Antibacterial Photodynamic Therapy in the Management of Peri-implantitis

Peri-Implantitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06017817
• Other study ID #: HEALTHIER
• Status: Not yet recruiting
• Phase: N/A
• Start date: January 2, 2024
• Est. completion date: December 31, 2026

Study information

• Verified date: December 2023
• Source: Koite Health Oy
• Contact: Mikko Kylmänen
• Phone: +358407245934
• Email: mikko.kylmanen[@]koitehealth.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: December 31, 2026
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Dental Plaque
• Peri-Implantitis
• Plaque, Dental

Intervention

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
• Scaling and root planing (SRP
non-surgical anti-infective treatment by scaling and root planing
• surgical anti-infective peri-implantitis treatment
surgical anti-infective peri-implantitis treatment

Locations

Country	Name	City	State
Sweden	Södertandläkarna AB	Stockholm

Sponsors (2)

Lead Sponsor	Collaborator
Nilminie Rathnayake	University of Helsinki

Country where clinical trial is conducted

Sweden, 

References & Publications (8)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mobility assessment	Manual assessment of the template movement, mobility testing sideways, and up and down; - Scoring in numbers 0 - 3	6 months
Other	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
Primary	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	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
Secondary	Inflammatory marker total MMP-8 analysis	Measurement of pro and active MMP-8. Units: ng/ml.	6 months
Secondary	Inflammatory marker total MMP-9 analysis	Measurement of pro and active MMP-9. Units: ng/ml.	6 months
Secondary	Inflammatory marker total MMP-2 analysis	Measurement of pro and active MMP-2. Units: ng/ml.	6 months
Secondary	Inflammatory marker total TIMP analysis	Units: ng/ml.	6 months
Secondary	Interleukins analysis	Units: pg/ml.	6 months
Secondary	Total calprotectin analysis	Salivary calprotectin. Units: microgram/ml.	6 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Adverse events	Any suspicion of an adverse event related to the investigational device, the treatment method, or the study protocol.	6 months
Secondary	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

External 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
•   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
•   Pereira PAB, Aho VTE, Paulin L, et al., (2017) Oral and nasal microbiota in Parkinson's disease. Parkinsonism and Related Disorders 38: 61-67