<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/NCT03757260</url>
  </required_header>
  <id_info>
    <org_study_id>B2018:012</org_study_id>
    <nct_id>NCT03757260</nct_id>
  </id_info>
  <brief_title>Efficacy of Adjunctive Antimicrobial Photodynamic Therapy for Residual Pockets in Previously Surgically Treated Teeth</brief_title>
  <official_title>The Efficacy of Adjunctive Antimicrobial Photodynamic Therapy for Residual Pockets in Previously Surgically Treated Teeth: a Randomized Clinical Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Manitoba</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Manitoba</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>
      Traditionally, periodontal gum surgery has been used as a method to gain access to inflamed&#xD;
      periodontal pockets around teeth. The outcome of these surgeries, however, is not always&#xD;
      successful as there can be recurrence of inflammation and disease. The objective of this&#xD;
      study is to assess the effectiveness of antimicrobial photodynamic therapy as an adjunct to&#xD;
      mechanical debridement of residual periodontal pockets in patients having undergone&#xD;
      periodontal surgery. Pocket probing depth (PPD), clinical attachment level (CAL), bleeding on&#xD;
      probing (BOP), and plaque index (PI) will be evaluated at all sites as measures of&#xD;
      inflammation and disease resolution.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A single-center, randomized, double-blind, longitudinal study will take place over 12 months.&#xD;
      Twenty-eight systemically healthy patients (i.e. absence of uncontrolled diabetes mellitus,&#xD;
      cancer, HIV, bone metabolic diseases, or disorders that compromise wound healing) enrolled in&#xD;
      a supportive periodontal therapy program and patients at the University of Manitoba Graduate&#xD;
      Periodontics Clinic, with at least one surgically treated site with a residual pocket probing&#xD;
      depth of ≥ 5mm and bleeding upon probing and having signed the informed consent will be&#xD;
      accepted into the study. PPD, CAL, BOP, and PI will be evaluated at these sites. A selected&#xD;
      participant will have a full mouth periodontal charting completed prior to baseline&#xD;
      measurements as part of their maintenance program.&#xD;
&#xD;
      Once selected the patient will see two clinicians: the examiner (hygienist) and operator&#xD;
      (resident).&#xD;
&#xD;
      The examiner records the data (PPD, CAL, BOP, PI) of the entire dentition including the&#xD;
      selected tooth or teeth, and provides preliminary hygiene treatment; the operator delivers&#xD;
      the test treatments.&#xD;
&#xD;
      The treatment assignments are concealed to the patient and the examiner. The operator is&#xD;
      unaware of previously recorded data except for pocket depth measurements and is not involved&#xD;
      in the post-treatment evaluations (3,6,12 months). At 12 months, a full mouth re-evaluation&#xD;
      will be completed by the examiner as part of the patient's maintenance program.&#xD;
&#xD;
      In the first visit, the examiner records the pocket probing depth, clinical attachment level,&#xD;
      presence of bleeding on probing, and plaque index at six sites on involved teeth. Thorough&#xD;
      scaling and root planing is performed under local anesthesia using periodontal curettes&#xD;
      (Gracey, Hu-Friedy, USA) and an ultrasonic device (Piezo, Ultradent, USA). Once complete, the&#xD;
      operator takes over. The patients are then randomly assigned to test or control groups by a&#xD;
      computer-generated table. The protocol may be: A, the laser is activated during treatments&#xD;
      with methylene blue; B, the laser is never activated during treatments with saline solution.&#xD;
&#xD;
      Antimicrobial photodynamic therapy is carried out in the residual pockets using the Periowave&#xD;
      system (Ondine Biomedical Inc, Vancouver, Canada). The photosensitizing agent is methylene&#xD;
      blue. Approximately 0.2 mL of the solution is applied over 60 seconds to each pocket with a&#xD;
      blunt-ended side-port irrigator. The site is illuminated for 60 seconds to activate the agent&#xD;
      using a disposable, light-diffusing tip that is introduced into the pocket via a diode laser&#xD;
      (wavelength = 675 nm, 160 mW of output power). The control treatment consists of the same&#xD;
      procedure, except that the photosensitizer is replaced with saline solution and the&#xD;
      light-diffusing tip is kept in the pocket for 60 seconds without activating the laser. The&#xD;
      patient is sent home with a home care package and oral hygiene instructions.&#xD;
&#xD;
      The second session is scheduled after 1 week. The operator applies the photosensitizer and&#xD;
      activates the laser according to protocol A or B. The examiner maintains the patients on a&#xD;
      3-month hygiene schedule and reassesses the participants 3, 6, and 12 months after the&#xD;
      treatment as well as reinforces oral hygiene instruction. Medical history, concomitant&#xD;
      medication, and all adverse events are recorded. Clinical parameters are measured the same&#xD;
      way as at baseline. All measurements will be calibrated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">January 8, 2019</start_date>
  <completion_date type="Anticipated">August 2020</completion_date>
  <primary_completion_date type="Anticipated">August 2020</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>Once selected the patient will see two clinicians: the examiner (hygienist) and operator (resident).&#xD;
The examiner records the data (PPD, CAL, BOP, PI) of the teeth, and provides preliminary hygiene treatment; the operator delivers the test treatments.&#xD;
The treatment assignments are concealed to the patient and the examiner. The operator is unaware of previously recorded data except for pocket depth measurements and is not involved in the post-treatment evaluations (3,6,12 months)</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in bleeding on probing (BOP)</measure>
    <time_frame>Initial, 3 months, 6 months, 12 months.</time_frame>
    <description>Change in the presence of bleeding upon probing on individual tooth surfaces at 3 months, 6 months, and 12 months compared to the initial measure.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in pocket probing depth (PPD)</measure>
    <time_frame>Initial, 3 months, 6 months, 12 months.</time_frame>
    <description>Change of the distance from the gingival margin to the tip of the periodontal probe at the bottom of the gingival pocket at 3 months, 6 months, and 12 months compared to the initial measure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of clinical attachment level (CAL)</measure>
    <time_frame>Initial, 3 months, 6 months, 12 months.</time_frame>
    <description>Change of the distance from the cemento-enamel junction to the tip of the periodontal probe at the bottom of the gingival pocket at 3 months, 6 months, and 12 months compared to the initial measure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of plaque index (PI)</measure>
    <time_frame>Initial, 3 months, 6 months, 12 months.</time_frame>
    <description>Change in the presence of plaque on individual tooth surfaces at 3 months, 6 months, and 12 months compared to the initial measure.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Periodontitis</condition>
  <arm_group>
    <arm_group_label>Treatment Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Antimicrobial photodynamic therapy with methylene blue applied to test site after mechanical debridement.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Photodynamic therapy laser is not activated with saline water in the test site after mechanical debridement.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Antimicrobial photodynamic therapy</intervention_name>
    <description>Antimicrobial photodynamic therapy is carried out in the residual pockets using the Periowave system. The photosensitizing agent is methylene blue. Approximately 0.2 mL of the solution is applied over 60 seconds to each pocket with a blunt-ended side-port irrigator. The site is illuminated for 60 seconds to activate the agent using a disposable, light-diffusing tip that is introduced into the pocket via a diode laser (wavelength = 675 nm, 160 mW of output power).</description>
    <arm_group_label>Treatment Group</arm_group_label>
    <other_name>&quot;Periowave&quot; trade name</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Placebo of photodynamic therapy</intervention_name>
    <description>The placebo of the antimicrobial photodynamic therapy is carried out in the residual pockets using the Periowave system. The photosensitizing agent is saline solution. Approximately 0.2 mL of the solution is applied over 60 seconds to each pocket with a blunt-ended side-port irrigator. The site is not illuminated (falsely activated) for 60 seconds using a disposable, light-diffusing tip that is introduced into the pocket via a diode laser (wavelength = 675 nm, 160 mW of output power).</description>
    <arm_group_label>Placebo Group</arm_group_label>
    <other_name>Placebo of &quot;Periowave&quot; trade name</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Systemically healthy&#xD;
&#xD;
          -  Enrolled in a supportive periodontal therapy program and a patient at the University&#xD;
             of Manitoba Graduate Periodontics Clinic&#xD;
&#xD;
          -  At least one surgically treated periodontal site with a residual pocket probing depth&#xD;
             of ≥ 5mm and bleeding upon probing&#xD;
&#xD;
          -  Completed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with uncontrolled diabetes mellitus&#xD;
&#xD;
          -  Patients with cancer&#xD;
&#xD;
          -  Patients with HIV&#xD;
&#xD;
          -  Patients with bone metabolic diseases&#xD;
&#xD;
          -  Patients with disorders that compromise wound healing&#xD;
&#xD;
          -  Patients undergoing radiation or immunosuppressive therapy&#xD;
&#xD;
          -  Pregnancy or lactation&#xD;
&#xD;
          -  Have had antibiotics therapy within the last three months&#xD;
&#xD;
          -  Confirmed or suspected intolerance to methylene blue&#xD;
&#xD;
          -  Any physical limitations or restrictions that might preclude normal oral hygiene&#xD;
             procedures&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anastasia Cholakis, M Dent</last_name>
    <role>Study Director</role>
    <affiliation>University of Manitoba</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Manitoba</name>
      <address>
        <city>Winnipeg</city>
        <state>Manitoba</state>
        <zip>R3E 0W3</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
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  <verification_date>September 2019</verification_date>
  <study_first_submitted>November 23, 2018</study_first_submitted>
  <study_first_submitted_qc>November 27, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 28, 2018</study_first_posted>
  <last_update_submitted>September 29, 2019</last_update_submitted>
  <last_update_submitted_qc>September 29, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 1, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Manitoba</investigator_affiliation>
    <investigator_full_name>Javier Cabrales</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Periodontitis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anti-Infective Agents</mesh_term>
    <mesh_term>Anti-Bacterial Agents</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>All IPD will be made available in an anonymized (de-identified) form.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>After conclusion of the study up until 5 years after completion of the study.</ipd_time_frame>
  </patient_data>
  <pending_results>
    <submitted>November 2, 2020</submitted>
    <returned>November 24, 2020</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT03757260
org study id: B2018:012
nct id: NCT03757260
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Traditionally, periodontal gum surgery has been used as a method to gain access to inflamed
      periodontal pockets around teeth. The outcome of these surgeries, however, is not always
      successful as there can be recurrence of inflammation and disease. The objective of this
      study is to assess the effectiveness of antimicrobial photodynamic therapy as an adjunct to
      mechanical debridement of residual periodontal pockets in patients having undergone
      periodontal surgery. Pocket probing depth (PPD), clinical attachment level (CAL), bleeding on
      probing (BOP), and plaque index (PI) will be evaluated at all sites as measures of
      inflammation and disease resolution.
A single-center, randomized, double-blind, longitudinal study will take place over 12 months.
      Twenty-eight systemically healthy patients (i.e. absence of uncontrolled diabetes mellitus,
      cancer, HIV, bone metabolic diseases, or disorders that compromise wound healing) enrolled in
      a supportive periodontal therapy program and patients at the University of Manitoba Graduate
      Periodontics Clinic, with at least one surgically treated site with a residual pocket probing
      depth of ≥ 5mm and bleeding upon probing and having signed the informed consent will be
      accepted into the study. PPD, CAL, BOP, and PI will be evaluated at these sites. A selected
      participant will have a full mouth periodontal charting completed prior to baseline
      measurements as part of their maintenance program.

      Once selected the patient will see two clinicians: the examiner (hygienist) and operator
      (resident).

      The examiner records the data (PPD, CAL, BOP, PI) of the entire dentition including the
      selected tooth or teeth, and provides preliminary hygiene treatment; the operator delivers
      the test treatments.

      The treatment assignments are concealed to the patient and the examiner. The operator is
      unaware of previously recorded data except for pocket depth measurements and is not involved
      in the post-treatment evaluations (3,6,12 months). At 12 months, a full mouth re-evaluation
      will be completed by the examiner as part of the patient's maintenance program.

      In the first visit, the examiner records the pocket probing depth, clinical attachment level,
      presence of bleeding on probing, and plaque index at six sites on involved teeth. Thorough
      scaling and root planing is performed under local anesthesia using periodontal curettes
      (Gracey, Hu-Friedy, USA) and an ultrasonic device (Piezo, Ultradent, USA). Once complete, the
      operator takes over. The patients are then randomly assigned to test or control groups by a
      computer-generated table. The protocol may be: A, the laser is activated during treatments
      with methylene blue; B, the laser is never activated during treatments with saline solution.

      Antimicrobial photodynamic therapy is carried out in the residual pockets using the Periowave
      system (Ondine Biomedical Inc, Vancouver, Canada). The photosensitizing agent is methylene
      blue. Approximately 0.2 mL of the solution is applied over 60 seconds to each pocket with a
      blunt-ended side-port irrigator. The site is illuminated for 60 seconds to activate the agent
      using a disposable, light-diffusing tip that is introduced into the pocket via a diode laser
      (wavelength = 675 nm, 160 mW of output power). The control treatment consists of the same
      procedure, except that the photosensitizer is replaced with saline solution and the
      light-diffusing tip is kept in the pocket for 60 seconds without activating the laser. The
      patient is sent home with a home care package and oral hygiene instructions.

      The second session is scheduled after 1 week. The operator applies the photosensitizer and
      activates the laser according to protocol A or B. The examiner maintains the patients on a
      3-month hygiene schedule and reassesses the participants 3, 6, and 12 months after the
      treatment as well as reinforces oral hygiene instruction. Medical history, concomitant
      medication, and all adverse events are recorded. Clinical parameters are measured the same
      way as at baseline. All measurements will be calibrated.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
masking description: Once selected the patient will see two clinicians: the examiner (hygienist) and operator (resident).
The examiner records the data (PPD, CAL, BOP, PI) of the teeth, and provides preliminary hygiene treatment; the operator delivers the test treatments.
The treatment assignments are concealed to the patient and the examiner. The operator is unaware of previously recorded data except for pocket depth measurements and is not involved in the post-treatment evaluations (3,6,12 months)
measure: Change in bleeding on probing (BOP)
time frame: Initial, 3 months, 6 months, 12 months.
description: Change in the presence of bleeding upon probing on individual tooth surfaces at 3 months, 6 months, and 12 months compared to the initial measure.
measure: Change in pocket probing depth (PPD)
time frame: Initial, 3 months, 6 months, 12 months.
description: Change of the distance from the gingival margin to the tip of the periodontal probe at the bottom of the gingival pocket at 3 months, 6 months, and 12 months compared to the initial measure.
measure: Change of clinical attachment level (CAL)
time frame: Initial, 3 months, 6 months, 12 months.
description: Change of the distance from the cemento-enamel junction to the tip of the periodontal probe at the bottom of the gingival pocket at 3 months, 6 months, and 12 months compared to the initial measure.
measure: Change of plaque index (PI)
time frame: Initial, 3 months, 6 months, 12 months.
description: Change in the presence of plaque on individual tooth surfaces at 3 months, 6 months, and 12 months compared to the initial measure.
arm group label: Treatment Group
arm group type: Experimental
description: Antimicrobial photodynamic therapy with methylene blue applied to test site after mechanical debridement.
arm group label: Placebo Group
arm group type: Placebo Comparator
description: Photodynamic therapy laser is not activated with saline water in the test site after mechanical debridement.
intervention type: Device
intervention name: Antimicrobial photodynamic therapy
description: Antimicrobial photodynamic therapy is carried out in the residual pockets using the Periowave system. The photosensitizing agent is methylene blue. Approximately 0.2 mL of the solution is applied over 60 seconds to each pocket with a blunt-ended side-port irrigator. The site is illuminated for 60 seconds to activate the agent using a disposable, light-diffusing tip that is introduced into the pocket via a diode laser (wavelength = 675 nm, 160 mW of output power).
arm group label: Treatment Group
other name: "Periowave" trade name
intervention type: Device
intervention name: Placebo of photodynamic therapy
description: The placebo of the antimicrobial photodynamic therapy is carried out in the residual pockets using the Periowave system. The photosensitizing agent is saline solution. Approximately 0.2 mL of the solution is applied over 60 seconds to each pocket with a blunt-ended side-port irrigator. The site is not illuminated (falsely activated) for 60 seconds using a disposable, light-diffusing tip that is introduced into the pocket via a diode laser (wavelength = 675 nm, 160 mW of output power).
arm group label: Placebo Group
other name: Placebo of "Periowave" trade name
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Anastasia Cholakis, M Dent
role: Study Director
affiliation: University of Manitoba
facility: 
country: Canada
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PMID: 16788934
responsible party type: Principal Investigator
investigator affiliation: University of Manitoba
investigator full name: Javier Cabrales
investigator title: Principal Investigator
mesh term: Periodontitis
mesh term: Anti-Infective Agents
mesh term: Anti-Bacterial Agents
sharing ipd: Yes
ipd description: All IPD will be made available in an anonymized (de-identified) form.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: After conclusion of the study up until 5 years after completion of the study.
submitted: November 2, 2020
returned: November 24, 2020