<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/NCT03018795</url>
  </required_header>
  <id_info>
    <org_study_id>25901600-2858</org_study_id>
    <nct_id>NCT03018795</nct_id>
  </id_info>
  <brief_title>Ozone Therapy as an Adjunct to the Surgical Treatment of Peri-implantitis</brief_title>
  <official_title>The Effect of Ozone Therapy as an Adjunct to the Surgical Treatment of Peri-implantitis: A Randomized Controlled Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gazi University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Gazi University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Decontamination procedure is a challenging factor that affects the success of surgical&#xD;
      regenerative therapy (SRT) of peri-implantitis. The purpose of the present study was to&#xD;
      determine the impact of additional ozone therapy for the decontamination of implant surfaces&#xD;
      in SRT of peri-implantitis. A total of 21 patients with moderate or advanced peri-implantitis&#xD;
      were randomly allocated to the test group (ozone group) with the use of sterile saline with&#xD;
      additional ozone therapy or the control group with sterile saline alone for decontamination&#xD;
      of the implant surfaces in SRT of peri-implantitis. Clinical and radiographic outcomes were&#xD;
      evaluated at baseline and 6 months postoperatively&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Peri-implant diseases are described as inflammatory processes in the tissues surrounding&#xD;
      implants in response to mainly microbial biofilms on the surface of the implants (Zitzmann&#xD;
      and Berglundh 2008). Peri-implant mucositis is described as an inflammatory reaction&#xD;
      triggered by microbial biofilms without any loss of peri-implant bone, while peri-implantitis&#xD;
      is characterized by bleeding when probed and/or suppuration with further loss of the&#xD;
      peri-implant bone (Lindhe and Meyle 2008; Lang and Berglundh 2011).&#xD;
&#xD;
      Since microbial biofilms play a major role in the etiology (Becker et al. 1990; Quirynen et&#xD;
      al. 2002), it has been considered that elimination of microbial pathogens is mandatory in the&#xD;
      treatment of peri-implant diseases (Mombelli and Lang 1994; Schwarz et al. 2006). The&#xD;
      objectives of peri-implantitis therapy are implant surface decontamination to resolve&#xD;
      inflammation resolution while preserving the implant supporting tissues (Lindhe and Meyle&#xD;
      2008; Heitz-Mayfield and Lang 2010).&#xD;
&#xD;
      Several implant decontamination methods have been suggested, including mechanical&#xD;
      debridement, chemical therapy (applications of root conditioners, disinfectants, and local&#xD;
      and systemic antibiotic therapy) (Heitz-Mayfield et al. 2012; Wohlfahrt et al. 2012) and&#xD;
      surgical procedures aiming to remove bacteria, and smooth, decontaminate and detoxify the&#xD;
      implant surface (Froum et al. 2012; Schwarz et al. 2013). However, there is as yet no&#xD;
      consensus on the most effective protocol for implant surface detoxification (Suarez et al.&#xD;
      2013).&#xD;
&#xD;
      Ozone has a strong oxidation effect with remarkable antimicrobial potential and can be used&#xD;
      as a disinfectant in clinical applications of dentistry (Iliadis and Millar 2013). A previous&#xD;
      study reported that ozone has powerful antimicrobial activity in response to anaerobic&#xD;
      periodontal pathogenic microorganisms and may have the potential to be used as an adjunctive&#xD;
      tool in non-surgical periodontal therapy in periodontitis patients (Eick et al. 2012). Ozone&#xD;
      therapy can promote haemostasis, enhance the release of growth factors and local oxygen&#xD;
      supply, upregulate cellular antioxidant enzymes and inhibit bacterial proliferation (Ozdemir&#xD;
      et al. 2013). However, current literature has little information regarding the antimicrobial&#xD;
      activity of ozone in the treatment of peri-implant diseases. A previous randomized, clinical&#xD;
      study showed that ozone therapy reduced inflammation in the treatment of peri-implant&#xD;
      mucositis (McKenna et al. 2013). Another in-vitro trial reported that in the reduction of&#xD;
      adherent bacteria on titanium, gaseous ozone showed selective efficacy without any adverse&#xD;
      effect on the surface structures of the titanium surfaces or the adhesion and proliferation&#xD;
      of osteoblastic cells (Huser-Gerspach et al. 2012).&#xD;
&#xD;
      Non-surgical therapy alone has been reported to be inadequate for the treatment of moderate&#xD;
      and severe forms of peri-implantitis and therefore surgical therapy is frequently required&#xD;
      (Lindhe and Meyle 2008). The goals of surgical therapy of peri-implantitis are mainly to be&#xD;
      able to access areas for mechanical debridement and implant surface decontamination and to&#xD;
      reconstruct the anatomic conditions to improve plaque control and to eliminate the&#xD;
      pathological peri-implant pockets (Esposito et al. 2012; Roos-Jansaker et al. 2014). This can&#xD;
      be achieved with resection or with procedures of bone regeneration such as guided bone&#xD;
      regeneration (Roos-Jansaker et al. 2003; Schou et al 2004; Sahrmann et al. 2011).&#xD;
&#xD;
      Studies have evaluated the combination of various regenerative biological agents and&#xD;
      techniques for surgical regenerative therapy (SRT) of peri-implantitis and clinical and&#xD;
      radiological improvements following different bone augmentation procedures have been reported&#xD;
      (Claffey et al. 2008; Schwarz et al. 2009; Roos-Jansaker et al. 2011; Renvert et al. 2012). A&#xD;
      long-term, clinical study demonstrated that vertical peri-implant bone defects (PBDs) may be&#xD;
      actively treated by regenerative surgical means, using a bone substitute alone or in&#xD;
      combination with a membrane (Roos-Jansaker et al. 2014).&#xD;
&#xD;
      Platelet concentrates are preferred in periodontal surgical procedures for the purpose of&#xD;
      accelerating angiogenesis, stimulating the activity of osteoblasts and fibroblasts, and&#xD;
      obtaining regeneration of hard and soft tissues, including stem cells and growth factors (Del&#xD;
      Fabbro et al. 2011). These materials can be used alone or in combination with bone grafts or&#xD;
      barrier membranes. In studies employing bone grafts with the use of platelet rich fibrin&#xD;
      (PRF) or PRF alone around PBDs it has been reported that PRF leads to increased new bone&#xD;
      formation and a higher bone to implant contact ratio (Lee et al. 2012; Simsek et al. 2016). A&#xD;
      recent study reported that treatment of peri-implantitis using PRF was clinically more&#xD;
      effective than with access flap surgery alone. It was also concluded in the study that PRF&#xD;
      improves the outcomes of surgical peri-implantitis treatment (Hamzacebi et al. 2015).&#xD;
&#xD;
      There have been recent developments of various techniques using platelet concentrate to&#xD;
      provide different rates of platelets, leukocytes, growth factors, stem cells and fibrin&#xD;
      matrix. Sacco developed concentrated growth factors (CGF) as a therapeutic protocol obtained&#xD;
      by separating the venous blood centrifuged using a special device in the same manner as PRF&#xD;
      (Rodella et al. 2011). It was also argued that centrifugation at a different speed provides a&#xD;
      larger, denser fibrin matrix compared to PRF, which results in improved regenerative capacity&#xD;
      and greater versatility (Sohn et al. 2009). Some recent studies have reported that CGF&#xD;
      accelerates new bone formation related to guided bone regeneration (Sohn et al. 2011; Kim et&#xD;
      al. 2014).&#xD;
&#xD;
      The purpose of this randomized, controlled clinical study was to evaluate the clinical and&#xD;
      radiological results of implant surface decontamination using sterile saline alone or in&#xD;
      combination with ozone therapy applied as surgical regenerative treatment for&#xD;
      peri-implantitis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">September 2016</completion_date>
  <primary_completion_date type="Actual">January 2016</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>probing depth of peri-implantitis sites</measure>
    <time_frame>6 months postoperatively</time_frame>
    <description>measured as the distance between the deepest site of the pocket to the peri-implant mucosal margin</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>bone loss of peri-implant defects</measure>
    <time_frame>6 months postoperatively</time_frame>
    <description>Measurements were taken of mesial and distal distances between the first bone to implant contact and bone loss (BL) in the implant shoulder</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Peri-Implantitis</condition>
  <arm_group>
    <arm_group_label>Ozone Group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Decontamination of implant surfaces with saline irrigation and additional ozone therapy in combination with regenerative surgery</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Decontamination of implant surfaces with saline irrigation alone in combination with regenerative surgery</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Decontamination of implant surfaces</intervention_name>
    <description>Decontamination of implant surfaces in combination with regenerative surgery</description>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_label>Ozone Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. age &gt; 18 years,&#xD;
&#xD;
          2. presence of peri-implantitis exhibiting one of the defect configurations as defined by&#xD;
             either a Class Ib (buccal dehiscence + semicircumferential bone resorption), Class Ic&#xD;
             (i.e. buccal dehiscence + circular bone resorption) or Class Ie (i.e. circumferential&#xD;
             bone resorption) with a probing depth of &gt;6 mm&#xD;
&#xD;
          3. radiographic bone loss ≥2 mm on at least at one implant surface,&#xD;
&#xD;
          4. peri-implant sites with bleeding or suppuration after probing,&#xD;
&#xD;
          5. no implant mobility,&#xD;
&#xD;
          6. no evidence of occlusal overload&#xD;
&#xD;
          7. non-smoker.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. serious systemic disease that would contraindicate for periodontal surgery (i.e.&#xD;
             diabetes (HbA1c &lt; 7),&#xD;
&#xD;
          2. prophylactic antibiotics required or systemic antibiotic administration during the&#xD;
             past 3 months, and (3) placement, and prosthetic loading of implants within the past 1&#xD;
             year.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Berrin Unsal, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Prof Dr</affiliation>
  </overall_official>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>January 10, 2017</study_first_submitted>
  <study_first_submitted_qc>January 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 12, 2017</study_first_posted>
  <last_update_submitted>January 10, 2017</last_update_submitted>
  <last_update_submitted_qc>January 10, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 12, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Gazi University</investigator_affiliation>
    <investigator_full_name>Sıla Çağrı İşler</investigator_full_name>
    <investigator_title>PhD</investigator_title>
  </responsible_party>
  <keyword>peri-implantitis</keyword>
  <keyword>Surgical regenerative treatment</keyword>
  <keyword>ozone therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Peri-Implantitis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03018795
org study id: 25901600-2858
nct id: NCT03018795
lead sponsor: 
has dmc: No
Decontamination procedure is a challenging factor that affects the success of surgical
      regenerative therapy (SRT) of peri-implantitis. The purpose of the present study was to
      determine the impact of additional ozone therapy for the decontamination of implant surfaces
      in SRT of peri-implantitis. A total of 21 patients with moderate or advanced peri-implantitis
      were randomly allocated to the test group (ozone group) with the use of sterile saline with
      additional ozone therapy or the control group with sterile saline alone for decontamination
      of the implant surfaces in SRT of peri-implantitis. Clinical and radiographic outcomes were
      evaluated at baseline and 6 months postoperatively
Peri-implant diseases are described as inflammatory processes in the tissues surrounding
      implants in response to mainly microbial biofilms on the surface of the implants (Zitzmann
      and Berglundh 2008). Peri-implant mucositis is described as an inflammatory reaction
      triggered by microbial biofilms without any loss of peri-implant bone, while peri-implantitis
      is characterized by bleeding when probed and/or suppuration with further loss of the
      peri-implant bone (Lindhe and Meyle 2008; Lang and Berglundh 2011).

      Since microbial biofilms play a major role in the etiology (Becker et al. 1990; Quirynen et
      al. 2002), it has been considered that elimination of microbial pathogens is mandatory in the
      treatment of peri-implant diseases (Mombelli and Lang 1994; Schwarz et al. 2006). The
      objectives of peri-implantitis therapy are implant surface decontamination to resolve
      inflammation resolution while preserving the implant supporting tissues (Lindhe and Meyle
      2008; Heitz-Mayfield and Lang 2010).

      Several implant decontamination methods have been suggested, including mechanical
      debridement, chemical therapy (applications of root conditioners, disinfectants, and local
      and systemic antibiotic therapy) (Heitz-Mayfield et al. 2012; Wohlfahrt et al. 2012) and
      surgical procedures aiming to remove bacteria, and smooth, decontaminate and detoxify the
      implant surface (Froum et al. 2012; Schwarz et al. 2013). However, there is as yet no
      consensus on the most effective protocol for implant surface detoxification (Suarez et al.
      2013).

      Ozone has a strong oxidation effect with remarkable antimicrobial potential and can be used
      as a disinfectant in clinical applications of dentistry (Iliadis and Millar 2013). A previous
      study reported that ozone has powerful antimicrobial activity in response to anaerobic
      periodontal pathogenic microorganisms and may have the potential to be used as an adjunctive
      tool in non-surgical periodontal therapy in periodontitis patients (Eick et al. 2012). Ozone
      therapy can promote haemostasis, enhance the release of growth factors and local oxygen
      supply, upregulate cellular antioxidant enzymes and inhibit bacterial proliferation (Ozdemir
      et al. 2013). However, current literature has little information regarding the antimicrobial
      activity of ozone in the treatment of peri-implant diseases. A previous randomized, clinical
      study showed that ozone therapy reduced inflammation in the treatment of peri-implant
      mucositis (McKenna et al. 2013). Another in-vitro trial reported that in the reduction of
      adherent bacteria on titanium, gaseous ozone showed selective efficacy without any adverse
      effect on the surface structures of the titanium surfaces or the adhesion and proliferation
      of osteoblastic cells (Huser-Gerspach et al. 2012).

      Non-surgical therapy alone has been reported to be inadequate for the treatment of moderate
      and severe forms of peri-implantitis and therefore surgical therapy is frequently required
      (Lindhe and Meyle 2008). The goals of surgical therapy of peri-implantitis are mainly to be
      able to access areas for mechanical debridement and implant surface decontamination and to
      reconstruct the anatomic conditions to improve plaque control and to eliminate the
      pathological peri-implant pockets (Esposito et al. 2012; Roos-Jansaker et al. 2014). This can
      be achieved with resection or with procedures of bone regeneration such as guided bone
      regeneration (Roos-Jansaker et al. 2003; Schou et al 2004; Sahrmann et al. 2011).

      Studies have evaluated the combination of various regenerative biological agents and
      techniques for surgical regenerative therapy (SRT) of peri-implantitis and clinical and
      radiological improvements following different bone augmentation procedures have been reported
      (Claffey et al. 2008; Schwarz et al. 2009; Roos-Jansaker et al. 2011; Renvert et al. 2012). A
      long-term, clinical study demonstrated that vertical peri-implant bone defects (PBDs) may be
      actively treated by regenerative surgical means, using a bone substitute alone or in
      combination with a membrane (Roos-Jansaker et al. 2014).

      Platelet concentrates are preferred in periodontal surgical procedures for the purpose of
      accelerating angiogenesis, stimulating the activity of osteoblasts and fibroblasts, and
      obtaining regeneration of hard and soft tissues, including stem cells and growth factors (Del
      Fabbro et al. 2011). These materials can be used alone or in combination with bone grafts or
      barrier membranes. In studies employing bone grafts with the use of platelet rich fibrin
      (PRF) or PRF alone around PBDs it has been reported that PRF leads to increased new bone
      formation and a higher bone to implant contact ratio (Lee et al. 2012; Simsek et al. 2016). A
      recent study reported that treatment of peri-implantitis using PRF was clinically more
      effective than with access flap surgery alone. It was also concluded in the study that PRF
      improves the outcomes of surgical peri-implantitis treatment (Hamzacebi et al. 2015).

      There have been recent developments of various techniques using platelet concentrate to
      provide different rates of platelets, leukocytes, growth factors, stem cells and fibrin
      matrix. Sacco developed concentrated growth factors (CGF) as a therapeutic protocol obtained
      by separating the venous blood centrifuged using a special device in the same manner as PRF
      (Rodella et al. 2011). It was also argued that centrifugation at a different speed provides a
      larger, denser fibrin matrix compared to PRF, which results in improved regenerative capacity
      and greater versatility (Sohn et al. 2009). Some recent studies have reported that CGF
      accelerates new bone formation related to guided bone regeneration (Sohn et al. 2011; Kim et
      al. 2014).

      The purpose of this randomized, controlled clinical study was to evaluate the clinical and
      radiological results of implant surface decontamination using sterile saline alone or in
      combination with ozone therapy applied as surgical regenerative treatment for
      peri-implantitis.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: probing depth of peri-implantitis sites
time frame: 6 months postoperatively
description: measured as the distance between the deepest site of the pocket to the peri-implant mucosal margin
measure: bone loss of peri-implant defects
time frame: 6 months postoperatively
description: Measurements were taken of mesial and distal distances between the first bone to implant contact and bone loss (BL) in the implant shoulder
arm group label: Ozone Group
arm group type: Active Comparator
description: Decontamination of implant surfaces with saline irrigation and additional ozone therapy in combination with regenerative surgery
arm group label: Control Group
arm group type: Active Comparator
description: Decontamination of implant surfaces with saline irrigation alone in combination with regenerative surgery
intervention type: Procedure
intervention name: Decontamination of implant surfaces
description: Decontamination of implant surfaces in combination with regenerative surgery
arm group label: Control Group
arm group label: Ozone Group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Berrin Unsal, PhD
role: Study Director
affiliation: Prof Dr
responsible party type: Principal Investigator
investigator affiliation: Gazi University
investigator full name: Sıla Çağrı İşler
investigator title: PhD
mesh term: Peri-Implantitis
sharing ipd: No