<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/NCT03270254</url>
  </required_header>
  <id_info>
    <org_study_id>STH19404</org_study_id>
    <nct_id>NCT03270254</nct_id>
  </id_info>
  <brief_title>Photodynamic Therapy Plus Root Debridement in Gum Disease Treatment V2</brief_title>
  <acronym>PDTV2</acronym>
  <official_title>A Split-mouth Randomised Controlled Clinical Trial of Photodynamic Therapy (PDT) as Adjunctive Therapy to Root Surface Debridement (RSD), Compared to RSD Alone in the Treatment of Residual Periodontal Pockets in Patients With Chronic Periodontitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sheffield Teaching Hospitals NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ondine Biomedical Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Sheffield Teaching Hospitals NHS Foundation Trust</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>
      Gum disease is a common disease, which affects 45% of the UK adult dentate population. It is&#xD;
      caused by bacteria in dental plaque, which produces inflammation and a deepening of the&#xD;
      natural crevice between the gum and the tooth surface. A crevice of 3mm is considered to be&#xD;
      within the normal range, but anything ≥4mm is considered to be abnormal and is called a&#xD;
      &quot;pocket&quot;. Standard treatment of gum disease is mechanical cleaning aimed at removing bacteria&#xD;
      off the root surfaces of the teeth. For most teeth, in the majority of patients, this can be&#xD;
      achieved by root surface debridement (RSD), which involves passing instruments into the gum&#xD;
      pockets to clean the roots. Previous studies have shown that the outcome of treatment is less&#xD;
      effective when the pockets are deeper, or where there is bone or root anatomy which makes&#xD;
      access for RSD difficult. In such instances additional approaches, such as repeating RSD,&#xD;
      surgical access, or the additional use of antibiotics are considered. This clinical study&#xD;
      will investigate the benefits and drawbacks of using a light source and dye (photodynamic&#xD;
      therapy - PDT) as an additional treatment compared to the standard treatment of RSD alone.&#xD;
      Patients with chronic gum problems who have undergone 1 cycle of RSD, but have residual&#xD;
      pockets will be invited to join the study. All residual pockets will be treated with the&#xD;
      conventional treatment of RSD. Following a random allocation process the residual pockets in&#xD;
      half the mouth will receive additional treatment with PDT at the same appointment. Patients&#xD;
      will be followed up for 3 months to evaluate the clinical benefits and any side effects. The&#xD;
      aim of the study is therefore to evaluate if this localised, simple treatment can add benefit&#xD;
      to RSD alone, thus reducing the need for antibiotics or surgery to treat residual pockets.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will be a single centre, examiner masked, two arm, split mouth, randomized&#xD;
      controlled clinical trial, to evaluate the clinical effectiveness of mechanical cleaning&#xD;
      (RSD) plus additional use of a light activated dye (photodynamic therapy-PDT) compared to&#xD;
      mechanical cleaning alone, in the treatment of residual pockets, in patients with chronic gum&#xD;
      disease. The null hypothesis is that there is no difference between RSD and the additional&#xD;
      use of PDT compared to RSD alone, when treating patients with chronic gum disease. The local&#xD;
      delivery treatment of PDT requires the low power light to be shone into the pocket for 1&#xD;
      minute in order to activate the dye which kills the bacteria. For this reason it is a&#xD;
      treatment which is more suited to treating localised rather than widespread disease. Thus,&#xD;
      patients with chronic gum problems who have had a cycle of treatment with the hygienist, but&#xD;
      have a few residual pockets will be selected for this study. Subjects will be recruited from&#xD;
      patients attending the hygienist following a first cycle of RSD, who have sufficient&#xD;
      remaining disease to represent a meaningful challenge. This reflects the normal care pathway&#xD;
      for patients, where simple approaches to treatment are followed up with more complicated&#xD;
      therapy for any areas which fail to respond. A power calculation has shown that 29 patients&#xD;
      are expected to be enough to see if PDT &amp; RSD can produce better gum health than RSD alone.&#xD;
      However, to account for unexpected patient withdrawals, 35 patients will be recruited to this&#xD;
      study. The staff hygienists in the department are capable of providing treatment for 60-90&#xD;
      patients over a 3-month period. Out of these patients those with more severe disease are&#xD;
      likely to have residual pockets that require further cycles of RSD. Thus there is potentially&#xD;
      a good population of patients attending Charles Clifford Dental Hospital to recruit from. All&#xD;
      residual sites within a subject who participates in the study will be treated by mechanical&#xD;
      cleaning. This is the standard treatment which would apply for most patients in this&#xD;
      situation. A random allocation procedure will be used to designate sections of the mouth to&#xD;
      receive additional treatment with the PDT. This will not be made known to the operator&#xD;
      performing the RSD until after they have completed that aspect of treatment. This helps&#xD;
      reduce bias as the operator will clean all sites to an equivalent standard. The split mouth&#xD;
      approach means that the patient will act as their own control. This helps reduce the numbers&#xD;
      of patients which need to be recruited as compared to a study with 2 parallel groups, where&#xD;
      each group receives a different treatment. The suggested disadvantage of a split mouth&#xD;
      design, is the fact that there may be some contamination of RSD sites only with the action of&#xD;
      a chemical remote from the site it was originally placed in. However, in this study the&#xD;
      chemical needs to be activated by the light, and therefore it is easier to control the&#xD;
      activity of PDT therapy to the sites it was designated to be used in. For this reason there&#xD;
      needs to be a gap between the section of the mouth treated by adjunctive PDT &amp; RSD, compared&#xD;
      to the section of the mouth where RSD alone is the treatment. No additional appointments will&#xD;
      be required of the patients compared to the normal protocol as they will receive the &quot;gold&#xD;
      standard&quot; treatment of mechanical cleaning (RSD) in all sites. The additional requirements of&#xD;
      the study will be the time it takes to provide treatment using PDT. This is anticipated to be&#xD;
      between 5-15 minutes depending upon the number and distribution of sites throughout the&#xD;
      mouth. Sample collection of bacterial plaque and gum fluid from 2 sites per patient will take&#xD;
      an additional 5-10 minutes. The normal treatment time at this stage of treatment would be 60&#xD;
      minutes and this will be extended to 70-85 minutes for the study purposes. None of the&#xD;
      additional procedures are likely to cause discomfort. The 3 month re-assessment examination&#xD;
      will require repeat sample collection of bacterial plaque and gum fluid from 2 sites which&#xD;
      will take an additional 5-10 minutes. Thus the standard patient reassessment appointment of&#xD;
      60 minutes will be extended to 65-70 minutes. The full process from recruitment of patients&#xD;
      to writing up this student project is expected to be finished within seven to nine months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 13, 2017</start_date>
  <completion_date type="Actual">September 19, 2018</completion_date>
  <primary_completion_date type="Actual">September 19, 2018</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>Single Group Assignment</intervention_model>
    <intervention_model_description>Randomised Split mouth</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>The patient and Dentist will both be aware of the type of treatment, The researcher analysing the collected samples will be blind to treatment</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Pocket depth change</measure>
    <time_frame>3 months</time_frame>
    <description>The difference in mean change of probing pocket depth in millimetres between the test and control sites</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in clinical attachment</measure>
    <time_frame>3 months</time_frame>
    <description>The difference in mean change of clinical attachment loss in millimetres between the test and control sites.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bleeding on probing</measure>
    <time_frame>3 months</time_frame>
    <description>The percentage difference of bleeding on probing between tests and controls.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Probing depths originally ≥ 6mm.</measure>
    <time_frame>3 months</time_frame>
    <description>The percentage difference of sites with probing depths originally ≥ 6mm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Probing depths originally ≤3mm</measure>
    <time_frame>3 months</time_frame>
    <description>The percentage increase of sites with probing depths originally ≤3mm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of sites improving by ≥2mm</measure>
    <time_frame>3 months</time_frame>
    <description>The total number of sites improving by ≥2mm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of sites improving by ≥2mm</measure>
    <time_frame>3 months</time_frame>
    <description>The percentage of sites improving by ≥2mm</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Periodontitis</condition>
  <arm_group>
    <arm_group_label>root surface debridement (RSD)</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Standard care - root surface debridement (RSD)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>light activated dye (PDT)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>light activated dye photodynamic therapy (PDT)</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>light activated dye photodynamic therapy (PDT)</intervention_name>
    <description>light activated dye photodynamic therapy-PDT to periodontal pockets</description>
    <arm_group_label>light activated dye (PDT)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients ≥ 30 years old&#xD;
&#xD;
          -  Presence of at least 20 remaining teeth&#xD;
&#xD;
          -  Patients diagnosed with moderate to severe chronic periodontitis, according to&#xD;
             Armitage 1999 classification&#xD;
&#xD;
          -  Have undergone a minimum of one cycle of full mouth nonsurgical root surface&#xD;
             debridement.&#xD;
&#xD;
          -  A minimum of 8 residual periodontal pockets (≥4mm) per patient and a maximum of 24.&#xD;
             Amongst these, at least one site per half mouth must exhibit pocket depths of ≥ 6 mm.&#xD;
&#xD;
          -  Pockets distribution should allow for split mouth design using sextants in a diagonal&#xD;
             orientation.&#xD;
&#xD;
          -  Received no active periodontal treatment for the last three months.&#xD;
&#xD;
          -  Full mouth plaque score and full mouth bleeding score ≤ 30%.&#xD;
&#xD;
          -  Sites in the other half of the mouth to be separated by one or more teeth (avoids&#xD;
             photosensitising agent affecting the other half).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with systemic diseases that may alter the response to treatment and healing&#xD;
             in periodontal diseases.&#xD;
&#xD;
          -  Pregnancy and lactation.&#xD;
&#xD;
          -  The use of systemic or local antibiotic in the past three months.&#xD;
&#xD;
          -  The need for antibiotic prophylaxis before periodontal treatment.&#xD;
&#xD;
          -  Use of antimicrobial mouth rinses in the preceding two months.&#xD;
&#xD;
          -  The use of any pharmacological agents that could influence the study outcome or&#xD;
             inflammatory indicators (e.g. patients currently on photosensitizing medications).&#xD;
&#xD;
          -  Confirmed or suspected allergy or hypersensitivity to methylene blue.&#xD;
&#xD;
          -  Confirmed or suspected allergy or hypersensitivity to chlorhexidine.&#xD;
&#xD;
          -  Confirmed or suspected allergy or hypersensitivity to polymethyl methacrylate (PMMA).&#xD;
&#xD;
          -  Patients with severe glucose-6-phosphate dehydrogenase (G6PD) deficiency.&#xD;
&#xD;
          -  Inability to perform proper oral hygiene due to physical impairment.&#xD;
&#xD;
          -  Patients unable to consent for themselves.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gareth Griffiths</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Sheffield</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sheffield Teaching Hospitals NHS Trust</name>
      <address>
        <city>Sheffield</city>
        <state>South Yorkshire</state>
        <zip>S10 2JF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>August 30, 2017</study_first_submitted>
  <study_first_submitted_qc>August 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 1, 2017</study_first_posted>
  <last_update_submitted>May 28, 2019</last_update_submitted>
  <last_update_submitted_qc>May 28, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 30, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Periodontitis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>The research findings will probably be published in a scientific journal</ipd_description>
  </patient_data>
  <!-- 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/NCT03270254
org study id: STH19404
nct id: NCT03270254
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Gum disease is a common disease, which affects 45% of the UK adult dentate population. It is
      caused by bacteria in dental plaque, which produces inflammation and a deepening of the
      natural crevice between the gum and the tooth surface. A crevice of 3mm is considered to be
      within the normal range, but anything ≥4mm is considered to be abnormal and is called a
      "pocket". Standard treatment of gum disease is mechanical cleaning aimed at removing bacteria
      off the root surfaces of the teeth. For most teeth, in the majority of patients, this can be
      achieved by root surface debridement (RSD), which involves passing instruments into the gum
      pockets to clean the roots. Previous studies have shown that the outcome of treatment is less
      effective when the pockets are deeper, or where there is bone or root anatomy which makes
      access for RSD difficult. In such instances additional approaches, such as repeating RSD,
      surgical access, or the additional use of antibiotics are considered. This clinical study
      will investigate the benefits and drawbacks of using a light source and dye (photodynamic
      therapy - PDT) as an additional treatment compared to the standard treatment of RSD alone.
      Patients with chronic gum problems who have undergone 1 cycle of RSD, but have residual
      pockets will be invited to join the study. All residual pockets will be treated with the
      conventional treatment of RSD. Following a random allocation process the residual pockets in
      half the mouth will receive additional treatment with PDT at the same appointment. Patients
      will be followed up for 3 months to evaluate the clinical benefits and any side effects. The
      aim of the study is therefore to evaluate if this localised, simple treatment can add benefit
      to RSD alone, thus reducing the need for antibiotics or surgery to treat residual pockets.
The study will be a single centre, examiner masked, two arm, split mouth, randomized
      controlled clinical trial, to evaluate the clinical effectiveness of mechanical cleaning
      (RSD) plus additional use of a light activated dye (photodynamic therapy-PDT) compared to
      mechanical cleaning alone, in the treatment of residual pockets, in patients with chronic gum
      disease. The null hypothesis is that there is no difference between RSD and the additional
      use of PDT compared to RSD alone, when treating patients with chronic gum disease. The local
      delivery treatment of PDT requires the low power light to be shone into the pocket for 1
      minute in order to activate the dye which kills the bacteria. For this reason it is a
      treatment which is more suited to treating localised rather than widespread disease. Thus,
      patients with chronic gum problems who have had a cycle of treatment with the hygienist, but
      have a few residual pockets will be selected for this study. Subjects will be recruited from
      patients attending the hygienist following a first cycle of RSD, who have sufficient
      remaining disease to represent a meaningful challenge. This reflects the normal care pathway
      for patients, where simple approaches to treatment are followed up with more complicated
      therapy for any areas which fail to respond. A power calculation has shown that 29 patients
      are expected to be enough to see if PDT & RSD can produce better gum health than RSD alone.
      However, to account for unexpected patient withdrawals, 35 patients will be recruited to this
      study. The staff hygienists in the department are capable of providing treatment for 60-90
      patients over a 3-month period. Out of these patients those with more severe disease are
      likely to have residual pockets that require further cycles of RSD. Thus there is potentially
      a good population of patients attending Charles Clifford Dental Hospital to recruit from. All
      residual sites within a subject who participates in the study will be treated by mechanical
      cleaning. This is the standard treatment which would apply for most patients in this
      situation. A random allocation procedure will be used to designate sections of the mouth to
      receive additional treatment with the PDT. This will not be made known to the operator
      performing the RSD until after they have completed that aspect of treatment. This helps
      reduce bias as the operator will clean all sites to an equivalent standard. The split mouth
      approach means that the patient will act as their own control. This helps reduce the numbers
      of patients which need to be recruited as compared to a study with 2 parallel groups, where
      each group receives a different treatment. The suggested disadvantage of a split mouth
      design, is the fact that there may be some contamination of RSD sites only with the action of
      a chemical remote from the site it was originally placed in. However, in this study the
      chemical needs to be activated by the light, and therefore it is easier to control the
      activity of PDT therapy to the sites it was designated to be used in. For this reason there
      needs to be a gap between the section of the mouth treated by adjunctive PDT & RSD, compared
      to the section of the mouth where RSD alone is the treatment. No additional appointments will
      be required of the patients compared to the normal protocol as they will receive the "gold
      standard" treatment of mechanical cleaning (RSD) in all sites. The additional requirements of
      the study will be the time it takes to provide treatment using PDT. This is anticipated to be
      between 5-15 minutes depending upon the number and distribution of sites throughout the
      mouth. Sample collection of bacterial plaque and gum fluid from 2 sites per patient will take
      an additional 5-10 minutes. The normal treatment time at this stage of treatment would be 60
      minutes and this will be extended to 70-85 minutes for the study purposes. None of the
      additional procedures are likely to cause discomfort. The 3 month re-assessment examination
      will require repeat sample collection of bacterial plaque and gum fluid from 2 sites which
      will take an additional 5-10 minutes. Thus the standard patient reassessment appointment of
      60 minutes will be extended to 65-70 minutes. The full process from recruitment of patients
      to writing up this student project is expected to be finished within seven to nine months.
allocation: Randomized
intervention model: Single Group Assignment
intervention model description: Randomised Split mouth
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: The patient and Dentist will both be aware of the type of treatment, The researcher analysing the collected samples will be blind to treatment
measure: Pocket depth change
time frame: 3 months
description: The difference in mean change of probing pocket depth in millimetres between the test and control sites
measure: Change in clinical attachment
time frame: 3 months
description: The difference in mean change of clinical attachment loss in millimetres between the test and control sites.
measure: Bleeding on probing
time frame: 3 months
description: The percentage difference of bleeding on probing between tests and controls.
measure: Probing depths originally ≥ 6mm.
time frame: 3 months
description: The percentage difference of sites with probing depths originally ≥ 6mm.
measure: Probing depths originally ≤3mm
time frame: 3 months
description: The percentage increase of sites with probing depths originally ≤3mm
measure: Number of sites improving by ≥2mm
time frame: 3 months
description: The total number of sites improving by ≥2mm
measure: Percentage of sites improving by ≥2mm
time frame: 3 months
description: The percentage of sites improving by ≥2mm
arm group label: root surface debridement (RSD)
arm group type: No Intervention
description: Standard care - root surface debridement (RSD)
arm group label: light activated dye (PDT)
arm group type: Active Comparator
description: light activated dye photodynamic therapy (PDT)
intervention type: Device
intervention name: light activated dye photodynamic therapy (PDT)
description: light activated dye photodynamic therapy-PDT to periodontal pockets
arm group label: light activated dye (PDT)
criteria: 
gender: All
minimum age: 30 Years
maximum age: N/A
healthy volunteers: No
last name: Gareth Griffiths
role: Principal Investigator
affiliation: University of Sheffield
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Periodontitis
sharing ipd: Undecided
ipd description: The research findings will probably be published in a scientific journal