xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06017817</url>
    </required_header>
    <id_info>
      <org_study_id>HEALTHIER</org_study_id>
      <nct_id>NCT06017817</nct_id>
    </id_info>
    <brief_title>Antibacterial Photodynamic Therapy in the Management of Peri-implantitis</brief_title>
    <official_title>Regular Home-use of Antibacterial Photodynamic Therapy in the Management of Peri-implantitis</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Nilminie Rathnayake</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>University of Helsinki</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Koite Health Oy</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This early-stage study is designed to determine the efficacy of the Lumoral method in&#xD;
        periimplantitis. Improved supragingival plaque control can help to also sustain subgingival&#xD;
        plaque management in the long term. In addition, the device might have a photobiomodulation&#xD;
        effect on periodontal tissues, thus impacting osseointegration.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Clinical signs of inflammation in peri-implantitis include bleeding on probing, suppuration,&#xD;
        increased probing depth, and radiographic signs of bone loss. Currently, the best treatment&#xD;
        options for peri-implantitis include non-surgical methods of biofilm removal in the&#xD;
        supra-mucosal area around implants, and comprehensive guidance on self-performed infection&#xD;
        control procedures. With more advanced peri-implantitis, anti-infective surgical treatment&#xD;
        protocol would be needed.&#xD;
  &#xD;
        Matrix metalloproteinase 8 (MMP-8) has been found to be elevated in association with oral&#xD;
        infections, such as periodontitis and peri-implantitis. The level of active MMP-8 (aMMP-8)&#xD;
        can detect to determine tissue health and to assess inflammation, and can easily be measured&#xD;
        during a regular dental appointment with a chairside test.&#xD;
  &#xD;
        The Lumoral Treatment is a CE-marked medical device developed to provide a potent, targeted&#xD;
        antibacterial action on dental plaque in a home environment. The method mechanism of action&#xD;
        is antibacterial photodynamic therapy (aPDT). The method is used by swishing a mouth rinse,&#xD;
        which has a strong adherence to dental plaque. The plaque-adhered photoactive mouth rinse can&#xD;
        be activated by a simple-to-use light applicator. Preliminary results have shown a promising&#xD;
        anti-inflammatory response in addition to plaque reduction.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 1, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2026</completion_date>
    <primary_completion_date type="Anticipated">March 31, 2025</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_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).</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Double (Participant, Investigator)</masking>
      <masking_description>The first assessments will be made before randomization.&#xD;
  After the randomization, there is no masking.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Bleeding on probing (BOP)</measure>
      <time_frame>6 months</time_frame>
      <description>Change in the inflammatory parameter BOP. A full-mouth assessment at six sites per tooth:&#xD;
  Gingival bleeding is considered as positive if bleeding occurs within 15 seconds after gentle probing with a probe at the sulcus&#xD;
  Dichotomous scoring to each site of the tooth as bleeding &quot;1 present&quot; and &quot;0 absent&quot;&#xD;
  BOP reported as the percentage (%) of sites with positive findings&#xD;
  Calculation formula: number of bleeding sites/ 6 times number of teeth</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Active matrix metalloproteinase 8 (aMMP-8)</measure>
      <time_frame>6 months</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Inflammatory marker total MMP-8 analysis</measure>
      <time_frame>6 months</time_frame>
      <description>Measurement of pro and active MMP-8. Units: ng/ml.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Inflammatory marker total MMP-9 analysis</measure>
      <time_frame>6 months</time_frame>
      <description>Measurement of pro and active MMP-9. Units: ng/ml.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Inflammatory marker total MMP-2 analysis</measure>
      <time_frame>6 months</time_frame>
      <description>Measurement of pro and active MMP-2. Units: ng/ml.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Inflammatory marker total TIMP analysis</measure>
      <time_frame>6 months</time_frame>
      <description>Units: ng/ml.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Interleukins analysis</measure>
      <time_frame>6 months</time_frame>
      <description>Units: pg/ml.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Total calprotectin analysis</measure>
      <time_frame>6 months</time_frame>
      <description>Salivary calprotectin. Units: microgram/ml.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Peridontal Pocket Depth (PPD)</measure>
      <time_frame>6 months</time_frame>
      <description>A full-mouth assessment, measured at six sites per tooth. Assessed from the base of the pocket to the gingival margin (mm)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Visual Plaque Index( VPI)</measure>
      <time_frame>6 months</time_frame>
      <description>Assessment of six index teeth, measured at four sites per tooth&#xD;
  Dichotomous scoring to each site of the tooth as plaque &quot;1 present&quot; and &quot;0 absent&quot;&#xD;
  VPI reported as the percentage (%) of sites with plaque&#xD;
  Calculation formula: number of sites with plaque/ 4 times number of teeth</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Clinical Attachment Level (CAL)</measure>
      <time_frame>6 months</time_frame>
      <description>A full-mouth assessment, measured at six sites per tooth&#xD;
  - Assessed as the distance from the cementoenamel junction (CEJ) to the bottom of the periodontal pocket (mm)&#xD;
  The measurements to calculate CAL:&#xD;
  distance from the gingival margin to the CEJ and PPD&#xD;
  in recession: PPD + gingival margin to the CEJ&#xD;
  in tissue overgrowth: PPD - gingival margin to the CEJ</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Bacterial flora</measure>
      <time_frame>6 Months</time_frame>
      <description>Quantification of periodontopathic bacteria by 16S rRNA sequencing analysis&#xD;
  - 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</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Adverse events</measure>
      <time_frame>6 months</time_frame>
      <description>Any suspicion of an adverse event related to the investigational device, the treatment method, or the study protocol.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>OHIP-14 questionnaire</measure>
      <time_frame>6 months</time_frame>
      <description>- Measures people's perception of the social impact of oral disorders on their well-being.&#xD;
  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).</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Mobility assessment</measure>
      <time_frame>6 months</time_frame>
      <description>Manual assessment of the template movement, mobility testing sideways, and up and down&#xD;
  - Scoring in numbers 0 - 3</description>
    </other_outcome>
    <other_outcome>
      <measure>Suppuration index</measure>
      <time_frame>6 months</time_frame>
      <description>- Visual assessment of the amount of pus, scoring: 0: No suppuration or exudate present&#xD;
  Minimal suppuration or exudate present&#xD;
  Moderate suppuration or exudate present&#xD;
  Severe suppuration or exudate present</description>
    </other_outcome>
    <number_of_arms>4</number_of_arms>
    <enrollment type="Anticipated">80</enrollment>
    <condition>Peri-Implantitis</condition>
    <condition>Plaque, Dental</condition>
    <arm_group>
      <arm_group_label>Non-surgical treatment, Study group (NST-1)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>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.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Non-surgical treatment, Control group (NST-2)</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>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.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Surgical treatment, Study group (ST-1)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Lumoral Treatment; Surgical anti-infective peri-implantitis treatment; and Standard oral hygiene instructions for electric toothbrushing, interdental brush, and dental floss use.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Surgical treatment, Control group (ST-2)</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Surgical anti-infective peri-implantitis treatment; and Standard oral hygiene instructions for electric toothbrushing, interdental brush, and dental floss use.</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Lumoral Treatment</intervention_name>
      <description>Anti-infective photodynamic therapy for plaque-induced oral conditions</description>
      <arm_group_label>Non-surgical treatment, Study group (NST-1)</arm_group_label>
      <arm_group_label>Surgical treatment, Study group (ST-1)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Standard oral hygiene instructions</intervention_name>
      <description>Standard oral hygiene instructions for electric toothbrushing, interdental brush, and dental floss use</description>
      <arm_group_label>Non-surgical treatment, Control group (NST-2)</arm_group_label>
      <arm_group_label>Non-surgical treatment, Study group (NST-1)</arm_group_label>
      <arm_group_label>Surgical treatment, Control group (ST-2)</arm_group_label>
      <arm_group_label>Surgical treatment, Study group (ST-1)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Scaling and root planing (SRP</intervention_name>
      <description>non-surgical anti-infective treatment by scaling and root planing</description>
      <arm_group_label>Non-surgical treatment, Control group (NST-2)</arm_group_label>
      <arm_group_label>Non-surgical treatment, Study group (NST-1)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>surgical anti-infective peri-implantitis treatment</intervention_name>
      <description>surgical anti-infective peri-implantitis treatment</description>
      <arm_group_label>Surgical treatment, Control group (ST-2)</arm_group_label>
      <arm_group_label>Surgical treatment, Study group (ST-1)</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  PPD ≥6 mm and marginal bone loss &gt;3 mm&#xD;
  &#xD;
            -  Dental implants collected and clinically characterized according to Lähteenmäki et al.&#xD;
               CEDR-22&#xD;
  &#xD;
            -  Agreement to participate in the study and to sign a written consent form&#xD;
  &#xD;
            -  Able to co-operate with the treatment protocol and avoid any other oral hygiene&#xD;
               measures outside of the study protocol&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Presence of any physical limitation or restriction that might restrict Lumoral use&#xD;
  &#xD;
            -  Unwilling to participate in the study&#xD;
  &#xD;
            -  Pregnancy or lactation&#xD;
  &#xD;
            -  Active smoking&#xD;
  &#xD;
            -  Medicated diabetes mellitus (DM)&#xD;
  &#xD;
            -  Any systemic disease (e.g., wound healing dysfunctions) that could alter the&#xD;
               progression of peri-implantitis&#xD;
  &#xD;
            -  Use of antibiotics and doxycycline, chlorhexidine, and bisphosphonates, within 4 weeks&#xD;
               week prior to study participation&#xD;
  &#xD;
            -  Peri-implant and periodontal treatment within 3 months prior to study participation&#xD;
  &#xD;
            -  Removable major prosthesis or major orthodontic appliance&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>85 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Nilminie Rathnayake, Assoc Prof</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Helsinki</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Mikko Kylmänen</last_name>
      <phone>+358407245934</phone>
      <email>mikko.kylmanen@koitehealth.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Södertandläkarna AB</name>
        <address>
          <city>Stockholm</city>
          <zip>11622</zip>
          <country>Sweden</country>
        </address>
      </facility>
      <contact>
        <last_name>Nilminie Rathnayake, Periodontist</last_name>
      </contact>
    </location>
    <location_countries>
      <country>Sweden</country>
    </location_countries>
    <link>
      <url>https://doi.org/10.1007/s41547-019-00056-9</url>
      <description>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)</description>
    </link>
    <link>
      <url>https://doi.org/10.1590/S1806-83242014.50000004</url>
      <description>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</description>
    </link>
    <link>
      <url>https://www.fda.gov/media/75892/download</url>
      <description>Levine JI. Medications that increase photosensitivity. FDA document Dec 1990.</description>
    </link>
    <link>
      <url>https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232775</url>
      <description>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)</description>
    </link>
    <link>
      <url>https://doi.org/10.3390/antibiotics10101240</url>
      <description>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</description>
    </link>
    <link>
      <url>https://doi.org/10.1016/j.parkreldis.2017.02.026</url>
      <description>Pereira PAB, Aho VTE, Paulin L, et al., (2017) Oral and nasal microbiota in Parkinson's disease. Parkinsonism and Related Disorders 38: 61-67</description>
    </link>
    <reference>
      <citation>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.</citation>
      <PMID>30636066</PMID>
    </reference>
    <reference>
      <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.</citation>
      <PMID>25626479</PMID>
    </reference>
    <reference>
      <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.</citation>
      <PMID>25261053</PMID>
    </reference>
    <reference>
      <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.</citation>
      <PMID>28792274</PMID>
    </reference>
    <reference>
      <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.</citation>
      <PMID>25496279</PMID>
    </reference>
    <reference>
      <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.</citation>
      <PMID>35723308</PMID>
    </reference>
    <reference>
      <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.</citation>
      <PMID>34063662</PMID>
    </reference>
    <reference>
      <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.</citation>
      <PMID>9332805</PMID>
    </reference>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 24, 2023</study_first_submitted>
    <study_first_submitted_qc>August 24, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 30, 2023</study_first_posted>
    <last_update_submitted>September 5, 2023</last_update_submitted>
    <last_update_submitted_qc>September 5, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 7, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>Koite Health Oy</investigator_affiliation>
      <investigator_full_name>Nilminie Rathnayake</investigator_full_name>
      <investigator_title>Principal Investigator</investigator_title>
    </responsible_party>
    <keyword>Lumoral</keyword>
    <keyword>Lumorinse</keyword>
    <keyword>Antibacterial photodynamic therapy (aBPT)</keyword>
    <keyword>aMMP-8</keyword>
    <keyword>Plaque control</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Peri-Implantitis</mesh_term>
      <mesh_term>Dental Plaque</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Anti-Infective Agents</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06017817
  org study id: HEALTHIER
  nct id: NCT06017817
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  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.
  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.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention 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).
  primary purpose: Treatment
  masking: Double (Participant, Investigator)
  masking description: The first assessments will be made before randomization.
  After the randomization, there is no masking.
  measure: Bleeding on probing (BOP)
  time frame: 6 months
  description: 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
  measure: Active matrix metalloproteinase 8 (aMMP-8)
  time frame: 6 months
  description: 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.
  measure: Inflammatory marker total MMP-8 analysis
  time frame: 6 months
  description: Measurement of pro and active MMP-8. Units: ng/ml.
  measure: Inflammatory marker total MMP-9 analysis
  time frame: 6 months
  description: Measurement of pro and active MMP-9. Units: ng/ml.
  measure: Inflammatory marker total MMP-2 analysis
  time frame: 6 months
  description: Measurement of pro and active MMP-2. Units: ng/ml.
  measure: Inflammatory marker total TIMP analysis
  time frame: 6 months
  description: Units: ng/ml.
  measure: Interleukins analysis
  time frame: 6 months
  description: Units: pg/ml.
  measure: Total calprotectin analysis
  time frame: 6 months
  description: Salivary calprotectin. Units: microgram/ml.
  measure: Peridontal Pocket Depth (PPD)
  time frame: 6 months
  description: A full-mouth assessment, measured at six sites per tooth. Assessed from the base of the pocket to the gingival margin (mm)
  measure: Visual Plaque Index( VPI)
  time frame: 6 months
  description: 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
  measure: Clinical Attachment Level (CAL)
  time frame: 6 months
  description: 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
  measure: Bacterial flora
  time frame: 6 Months
  description: 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
  measure: Adverse events
  time frame: 6 months
  description: Any suspicion of an adverse event related to the investigational device, the treatment method, or the study protocol.
  measure: OHIP-14 questionnaire
  time frame: 6 months
  description: - 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).
  measure: Mobility assessment
  time frame: 6 months
  description: Manual assessment of the template movement, mobility testing sideways, and up and down
  - Scoring in numbers 0 - 3
  measure: Suppuration index
  time frame: 6 months
  description: - 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
  arm group label: Non-surgical treatment, Study group (NST-1)
  arm group type: Experimental
  description: 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.
  arm group label: Non-surgical treatment, Control group (NST-2)
  arm group type: Active Comparator
  description: 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.
  arm group label: Surgical treatment, Study group (ST-1)
  arm group type: Experimental
  description: Lumoral Treatment; Surgical anti-infective peri-implantitis treatment; and Standard oral hygiene instructions for electric toothbrushing, interdental brush, and dental floss use.
  arm group label: Surgical treatment, Control group (ST-2)
  arm group type: Active Comparator
  description: Surgical anti-infective peri-implantitis treatment; and Standard oral hygiene instructions for electric toothbrushing, interdental brush, and dental floss use.
  intervention type: Device
  intervention name: Lumoral Treatment
  description: Anti-infective photodynamic therapy for plaque-induced oral conditions
  arm group label: Non-surgical treatment, Study group (NST-1)
  arm group label: Surgical treatment, Study group (ST-1)
  intervention type: Procedure
  intervention name: Standard oral hygiene instructions
  description: Standard oral hygiene instructions for electric toothbrushing, interdental brush, and dental floss use
  arm group label: Non-surgical treatment, Control group (NST-2)
  arm group label: Non-surgical treatment, Study group (NST-1)
  arm group label: Surgical treatment, Control group (ST-2)
  arm group label: Surgical treatment, Study group (ST-1)
  intervention type: Procedure
  intervention name: Scaling and root planing (SRP
  description: non-surgical anti-infective treatment by scaling and root planing
  arm group label: Non-surgical treatment, Control group (NST-2)
  arm group label: Non-surgical treatment, Study group (NST-1)
  intervention type: Procedure
  intervention name: surgical anti-infective peri-implantitis treatment
  description: surgical anti-infective peri-implantitis treatment
  arm group label: Surgical treatment, Control group (ST-2)
  arm group label: Surgical treatment, Study group (ST-1)
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 85 Years
  healthy volunteers: No
  last name: Nilminie Rathnayake, Assoc Prof
  role: Principal Investigator
  affiliation: University of Helsinki
  last name: Mikko Kylmänen
  phone: +358407245934
  email: mikko.kylmanen@koitehealth.com
  facility: 
  contact: 
  country: Sweden
  url: https://doi.org/10.1007/s41547-019-00056-9
  description: 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)
  url: https://doi.org/10.1590/S1806-83242014.50000004
  description: 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
  url: https://www.fda.gov/media/75892/download
  description: Levine JI. Medications that increase photosensitivity. FDA document Dec 1990.
  url: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232775
  description: 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)
  url: https://doi.org/10.3390/antibiotics10101240
  description: 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
  url: https://doi.org/10.1016/j.parkreldis.2017.02.026
  description: Pereira PAB, Aho VTE, Paulin L, et al., (2017) Oral and nasal microbiota in Parkinson's disease. Parkinsonism and Related Disorders 38: 61-67
  citation: 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.
  PMID: 30636066
  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.
  PMID: 25626479
  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.
  PMID: 25261053
  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.
  PMID: 28792274
  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.
  PMID: 25496279
  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.
  PMID: 35723308
  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.
  PMID: 34063662
  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.
  PMID: 9332805
  responsible party type: Sponsor-Investigator
  investigator affiliation: Koite Health Oy
  investigator full name: Nilminie Rathnayake
  investigator title: Principal Investigator
  mesh term: Peri-Implantitis
  mesh term: Dental Plaque
  mesh term: Anti-Infective Agents
  sharing ipd: No