Antibacterial Photodynamic Therapy in the Management of Peri-implantitis

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

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.

Study Overview

• Status: Recruiting
• Conditions: Peri-Implantitis; Plaque, Dental
• Intervention / Treatment: Device: Lumoral Treatment; Procedure: Standard oral hygiene instructions; Procedure: Scaling and root planing (SRP; Procedure: surgical anti-infective peri-implantitis treatment

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mikko Kylmänen; Phone Number: +358407245934; Email: mikko.kylmanen@koitehealth.com

Study Locations

• Sweden
  • Stockholm, Sweden, 11622
    • Recruiting
    • Södertandläkarna AB
    • Contact: Nilminie Rathnayake, Periodontist

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mobility assessment	Manual assessment of the template movement, mobility testing sideways, and up and down - Scoring in numbers 0 - 3	6 months
Suppuration index	- Visual assessment of the amount of pus, scoring: 0: No suppuration or exudate present; Minimal suppuration or exudate present; Moderate suppuration or exudate present; Severe suppuration or exudate present	6 months

Collaborators and Investigators

• Sponsor: Nilminie Rathnayake
• Collaborators: University of Helsinki
• Investigators: Principal Investigator: Nilminie Rathnayake, Assoc Prof, University of Helsinki

Publications and helpful links

General Publications

• Slade GD. Derivation and validation of a short-form oral health impact profile. Community Dent Oral Epidemiol. 1997 Aug;25(4):284-90. doi: 10.1111/j.1600-0528.1997.tb00941.x.
• Kassebaum NJ, Smith AGC, Bernabe E, Fleming TD, Reynolds AE, Vos T, Murray CJL, Marcenes W; GBD 2015 Oral Health Collaborators. Global, Regional, and National Prevalence, Incidence, and Disability-Adjusted Life Years for Oral Conditions for 195 Countries, 1990-2015: A Systematic Analysis for the Global Burden of Diseases, Injuries, and Risk Factors. J Dent Res. 2017 Apr;96(4):380-387. doi: 10.1177/0022034517693566.
• Kassebaum NJ, Bernabe E, Dahiya M, Bhandari B, Murray CJ, Marcenes W. Global burden of severe periodontitis in 1990-2010: a systematic review and meta-regression. J Dent Res. 2014 Nov;93(11):1045-53. doi: 10.1177/0022034514552491. Epub 2014 Sep 26.
• Lang NP, Suvan JE, Tonetti MS. Risk factor assessment tools for the prevention of periodontitis progression a systematic review. J Clin Periodontol. 2015 Apr;42 Suppl 16:S59-70. doi: 10.1111/jcpe.12350.
• Nikinmaa S, Moilanen N, Sorsa T, Rantala J, Alapulli H, Kotiranta A, Auvinen P, Kankuri E, Meurman JH, Patila T. Indocyanine Green-Assisted and LED-Light-Activated Antibacterial Photodynamic Therapy Reduces Dental Plaque. Dent J (Basel). 2021 May 3;9(5):52. doi: 10.3390/dj9050052.
• Lahteenmaki H, Patila T, Raisanen IT, Kankuri E, Tervahartiala T, Sorsa T. Repeated Home-Applied Dual-Light Antibacterial Photodynamic Therapy Can Reduce Plaque Burden, Inflammation, and aMMP-8 in Peri-Implant Disease-A Pilot Study. Curr Issues Mol Biol. 2022 Mar 8;44(3):1273-1283. doi: 10.3390/cimb44030085.
• Berglundh T, Jepsen S, Stadlinger B, Terheyden H. Peri-implantitis and its prevention. Clin Oral Implants Res. 2019 Feb;30(2):150-155. doi: 10.1111/clr.13401. Epub 2019 Feb 3.
• Jepsen S, Berglundh T, Genco R, Aass AM, Demirel K, Derks J, Figuero E, Giovannoli JL, Goldstein M, Lambert F, Ortiz-Vigon A, Polyzois I, Salvi GE, Schwarz F, Serino G, Tomasi C, Zitzmann NU. Primary prevention of peri-implantitis: managing peri-implant mucositis. J Clin Periodontol. 2015 Apr;42 Suppl 16:S152-7. doi: 10.1111/jcpe.12369.

Helpful Links

• Alaijah, F., Morsi, A., Nasher, R. et al. Photobiomodulation therapy in the treatment of periodontal disease: a literature review. Laser Dent Sci 3, 147-153 (2019)
• Gomes SC, Romagna R, Rossi V, Corvello PC, Melchiors-Angst PD. Supragingival treatment as an aid to reduce subgingival needs: a 450-day investigation Braz. oral res. 28 (1) 2014
• Pereira PAB, Aho VTE, Paulin L, et al., (2017) Oral and nasal microbiota in Parkinson's disease. Parkinsonism and Related Disorders 38: 61-67
• Levine JI. Medications that increase photosensitivity. FDA document Dec 1990.
• Nikinmaa S, Alapulli H, Auvinen P, et al. (2020) Dual-light photodynamic therapy administered daily provides a sustained antibacterial effect on biofilm and prevents Streptococcus mutans adaptation. PLoS ONE 15(5)
• Nikinmaa S, Podonyi A, Raivio P, et al. (2021). Daily Administered Dual-Light Photodynamic Therapy Provides a Sustained Antibacterial Effect on Staphylococcus aureus. Antibiotics, 10 (10): 1240

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2024
• Primary Completion (Estimated): March 31, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: August 24, 2023
• First Submitted That Met QC Criteria: August 24, 2023
• First Posted (Actual): August 30, 2023

Study Record Updates

• Last Update Posted (Actual): October 18, 2024
• Last Update Submitted That Met QC Criteria: October 16, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Plaque control; Lumoral; Lumorinse; aMMP-8; Antibacterial photodynamic therapy (aBPT)
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Periodontal Diseases; Mouth Diseases; Tooth Diseases; Dental Deposits; Peri-Implantitis; Dental Plaque; Anti-Infective Agents
• Other Study ID Numbers: HEALTHIER

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