<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/NCT04436939</url>
  </required_header>
  <id_info>
    <org_study_id>22101980.1</org_study_id>
    <nct_id>NCT04436939</nct_id>
  </id_info>
  <brief_title>Soft Tissue Response to Peek and Ti Healing Abutments</brief_title>
  <official_title>Soft Tissue Response to Polyetheretherketone (PEEK) and Titanium (Ti) Healing Abutments on Dental Implants</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Belgrade</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Belgrade</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Introduction: Single-stage dental implant placement protocol involves the placement of&#xD;
      healing abutments. In addition to osseointegration process, healing of peri-implant soft&#xD;
      tissues is of a great importance too. Routinely, healing abutments made of titanium (Ti) are&#xD;
      used. The aim is to find novel materials that would have the same mechanical properties, but&#xD;
      less prone to plaque-adhesion and therefore showing lower local inflammatory soft tissue&#xD;
      response. Polyetheretherketone (PEEK) is a thermoplastic polymer that has favorable&#xD;
      mechanical characteristics, high biocompatibility and low submissiveness to microorganism&#xD;
      adhesion. White color makes it aesthetically acceptable in the treatment of patients with&#xD;
      thin gingival phenotype.&#xD;
&#xD;
      The Aim: To compare the formation of dental plaque on PEEK and Ti healing abutments and&#xD;
      examine the local response of peri-implant tissues.&#xD;
&#xD;
      Materials and Methods: The study included 11 patients with at least two missing teeth in the&#xD;
      posterior regions. In each patient, 2 implants were installed, with PEEK abutment&#xD;
      (experimental group) placed on one implant, while on the other implant, Ti abutment (control&#xD;
      group) was placed. Before prosthetic rehabilitation of patients, both abutments were replaced&#xD;
      with new ones and a thin layer of peri-implant soft tissue was sent to histological analysis.&#xD;
&#xD;
      Results: The average age of patients was 49 years. Out of 11 patients, 27% were female and&#xD;
      73% male. 36% of respondents were smokers. Histological immunohistochemical analysis of&#xD;
      samples of peri-implant soft tissues showed massive inflammatory infiltration in&#xD;
      subepithelial tissue in the experimental group (10/11), while the inflammatory infiltrate in&#xD;
      the control group was classified as moderate (7/11) or weak (4/11).&#xD;
&#xD;
      Conclusion: Both types of healing abutments have been shown to be successful in single-stage&#xD;
      implantation protocol. However, contrary to expectations and preliminary findings from the&#xD;
      literature, PEEK healing abutments showed a more pronounced inflammatory response of the&#xD;
      surrounding soft tissues relative to Titanium abutments.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study design This study was performed at Department of Periodontology and Oral medicine of&#xD;
      the Belgrade School of Dental Medicine in collaboration with the Institute of Pathology of&#xD;
      the Belgrade School of Medicine. The study was approved by the Institutional Ethical&#xD;
      Committee and all subjects enrolled in this trial have signed an informed consent according&#xD;
      to the Helsinki declaration of 1964 and subsequent amendments. It was a randomized clinical&#xD;
      trial, with a split mouth design, in which each subject served as both experimental and&#xD;
      control group.&#xD;
&#xD;
      Study sample The subjects included in this study are patients of the Department of&#xD;
      Periodontology and Oral Medicine, School of Dental Medicine, University of Belgrade.&#xD;
      Individuals diagnosed with partial edentulism in posterior maxillary or mandibular arches,&#xD;
      with missing at least two teeth that were extracted at least 6 months earlier, have been&#xD;
      selected following clinical and radiological examination.&#xD;
&#xD;
      Ten patients with indication for implant placement (presenting bilateral single tooth gaps&#xD;
      and/or extended edentulous spaces distally from maxillary or mandibular canines) were&#xD;
      included in this study if they fulfilled the following criteria:&#xD;
&#xD;
        1. Men and non-pregnant women, 18 to 70 years of age;&#xD;
&#xD;
        2. Systemically healthy patients&#xD;
&#xD;
        3. Adequate bone quantity at the experimental sites to allow the insertion of 3.8 or 4.3 mm&#xD;
           diameter implants&#xD;
&#xD;
        4. Sufficient band of keratinized mucosa at the experimental sites&#xD;
&#xD;
        5. No active periodontal disease at the time of inclusion/surgery and proper oral hygiene&#xD;
           defined by bleeding on probing scores (BOP) and plaque indices (PI) less then 15%&#xD;
&#xD;
      Titanium implants placed in the posterior mandible and maxilla were randomly assigned to&#xD;
      receive transmucosal healing by either: PEEK healing abutment (A, experimental group) or Ti&#xD;
      healing abutment (B, control group). Randomization was performed by a toss of a coin.&#xD;
&#xD;
      Surgical procedures&#xD;
&#xD;
      Implant placement was carried out under local anesthesia (2% lidocaine with epinephrine,&#xD;
      1:100000). Mid-crestal incisions were made and mucoperiosteal flaps (MPFs) were elevated not&#xD;
      to interfere with muco-gingival junction. Surgical implant sites were prepared according to a&#xD;
      standard procedure using a low-trauma surgical technique under copious irrigation with&#xD;
      sterile 0.9% physiological saline. Thereafter, two bone level implants were inserted (C-TECH&#xD;
      Esthetic line (EL), Italy) in 1mm subcrestally, in a one-stage protocol. The diameter and&#xD;
      length of the implant were chosen following CBCT data analysis. Study abutments (C-TECH,&#xD;
      Italy) were provided in width of 4 mm and in different heights (2, 3, 4 mm). In the&#xD;
      experimental group, immediately following implant placement, a PEEK abutment was screwed at&#xD;
      10 Ncm, while in the control group, the same procedure was performed by means of TI healing&#xD;
      abutment.&#xD;
&#xD;
      All abutments were connected using a torque of 10 Ncm. Subsequently, the MPFs were&#xD;
      repositioned and adapted using non-resorbable single sutures to ensure a transmucosal healing&#xD;
      procedure.&#xD;
&#xD;
      Postoperative Care&#xD;
&#xD;
      Patients were prescribed antimicrobials (Amoxicillin caps. 500mg, 3x1 or Clindamycin, 600mg,&#xD;
      2x1, for patients allergic to penicillin), analgesics (Ibuprofen, 600 mg, every 6 hours) and&#xD;
      0.2% chlorhexidine solution (ASD Curasept 212, Curaden, Switzerland). Sutures were removed&#xD;
      one week after the surgery.&#xD;
&#xD;
      Sampling 3 months following the implant surgery, a minimally invasive surgical procedure was&#xD;
      performed for the placement of larger diameter (5mm wide) healing abutments. At this stage, a&#xD;
      triangular incision was performed at mesial and distal aspect of the existing implant healing&#xD;
      abutment, to remove both the healing abutment with the band of the surrounding soft tissue of&#xD;
      1-1.5mm in thickness.&#xD;
&#xD;
      Soft tissue specimens were gently rinsed with 4% formalin and fixed in 4% neutral buffered&#xD;
      formalin solution. The samples were processed to the laboratory for further histological&#xD;
      preparation.&#xD;
&#xD;
      Finally, commercially available 5 mm wide healing abutments (C-TECH) were selected by height&#xD;
      according to the individual situation and applied to ensure a conditioning of the soft&#xD;
      tissues prior to prosthetic restauration.&#xD;
&#xD;
      Light microscopic analysis Analysis was performed by two independent observer-pathologists,&#xD;
      blinded to the treatment, samples marked as patients from group A and B. For microscopic&#xD;
      histological evaluation, biopsy were fixed in 10% neutral-buffered formalin. Three 5-μm-thick&#xD;
      paraffin-embedded horizontal sections were cut dyed with a haematoxylin-eosin (HE) stain and&#xD;
      analyzed by light microscopy and microscope Nikon Eclipse Ci with control unit DS-L3 and&#xD;
      pre-installed software. Following morphological changes were analyzed: presence, localization&#xD;
      and intensity of the inflammation. Presence in epithelial and subepithelial tissue were&#xD;
      categorized qualitatively (yes/no) and intensity semiqualitatively (light, medium,&#xD;
      intensive).&#xD;
&#xD;
      For immunohistochemical analysis serial sections, 5 µm thick, were cut and&#xD;
      immunohistochemical techniques were carried out using the avidin-biotin-peroxidase complex&#xD;
      method with an LSAB2 kit (Dako, Glostrup, Denmark). The primary antibodies used in this study&#xD;
      were: LCA (M3629Clone 318-6-11, dilution 1 : 25; Dako), CD 3 (M3539 Clone β-catenin1,&#xD;
      dilution 1 : 200; Dako), CD 20 (M7240 Clone MIB-1, dilution 1 : 100; Dako), and CD 68&#xD;
      (EPR2241, ab134175, dilution 1 : 200; Abcam).&#xD;
&#xD;
      Cells with cytoplasmic staining were considered positive in immunohistochemistry for all&#xD;
      antibodies. The labeled-cell count of all antibodies was determined in ten high-power fields&#xD;
      at 200× magnification.&#xD;
&#xD;
      In statistics, uni- and multivariate analyses were used, and a p-value of less than 0.05 was&#xD;
      accepted as statistically significant.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 1, 2018</start_date>
  <completion_date type="Actual">February 12, 2019</completion_date>
  <primary_completion_date type="Actual">December 3, 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>Parallel Assignment</intervention_model>
    <intervention_model_description>This was a split mouth study design in which both test and control group were the same patient</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Soft tissue inflammatory reaction around healing abutments</measure>
    <time_frame>Three month after the implant placement</time_frame>
    <description>For microscopic histological evaluation, soft tissue biopsies were prepared, dyed with a haematoxylin-eosin stain and analyzed by light microscopy for presence, localization and intensity of the inflammation.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Dental Implants</condition>
  <arm_group>
    <arm_group_label>PEEK healing abutment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healing abutment made of polyetheretherketone (PEEK)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ti healing abutment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Healing abutment made of titanium (Ti)</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Dental implant</intervention_name>
    <description>Following dental implant installation, PEEK or Ti healing abutments were placed according to the split mouth study design.</description>
    <arm_group_label>PEEK healing abutment</arm_group_label>
    <arm_group_label>Ti healing abutment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Individuals diagnosed with partial edentulism in posterior maxillary or mandibular&#xD;
             arches, with missing at least two teeth that were extracted at least 6 months earlier&#xD;
&#xD;
          -  Adequate bone quantity at the experimental sites to allow the insertion of 3.8 or 4.3&#xD;
             mm diameter implants&#xD;
&#xD;
          -  Sufficient band of keratinized mucosa at the experimental sites&#xD;
&#xD;
          -  No active periodontal disease at the time of inclusion/surgery and proper oral hygiene&#xD;
             defined by bleeding on probing scores (BOP) and plaque indices (PI) less then 15%&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        -&#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>Zoran M Aleksic, DDS, MS, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Department of Periodontology, Belgrade School of Dental Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Periodontology, School of Dental Medicine, University of Belgrade</name>
      <address>
        <city>Belgrade</city>
        <zip>11000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Serbia</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 16, 2020</study_first_submitted>
  <study_first_submitted_qc>June 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 18, 2020</study_first_posted>
  <last_update_submitted>June 22, 2020</last_update_submitted>
  <last_update_submitted_qc>June 22, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 24, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Belgrade</investigator_affiliation>
    <investigator_full_name>Iva Milinkovic</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>dental implant</keyword>
  <keyword>healing abutment</keyword>
  <keyword>PEEK</keyword>
  <keyword>Titanium</keyword>
  <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/NCT04436939
org study id: 22101980.1
nct id: NCT04436939
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Introduction: Single-stage dental implant placement protocol involves the placement of
      healing abutments. In addition to osseointegration process, healing of peri-implant soft
      tissues is of a great importance too. Routinely, healing abutments made of titanium (Ti) are
      used. The aim is to find novel materials that would have the same mechanical properties, but
      less prone to plaque-adhesion and therefore showing lower local inflammatory soft tissue
      response. Polyetheretherketone (PEEK) is a thermoplastic polymer that has favorable
      mechanical characteristics, high biocompatibility and low submissiveness to microorganism
      adhesion. White color makes it aesthetically acceptable in the treatment of patients with
      thin gingival phenotype.

      The Aim: To compare the formation of dental plaque on PEEK and Ti healing abutments and
      examine the local response of peri-implant tissues.

      Materials and Methods: The study included 11 patients with at least two missing teeth in the
      posterior regions. In each patient, 2 implants were installed, with PEEK abutment
      (experimental group) placed on one implant, while on the other implant, Ti abutment (control
      group) was placed. Before prosthetic rehabilitation of patients, both abutments were replaced
      with new ones and a thin layer of peri-implant soft tissue was sent to histological analysis.

      Results: The average age of patients was 49 years. Out of 11 patients, 27% were female and
      73% male. 36% of respondents were smokers. Histological immunohistochemical analysis of
      samples of peri-implant soft tissues showed massive inflammatory infiltration in
      subepithelial tissue in the experimental group (10/11), while the inflammatory infiltrate in
      the control group was classified as moderate (7/11) or weak (4/11).

      Conclusion: Both types of healing abutments have been shown to be successful in single-stage
      implantation protocol. However, contrary to expectations and preliminary findings from the
      literature, PEEK healing abutments showed a more pronounced inflammatory response of the
      surrounding soft tissues relative to Titanium abutments.
Study design This study was performed at Department of Periodontology and Oral medicine of
      the Belgrade School of Dental Medicine in collaboration with the Institute of Pathology of
      the Belgrade School of Medicine. The study was approved by the Institutional Ethical
      Committee and all subjects enrolled in this trial have signed an informed consent according
      to the Helsinki declaration of 1964 and subsequent amendments. It was a randomized clinical
      trial, with a split mouth design, in which each subject served as both experimental and
      control group.

      Study sample The subjects included in this study are patients of the Department of
      Periodontology and Oral Medicine, School of Dental Medicine, University of Belgrade.
      Individuals diagnosed with partial edentulism in posterior maxillary or mandibular arches,
      with missing at least two teeth that were extracted at least 6 months earlier, have been
      selected following clinical and radiological examination.

      Ten patients with indication for implant placement (presenting bilateral single tooth gaps
      and/or extended edentulous spaces distally from maxillary or mandibular canines) were
      included in this study if they fulfilled the following criteria:

        1. Men and non-pregnant women, 18 to 70 years of age;

        2. Systemically healthy patients

        3. Adequate bone quantity at the experimental sites to allow the insertion of 3.8 or 4.3 mm
           diameter implants

        4. Sufficient band of keratinized mucosa at the experimental sites

        5. No active periodontal disease at the time of inclusion/surgery and proper oral hygiene
           defined by bleeding on probing scores (BOP) and plaque indices (PI) less then 15%

      Titanium implants placed in the posterior mandible and maxilla were randomly assigned to
      receive transmucosal healing by either: PEEK healing abutment (A, experimental group) or Ti
      healing abutment (B, control group). Randomization was performed by a toss of a coin.

      Surgical procedures

      Implant placement was carried out under local anesthesia (2% lidocaine with epinephrine,
      1:100000). Mid-crestal incisions were made and mucoperiosteal flaps (MPFs) were elevated not
      to interfere with muco-gingival junction. Surgical implant sites were prepared according to a
      standard procedure using a low-trauma surgical technique under copious irrigation with
      sterile 0.9% physiological saline. Thereafter, two bone level implants were inserted (C-TECH
      Esthetic line (EL), Italy) in 1mm subcrestally, in a one-stage protocol. The diameter and
      length of the implant were chosen following CBCT data analysis. Study abutments (C-TECH,
      Italy) were provided in width of 4 mm and in different heights (2, 3, 4 mm). In the
      experimental group, immediately following implant placement, a PEEK abutment was screwed at
      10 Ncm, while in the control group, the same procedure was performed by means of TI healing
      abutment.

      All abutments were connected using a torque of 10 Ncm. Subsequently, the MPFs were
      repositioned and adapted using non-resorbable single sutures to ensure a transmucosal healing
      procedure.

      Postoperative Care

      Patients were prescribed antimicrobials (Amoxicillin caps. 500mg, 3x1 or Clindamycin, 600mg,
      2x1, for patients allergic to penicillin), analgesics (Ibuprofen, 600 mg, every 6 hours) and
      0.2% chlorhexidine solution (ASD Curasept 212, Curaden, Switzerland). Sutures were removed
      one week after the surgery.

      Sampling 3 months following the implant surgery, a minimally invasive surgical procedure was
      performed for the placement of larger diameter (5mm wide) healing abutments. At this stage, a
      triangular incision was performed at mesial and distal aspect of the existing implant healing
      abutment, to remove both the healing abutment with the band of the surrounding soft tissue of
      1-1.5mm in thickness.

      Soft tissue specimens were gently rinsed with 4% formalin and fixed in 4% neutral buffered
      formalin solution. The samples were processed to the laboratory for further histological
      preparation.

      Finally, commercially available 5 mm wide healing abutments (C-TECH) were selected by height
      according to the individual situation and applied to ensure a conditioning of the soft
      tissues prior to prosthetic restauration.

      Light microscopic analysis Analysis was performed by two independent observer-pathologists,
      blinded to the treatment, samples marked as patients from group A and B. For microscopic
      histological evaluation, biopsy were fixed in 10% neutral-buffered formalin. Three 5-μm-thick
      paraffin-embedded horizontal sections were cut dyed with a haematoxylin-eosin (HE) stain and
      analyzed by light microscopy and microscope Nikon Eclipse Ci with control unit DS-L3 and
      pre-installed software. Following morphological changes were analyzed: presence, localization
      and intensity of the inflammation. Presence in epithelial and subepithelial tissue were
      categorized qualitatively (yes/no) and intensity semiqualitatively (light, medium,
      intensive).

      For immunohistochemical analysis serial sections, 5 µm thick, were cut and
      immunohistochemical techniques were carried out using the avidin-biotin-peroxidase complex
      method with an LSAB2 kit (Dako, Glostrup, Denmark). The primary antibodies used in this study
      were: LCA (M3629Clone 318-6-11, dilution 1 : 25; Dako), CD 3 (M3539 Clone β-catenin1,
      dilution 1 : 200; Dako), CD 20 (M7240 Clone MIB-1, dilution 1 : 100; Dako), and CD 68
      (EPR2241, ab134175, dilution 1 : 200; Abcam).

      Cells with cytoplasmic staining were considered positive in immunohistochemistry for all
      antibodies. The labeled-cell count of all antibodies was determined in ten high-power fields
      at 200× magnification.

      In statistics, uni- and multivariate analyses were used, and a p-value of less than 0.05 was
      accepted as statistically significant.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This was a split mouth study design in which both test and control group were the same patient
primary purpose: Basic Science
masking: None (Open Label)
measure: Soft tissue inflammatory reaction around healing abutments
time frame: Three month after the implant placement
description: For microscopic histological evaluation, soft tissue biopsies were prepared, dyed with a haematoxylin-eosin stain and analyzed by light microscopy for presence, localization and intensity of the inflammation.
arm group label: PEEK healing abutment
arm group type: Experimental
description: Healing abutment made of polyetheretherketone (PEEK)
arm group label: Ti healing abutment
arm group type: Active Comparator
description: Healing abutment made of titanium (Ti)
intervention type: Device
intervention name: Dental implant
description: Following dental implant installation, PEEK or Ti healing abutments were placed according to the split mouth study design.
arm group label: PEEK healing abutment
arm group label: Ti healing abutment
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Zoran M Aleksic, DDS, MS, PhD
role: Study Director
affiliation: Department of Periodontology, Belgrade School of Dental Medicine
facility: 
country: Serbia
responsible party type: Principal Investigator
investigator affiliation: University of Belgrade
investigator full name: Iva Milinkovic
investigator title: Assistant Professor
sharing ipd: No