<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/NCT03753464</url>
  </required_header>
  <id_info>
    <org_study_id>18-00986</org_study_id>
    <nct_id>NCT03753464</nct_id>
  </id_info>
  <brief_title>The Role of Functional Epigenetic Modifications in Peri-Implantitis</brief_title>
  <official_title>The Role of Functional Epigenetic Modifications in Peri-Implantitis: A Pilot Clinical Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NYU College of Dentistry</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>NYU College of Dentistry</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>
      The aim of this pilot, exploratory, single blind clinical trial is to evaluate the epigenetic&#xD;
      changes associated with peri-implantitis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Twenty patients will be voluntarily enrolled in two groups: 10 healthy participants, and 10&#xD;
      participants with peri-implantitis. Periodontal and peri-implant clinical and radiographic&#xD;
      measurements, as well as body mass index, medical and dental history will be recorded within&#xD;
      the following timelines: at baseline (for both groups), and 6 months after baseline for the&#xD;
      peri-implantitis group only. At baseline, gingival biopsies and blood will be harvested from:&#xD;
      a) healthy gingival sites during either surgical removal of wisdom teeth or gingivoplasty, in&#xD;
      the healthy group; and, b) from a peri-implantitis site during surgical treatment of&#xD;
      peri-implantitis, and when possible, from a healthy gingival site within the same&#xD;
      participant, in the peri-implantitis group. After harvesting of biopsies, peri-implantitis&#xD;
      subjects will be re-evaluated 6 months after treatment. During the 6-month visit, if a second&#xD;
      surgical treatment of peri-implantitis in the same implant treated at baseline is indicated&#xD;
      as standard of care of the participant, a new gingiva biopsy and blood will be collected.&#xD;
      Gingival biopsies and blood collected from each participant will be used to perform DNA&#xD;
      methylation analysis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">October 1, 2018</start_date>
  <completion_date type="Anticipated">July 2021</completion_date>
  <primary_completion_date type="Anticipated">July 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Differences in epigenetic signatures in peri-implantitis subjects as compared to healthy subjects, in an exploratory manner. (Gingival biopsies and blood collected to perform DNA methylation analysis)</measure>
    <time_frame>6 months</time_frame>
    <description>Gingival and blood samples collected from healthy subjects and subjects with peri-implantitis will be used to determinate epigenetic signatures associated with peri-implantitis.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Epigenetic signatures associated with response to treatment peri-implantitis at 6 months, in an exploratory manner. (Differences in epigenetic signatures in peri-implantitis subjects as compared to healthy subjects, in an exploratory manner.</measure>
    <time_frame>6 months</time_frame>
    <description>Samples collected from patients with peri-implantitis will be used to determinate epigenetic signatures associated response to treatment peri-implantitis at 6 months. (Gingival biopsies and blood collected to perform DNA methylation analysis)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Visual Analog Scale (VAS) will be assessed to determinate patient-reported outcome measures, at baseline and at 6 months.</measure>
    <time_frame>6 months</time_frame>
    <description>A visual analog scale (VAS) will be used to evaluate patient's pain/discomfort, esthetic satisfaction, and the subjects' overall satisfaction at baseline and at 6 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oral Health Impact Profile-14 (OHIP-14) will be assessed to determinate patient-reported outcome measures, at baseline and at 6 months.</measure>
    <time_frame>6 months</time_frame>
    <description>Oral Health Impact Profile-14 (OHIP-14) assessed at baseline and at 6 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in peri-implant pocket depths (PPD) (in mm) from baseline to 6 month after surgery (only peri-implantitis group).</measure>
    <time_frame>6 months</time_frame>
    <description>Peri-implant pocket depths (PPD) will be assessed at baseline and 6 month after surgery.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in peri-implant BOP (in percentage), from baseline to 6 month after surgery (only peri-implantitis group).</measure>
    <time_frame>6 months</time_frame>
    <description>Peri-implant BOP (in percentage) will be assessed at baseline and 6 month after surgery.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of peri-implant pocket closure at to 6 month after surgery (only peri-implantitis group).</measure>
    <time_frame>6 months</time_frame>
    <description>Percentage of peri-implant pocket closure will be assessed at at to 6 month after surgery.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in peri-implant marginal bone level (in mm) from baseline to 6 month after surgery (only peri-implantitis group).</measure>
    <time_frame>6 months</time_frame>
    <description>Mean crestal bone level change around the implants will be determined by periapical radiographs of mesial and distal bone levels from baseline to 6 months surgery.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in soft tissue levels (in mm) from baseline to 6 month after surgery (only peri-implantitis group).</measure>
    <time_frame>6 months</time_frame>
    <description>Soft tissue levels assessed at baseline and 6 months post-surgery in implants with peri-implantitis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of post-operative surgical site infections (only peri-implantitis group).</measure>
    <time_frame>6 months</time_frame>
    <description>Number of post-operative surgical site infections from surgery to 6 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of post-operative complications (only peri-implantitis group).</measure>
    <time_frame>6 months</time_frame>
    <description>Number of post-operative complications from surgery to 6 months.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Periimplantitis</condition>
  <arm_group>
    <arm_group_label>Peri-implantitis</arm_group_label>
    <description>Patients undergoing surgical treatment for peri-implantitis. Gingival and blood samples will be collected during the treatment for peri-implantitis.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy</arm_group_label>
    <description>Healthy patients undergoing treatment for either wisdom tooth extraction or gingivectomy. Gingival and blood samples will be collected during either wisdom tooth extraction or gingivectomy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Gingival biopsy and blood sample collection</intervention_name>
    <description>Gingival and blood samples will be collected.</description>
    <arm_group_label>Healthy</arm_group_label>
    <arm_group_label>Peri-implantitis</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Gingival and blood samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        -  Periodontally Healthy Subjects&#xD;
&#xD;
          -  Peri-implantitis Subjects&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        General Inclusion Criteria:&#xD;
&#xD;
          -  Subjects must have read, understood, and signed an informed consent form.&#xD;
&#xD;
          -  Subjects must be 20-90 years of age.&#xD;
&#xD;
          -  Subjects must be non-smokers or ex-smokers who have quit smoking for at least one year&#xD;
             prior to enrollment in the study.&#xD;
&#xD;
          -  Subjects must be in good general health as assessed by the Investigator.&#xD;
&#xD;
        Healthy Periodontal Subjects Inclusion Criteria:&#xD;
&#xD;
        In addition to the general inclusion criteria, a healthy periodontal subject must meet all&#xD;
        of the following criteria:&#xD;
&#xD;
        • Subjects show gingival health and no history of periodontitis, as described in the 2017&#xD;
        World Workshop on the Classification of Periodontal and Peri-Implant Diseases and&#xD;
        Conditions.&#xD;
&#xD;
        Peri-implantitis Subjects Inclusion Criteria:&#xD;
&#xD;
        In addition to the general inclusion criteria, a PIT subject must meet all of the following&#xD;
        criteria:&#xD;
&#xD;
          -  Subjects with implant-supported prosthesis/es in function for at least 12 months who&#xD;
             had at least one implant diagnosed with peri-implantitis based on the 2017 World&#xD;
             Workshop on the Classification of Periodontal and Peri-Implant Diseases and&#xD;
             Conditions.&#xD;
&#xD;
          -  Subjects must be committed to the study and the required follow-up visits.&#xD;
&#xD;
          -  Standard of care treatment of the diseased implant with PID will consist on open flap&#xD;
             debridement (OFD).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        General Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or lactating.&#xD;
&#xD;
          -  Use of antibiotics, within 1 month before enrollment in the study.&#xD;
&#xD;
          -  Chronic use of nonsteroidal anti-inflammatory drugs for over 3 weeks of continuous use&#xD;
             at the time of enrollment or during the course of the study.&#xD;
&#xD;
          -  Requirement for prophylactic antibiotics for dental procedures.&#xD;
&#xD;
          -  Mucosal diseases in the localized area around the biopsy site.&#xD;
&#xD;
          -  Subjects with a systemic disease that would preclude biopsy/oral surgery.&#xD;
&#xD;
          -  History of local irradiation therapy in the head/neck area.&#xD;
&#xD;
          -  Subjects with poor oral hygiene.&#xD;
&#xD;
          -  Subjects receiving, or having a history of receiving intravenous or subcutaneous&#xD;
             anti-resorptive agents associated with osteonecrosis of the jaw.&#xD;
&#xD;
          -  Subjects with any untreated endodontic lesions or untreated periodontal disease&#xD;
             adjacent to the biopsy site.&#xD;
&#xD;
          -  Acute necrotizing ulcerative gingivitis or gross tooth decay, as determined by the&#xD;
             investigator.&#xD;
&#xD;
          -  Subjects with conditions or circumstances, in the opinion of the investigator, which&#xD;
             would prevent completion of study participation or interfere with analysis.&#xD;
&#xD;
        Periodontally Healthy Subjects Exclusion:&#xD;
&#xD;
        In addition to the general exclusion criteria, subjects allocated to the healthy group who&#xD;
        meet any of the following criteria will be excluded from participation in this study:&#xD;
&#xD;
        • Root fragments, pericoronitis, endo-perio lesions, gross tooth decay, or other dental&#xD;
        abscesses at the biopsy site. Subjects may be rescreened after resolution of these dental&#xD;
        conditions.&#xD;
&#xD;
        Peri-implantitis subjects Exclusion:&#xD;
&#xD;
        In addition to the general exclusion criteria, subjects allocated to the PIT group who meet&#xD;
        any of the following criteria will be excluded from participation in this study:&#xD;
&#xD;
          -  Inadequate implant position (i.e., prosthetically driven).&#xD;
&#xD;
          -  PIT due to excess of cement.&#xD;
&#xD;
          -  Subjects who have physical or mental handicaps that would interfere with the ability&#xD;
             to perform adequate oral hygiene.&#xD;
&#xD;
          -  Subjects with implants previously surgically treated for PIT.&#xD;
&#xD;
          -  Less than 2mm of keratinized peri-implant tissue.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ismael Khouly, DDS, MS, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>New York University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Bluestone Center for Clinical Research. New York University College of Dentistry</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10010-4086</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>November 15, 2018</study_first_submitted>
  <study_first_submitted_qc>November 26, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 27, 2018</study_first_posted>
  <last_update_submitted>March 6, 2021</last_update_submitted>
  <last_update_submitted_qc>March 6, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 9, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>NYU College of Dentistry</investigator_affiliation>
    <investigator_full_name>Ismael Khouly</investigator_full_name>
    <investigator_title>Clinical Assistant Professor, Department of Oral &amp; Maxillofacial Surgery</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Peri-Implantitis</mesh_term>
  </condition_browse>
  <!-- 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/NCT03753464
org study id: 18-00986
nct id: NCT03753464
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The aim of this pilot, exploratory, single blind clinical trial is to evaluate the epigenetic
      changes associated with peri-implantitis.
Twenty patients will be voluntarily enrolled in two groups: 10 healthy participants, and 10
      participants with peri-implantitis. Periodontal and peri-implant clinical and radiographic
      measurements, as well as body mass index, medical and dental history will be recorded within
      the following timelines: at baseline (for both groups), and 6 months after baseline for the
      peri-implantitis group only. At baseline, gingival biopsies and blood will be harvested from:
      a) healthy gingival sites during either surgical removal of wisdom teeth or gingivoplasty, in
      the healthy group; and, b) from a peri-implantitis site during surgical treatment of
      peri-implantitis, and when possible, from a healthy gingival site within the same
      participant, in the peri-implantitis group. After harvesting of biopsies, peri-implantitis
      subjects will be re-evaluated 6 months after treatment. During the 6-month visit, if a second
      surgical treatment of peri-implantitis in the same implant treated at baseline is indicated
      as standard of care of the participant, a new gingiva biopsy and blood will be collected.
      Gingival biopsies and blood collected from each participant will be used to perform DNA
      methylation analysis.
observational model: Case-Control
time perspective: Prospective
measure: Differences in epigenetic signatures in peri-implantitis subjects as compared to healthy subjects, in an exploratory manner. (Gingival biopsies and blood collected to perform DNA methylation analysis)
time frame: 6 months
description: Gingival and blood samples collected from healthy subjects and subjects with peri-implantitis will be used to determinate epigenetic signatures associated with peri-implantitis.
measure: Epigenetic signatures associated with response to treatment peri-implantitis at 6 months, in an exploratory manner. (Differences in epigenetic signatures in peri-implantitis subjects as compared to healthy subjects, in an exploratory manner.
time frame: 6 months
description: Samples collected from patients with peri-implantitis will be used to determinate epigenetic signatures associated response to treatment peri-implantitis at 6 months. (Gingival biopsies and blood collected to perform DNA methylation analysis)
measure: Visual Analog Scale (VAS) will be assessed to determinate patient-reported outcome measures, at baseline and at 6 months.
time frame: 6 months
description: A visual analog scale (VAS) will be used to evaluate patient's pain/discomfort, esthetic satisfaction, and the subjects' overall satisfaction at baseline and at 6 months.
measure: Oral Health Impact Profile-14 (OHIP-14) will be assessed to determinate patient-reported outcome measures, at baseline and at 6 months.
time frame: 6 months
description: Oral Health Impact Profile-14 (OHIP-14) assessed at baseline and at 6 months.
measure: Changes in peri-implant pocket depths (PPD) (in mm) from baseline to 6 month after surgery (only peri-implantitis group).
time frame: 6 months
description: Peri-implant pocket depths (PPD) will be assessed at baseline and 6 month after surgery.
measure: Changes in peri-implant BOP (in percentage), from baseline to 6 month after surgery (only peri-implantitis group).
time frame: 6 months
description: Peri-implant BOP (in percentage) will be assessed at baseline and 6 month after surgery.
measure: Percentage of peri-implant pocket closure at to 6 month after surgery (only peri-implantitis group).
time frame: 6 months
description: Percentage of peri-implant pocket closure will be assessed at at to 6 month after surgery.
measure: Changes in peri-implant marginal bone level (in mm) from baseline to 6 month after surgery (only peri-implantitis group).
time frame: 6 months
description: Mean crestal bone level change around the implants will be determined by periapical radiographs of mesial and distal bone levels from baseline to 6 months surgery.
measure: Change in soft tissue levels (in mm) from baseline to 6 month after surgery (only peri-implantitis group).
time frame: 6 months
description: Soft tissue levels assessed at baseline and 6 months post-surgery in implants with peri-implantitis.
measure: Incidence of post-operative surgical site infections (only peri-implantitis group).
time frame: 6 months
description: Number of post-operative surgical site infections from surgery to 6 months.
measure: Incidence of post-operative complications (only peri-implantitis group).
time frame: 6 months
description: Number of post-operative complications from surgery to 6 months.
arm group label: Peri-implantitis
description: Patients undergoing surgical treatment for peri-implantitis. Gingival and blood samples will be collected during the treatment for peri-implantitis.
arm group label: Healthy
description: Healthy patients undergoing treatment for either wisdom tooth extraction or gingivectomy. Gingival and blood samples will be collected during either wisdom tooth extraction or gingivectomy.
intervention type: Procedure
intervention name: Gingival biopsy and blood sample collection
description: Gingival and blood samples will be collected.
arm group label: Healthy
arm group label: Peri-implantitis
Gingival and blood samples
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 20 Years
maximum age: 90 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ismael Khouly, DDS, MS, PhD
role: Principal Investigator
affiliation: New York University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: NYU College of Dentistry
investigator full name: Ismael Khouly
investigator title: Clinical Assistant Professor, Department of Oral & Maxillofacial Surgery
mesh term: Peri-Implantitis