the percentage (%) of sites with plaque Calculation formula: number of sites with plaque/ 4 times number of teeth | 6 months | 
| Clinical Attachment Level (CAL) | A full-mouth assessment, measured at six sites per tooth - Assessed as the distance from the cementoenamel junction (CEJ) to the bottom of the periodontal pocket (mm) The measurements to calculate CAL: distance from the gingival margin to the CEJ and PPD in recession: PPD + gingival margin to the CEJ in tissue overgrowth: PPD - gingival margin to the CEJ | 6 months | 
| Bacterial flora | Quantification of periodontopathic bacteria by 16S rRNA sequencing analysis - Microbiological samples can be collected using Iso Taper Paper Points, size-20 (VDW GmbH) from selected gingival/periodontal pockets with maximum initial probing depth. The paper points can be placed into sterile, small-aliquot containers, and immediately stored at -20°C until analysis | 6 Months | 
| Adverse events | Any suspicion of an adverse event related to the investigational device, the treatment method, or the study protocol. | 6 months | 
| OHIP-14 questionnaire | - Measures people's perception of the social impact of oral disorders on their well-being. Fourteen items of OHIP are divided into seven dimensions: functional limitation, physical discomfort, psychological discomfort, physical disability, psychological disability, social disability, and handicaps. (Slade GD 1997). Responses are made on a 5-point scale (from 0 = never, to 4 = very often). | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aMMP-8, Lumoral, Lumorinse, Antibacterial photodynamic therapy (aBPT), Plaque control