<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/NCT03753451</url>
  </required_header>
  <id_info>
    <org_study_id>SDC 4329/15/156</org_study_id>
    <nct_id>NCT03753451</nct_id>
  </id_info>
  <brief_title>Influence of Periodontal Disease Treatment on Serum Levels of Sirtuin 1 and Mannose-binding Lectin</brief_title>
  <official_title>Influence of Periodontal Disease Treatment on Serum Levels of Sirtuin 1 and Mannose-binding Lectin in Individuals With Coronary Artery Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>InCor Heart Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>InCor Heart Institute</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>
      The premise of the relationship between the atherosclerotic process of coronary artery&#xD;
      disease and periodontal disease is the immunoinflammatory process, which causes a significant&#xD;
      increase in serum concentration of mannose-binding lectin. This protein is part of the innate&#xD;
      immunity and has the ability to bind to the mannose residues common to various pathogens.&#xD;
      Animal studies also showed that increased serum concentration of sirtuin-1 was associated&#xD;
      with reduced inflammation. Evidence indicates that sirtuin-1 plays an important role in&#xD;
      vascular protection and is associated with aging. OBJECTIVES: This study examined the&#xD;
      influence of non-surgical treatment of periodontal disease on the serum concentration of&#xD;
      mannose-binding lectin and sirtuin-1 in patients with periodontal disease and coronary artery&#xD;
      disease. METHODS: Seventy-eight patients, 38 women and 40 men, mean age 58 ± 8 years old,&#xD;
      were divided into 4 groups: 20 healthy subjects (group 1), 18 patients with coronary artery&#xD;
      disease and without periodontal disease (group 2), 20 patients with periodontal disease and&#xD;
      without coronary artery disease (group 3) and 20 patients with coronary artery disease and&#xD;
      periodontal disease (group 4). Peripheral blood samples were collected at the beginning and&#xD;
      at the end of the treatment of periodontal disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Inclusion criteria for PD were: presence of at least 15 teeth and clinical diagnosis of PD.&#xD;
      Excluding third molars. This diagnosis was confirmed by the presence of at least 6 teeth with&#xD;
      at least one noncontiguous interproximal site with Probing Pocket Depth (PPD) and Clinical&#xD;
      Attachment Loss (CAL) ≥ 5 mm, as well as 30% of Sites with PPD and CAL ≥ 4mm and bleeding on&#xD;
      Probing (BOP). Periodontal disease currently classified as Stage III Degree B. Periodontal&#xD;
      healthy was defined as individuals who presented a periodontium without loss of insertion,&#xD;
      with PPD ≤3 mm, BOP in less than 10% of the sites and without radiographic bone loss.&#xD;
&#xD;
      Non-surgical periodontal treatment was performed, including oral hygiene education, scaling,&#xD;
      smoothing and coronal-radicular polishing (RAR). Six sites were evaluated in each tooth&#xD;
      (mesiobuccal, buccal, distobuccal, distolingual/palatal, lingual/palatal and&#xD;
      mesiolingual/palatal surfaces). Scaling and root planing were performed using mechanical&#xD;
      devices - ultrasound and manual instruments. The treatment was with local anesthesia, 3%&#xD;
      lidocaine with vasoconstrictor, for PPD ≥ 5 mm. The objective of each session was to achieve&#xD;
      a smooth surface, devoid of biofilm and calculus.&#xD;
&#xD;
      The following parameters are evaluated during clinical examination: Probing Pocket Depth&#xD;
      (PPD), distance of the enamel-cementum line at the gingival margin, clinical Attachment Loss&#xD;
      (CAL), plaque index (IP) and bleeding on probing (BOP), PPD and CAL measurements are rounded&#xD;
      to the nearest millimeter using a North Carolina periodontal probe (Chicago, USA).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 1, 2016</start_date>
  <completion_date type="Actual">October 1, 2018</completion_date>
  <primary_completion_date type="Actual">October 1, 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>After improving the periodontal clinical aspects, we observed whether there was an impact on serum levels of mannose-binding lectin (MBL) protein.</measure>
    <time_frame>The periodontal treatment was performed and at the end of three-month period blood sample was collected.</time_frame>
    <description>Non-surgical periodontal treatment was performed to treat the periodontal disease and it included oral hygiene education, scaling, smoothing and polishing of the root and dental crown (RAR). Blood sample was collected at baseline and at the end of study.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>After improving the periodontal clinical aspects, we observed whether there was an impact on serum levels of sirtuin-1 (SIRT1) protein.</measure>
    <time_frame>The periodontal treatment was performed and at the end of three-month period blood sample was collected.</time_frame>
    <description>Non-surgical periodontal treatment was performed to treat the periodontal disease and it included oral hygiene education, scaling, smoothing and polishing of the root and dental crown (RAR). Blood sample was collected at baseline and at the end of study.</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">80</enrollment>
  <condition>Periodontal Diseases</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>20 patients without periodontal disease and coronary artery disease</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>20 patients without periodontal disease and with coronary artery disease</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>20 patients with periodontal disease and with coronary artery disease received treatment of periodontal disease</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 4</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>20 patients with periodontal disease and without coronary artery disease received treatment of periodontal disease</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>treatment of periodontal disease</intervention_name>
    <description>Patients with periodontal disease received treatment of periodontal disease through ultrasound or manual scaling of dental calculations. In addition to receiving instructions to improve oral health, such as the correct use of dental floss, adequate time and the correct way to brush.</description>
    <arm_group_label>Group 3</arm_group_label>
    <arm_group_label>Group 4</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Presence of installed periodontal disease.&#xD;
&#xD;
          -  More than 15 teeth in the mouth&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  uncontrolled diabetic,&#xD;
&#xD;
          -  dialytic,&#xD;
&#xD;
          -  smokers,&#xD;
&#xD;
          -  patients with HIV and Hepatitis B and C.&#xD;
&#xD;
          -  Pregnant subjects,&#xD;
&#xD;
          -  edentulous patients,&#xD;
&#xD;
          -  orthodontic brachytherapy were excluded from the study,&#xD;
&#xD;
          -  patients using specific drugs known to affect periodontal tissues,&#xD;
&#xD;
          -  patients who have undergone previous periodontal treatment (minimum of 6 months), *&#xD;
             patients taking anti-inflammatory drugs and corticosteroids.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Antonio P Mansur, 1</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universidade de São Paulo, São Paulo, SP, BR</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>INCOR- Heart Institute</name>
      <address>
        <city>Sao Paulo</city>
        <state>São Paulo</state>
        <zip>05403900</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>INCOR - Heart Institute</name>
      <address>
        <city>São Paulo</city>
        <zip>05403-900</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <results_reference>
    <citation>Mansur AP, Roggerio A, Goes MFS, Avakian SD, Leal DP, Maranhao RC, Strunz CMC. Serum concentrations and gene expression of sirtuin 1 in healthy and slightly overweight subjects after caloric restriction or resveratrol supplementation: A randomized trial. Int J Cardiol. 2017 Jan 15;227:788-794. doi: 10.1016/j.ijcard.2016.10.058. Epub 2016 Oct 27.</citation>
    <PMID>28029409</PMID>
  </results_reference>
  <results_reference>
    <citation>Liukkonen A, He Q, Gursoy UK, Pussinen PJ, Grondahl-Yli-Hannuksela K, Liukkonen J, Sorsa T, Suominen AL, Huumonen S, Kononen E. Mannose-binding lectin gene polymorphism in relation to periodontal infection. J Periodontal Res. 2017 Jun;52(3):540-545. doi: 10.1111/jre.12420. Epub 2016 Sep 14.</citation>
    <PMID>27624657</PMID>
  </results_reference>
  <results_reference>
    <citation>Tsutsumi A, Kobayashi T, Ito S, Goto D, Matsumoto I, Yoshie H, Sumida T. Mannose binding lectin gene polymorphism and the severity of chronic periodontitis. Nihon Rinsho Meneki Gakkai Kaishi. 2009 Feb;32(1):48-52. doi: 10.2177/jsci.32.48.</citation>
    <PMID>19252378</PMID>
  </results_reference>
  <results_reference>
    <citation>Louropoulou A, van der Velden U, Schoenmaker T, Catsburg A, Savelkoul PH, Loos BG. Mannose-binding lectin gene polymorphisms in relation to periodontitis. J Clin Periodontol. 2008 Nov;35(11):923-30. doi: 10.1111/j.1600-051X.2008.01311.x. Epub 2008 Sep 20.</citation>
    <PMID>18823346</PMID>
  </results_reference>
  <results_reference>
    <citation>Mattagajasingh I, Kim CS, Naqvi A, Yamamori T, Hoffman TA, Jung SB, DeRicco J, Kasuno K, Irani K. SIRT1 promotes endothelium-dependent vascular relaxation by activating endothelial nitric oxide synthase. Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14855-60. doi: 10.1073/pnas.0704329104. Epub 2007 Sep 4.</citation>
    <PMID>17785417</PMID>
  </results_reference>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>November 6, 2018</study_first_submitted>
  <study_first_submitted_qc>November 21, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 27, 2018</study_first_posted>
  <last_update_submitted>November 21, 2018</last_update_submitted>
  <last_update_submitted_qc>November 21, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 27, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>InCor Heart Institute</investigator_affiliation>
    <investigator_full_name>ANTONIO DE PADUA MANSUR</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>periodontal diseases</keyword>
  <keyword>atherosclerosis</keyword>
  <keyword>mannose binding protein</keyword>
  <keyword>sirtuins</keyword>
  <keyword>inflammation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Periodontal Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 15, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/51/NCT03753451/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>October 6, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/51/NCT03753451/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <pending_results>
    <submitted>December 4, 2018</submitted>
    <returned>March 15, 2019</returned>
    <submitted>July 12, 2020</submitted>
    <returned>July 29, 2020</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03753451
org study id: SDC 4329/15/156
nct id: NCT03753451
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The premise of the relationship between the atherosclerotic process of coronary artery
      disease and periodontal disease is the immunoinflammatory process, which causes a significant
      increase in serum concentration of mannose-binding lectin. This protein is part of the innate
      immunity and has the ability to bind to the mannose residues common to various pathogens.
      Animal studies also showed that increased serum concentration of sirtuin-1 was associated
      with reduced inflammation. Evidence indicates that sirtuin-1 plays an important role in
      vascular protection and is associated with aging. OBJECTIVES: This study examined the
      influence of non-surgical treatment of periodontal disease on the serum concentration of
      mannose-binding lectin and sirtuin-1 in patients with periodontal disease and coronary artery
      disease. METHODS: Seventy-eight patients, 38 women and 40 men, mean age 58 ± 8 years old,
      were divided into 4 groups: 20 healthy subjects (group 1), 18 patients with coronary artery
      disease and without periodontal disease (group 2), 20 patients with periodontal disease and
      without coronary artery disease (group 3) and 20 patients with coronary artery disease and
      periodontal disease (group 4). Peripheral blood samples were collected at the beginning and
      at the end of the treatment of periodontal disease.
Inclusion criteria for PD were: presence of at least 15 teeth and clinical diagnosis of PD.
      Excluding third molars. This diagnosis was confirmed by the presence of at least 6 teeth with
      at least one noncontiguous interproximal site with Probing Pocket Depth (PPD) and Clinical
      Attachment Loss (CAL) ≥ 5 mm, as well as 30% of Sites with PPD and CAL ≥ 4mm and bleeding on
      Probing (BOP). Periodontal disease currently classified as Stage III Degree B. Periodontal
      healthy was defined as individuals who presented a periodontium without loss of insertion,
      with PPD ≤3 mm, BOP in less than 10% of the sites and without radiographic bone loss.

      Non-surgical periodontal treatment was performed, including oral hygiene education, scaling,
      smoothing and coronal-radicular polishing (RAR). Six sites were evaluated in each tooth
      (mesiobuccal, buccal, distobuccal, distolingual/palatal, lingual/palatal and
      mesiolingual/palatal surfaces). Scaling and root planing were performed using mechanical
      devices - ultrasound and manual instruments. The treatment was with local anesthesia, 3%
      lidocaine with vasoconstrictor, for PPD ≥ 5 mm. The objective of each session was to achieve
      a smooth surface, devoid of biofilm and calculus.

      The following parameters are evaluated during clinical examination: Probing Pocket Depth
      (PPD), distance of the enamel-cementum line at the gingival margin, clinical Attachment Loss
      (CAL), plaque index (IP) and bleeding on probing (BOP), PPD and CAL measurements are rounded
      to the nearest millimeter using a North Carolina periodontal probe (Chicago, USA).
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: After improving the periodontal clinical aspects, we observed whether there was an impact on serum levels of mannose-binding lectin (MBL) protein.
time frame: The periodontal treatment was performed and at the end of three-month period blood sample was collected.
description: Non-surgical periodontal treatment was performed to treat the periodontal disease and it included oral hygiene education, scaling, smoothing and polishing of the root and dental crown (RAR). Blood sample was collected at baseline and at the end of study.
measure: After improving the periodontal clinical aspects, we observed whether there was an impact on serum levels of sirtuin-1 (SIRT1) protein.
time frame: The periodontal treatment was performed and at the end of three-month period blood sample was collected.
description: Non-surgical periodontal treatment was performed to treat the periodontal disease and it included oral hygiene education, scaling, smoothing and polishing of the root and dental crown (RAR). Blood sample was collected at baseline and at the end of study.
arm group label: Group 1
arm group type: No Intervention
description: 20 patients without periodontal disease and coronary artery disease
arm group label: Group 2
arm group type: No Intervention
description: 20 patients without periodontal disease and with coronary artery disease
arm group label: Group 3
arm group type: Active Comparator
description: 20 patients with periodontal disease and with coronary artery disease received treatment of periodontal disease
arm group label: Group 4
arm group type: Active Comparator
description: 20 patients with periodontal disease and without coronary artery disease received treatment of periodontal disease
intervention type: Procedure
intervention name: treatment of periodontal disease
description: Patients with periodontal disease received treatment of periodontal disease through ultrasound or manual scaling of dental calculations. In addition to receiving instructions to improve oral health, such as the correct use of dental floss, adequate time and the correct way to brush.
arm group label: Group 3
arm group label: Group 4
criteria: 
gender: All
minimum age: 45 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Antonio P Mansur, 1
role: Principal Investigator
affiliation: Universidade de São Paulo, São Paulo, SP, BR
facility: 
facility: 
country: Brazil
citation: Mansur AP, Roggerio A, Goes MFS, Avakian SD, Leal DP, Maranhao RC, Strunz CMC. Serum concentrations and gene expression of sirtuin 1 in healthy and slightly overweight subjects after caloric restriction or resveratrol supplementation: A randomized trial. Int J Cardiol. 2017 Jan 15;227:788-794. doi: 10.1016/j.ijcard.2016.10.058. Epub 2016 Oct 27.
PMID: 28029409
citation: Liukkonen A, He Q, Gursoy UK, Pussinen PJ, Grondahl-Yli-Hannuksela K, Liukkonen J, Sorsa T, Suominen AL, Huumonen S, Kononen E. Mannose-binding lectin gene polymorphism in relation to periodontal infection. J Periodontal Res. 2017 Jun;52(3):540-545. doi: 10.1111/jre.12420. Epub 2016 Sep 14.
PMID: 27624657
citation: Tsutsumi A, Kobayashi T, Ito S, Goto D, Matsumoto I, Yoshie H, Sumida T. Mannose binding lectin gene polymorphism and the severity of chronic periodontitis. Nihon Rinsho Meneki Gakkai Kaishi. 2009 Feb;32(1):48-52. doi: 10.2177/jsci.32.48.
PMID: 19252378
citation: Louropoulou A, van der Velden U, Schoenmaker T, Catsburg A, Savelkoul PH, Loos BG. Mannose-binding lectin gene polymorphisms in relation to periodontitis. J Clin Periodontol. 2008 Nov;35(11):923-30. doi: 10.1111/j.1600-051X.2008.01311.x. Epub 2008 Sep 20.
PMID: 18823346
citation: Mattagajasingh I, Kim CS, Naqvi A, Yamamori T, Hoffman TA, Jung SB, DeRicco J, Kasuno K, Irani K. SIRT1 promotes endothelium-dependent vascular relaxation by activating endothelial nitric oxide synthase. Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14855-60. doi: 10.1073/pnas.0704329104. Epub 2007 Sep 4.
PMID: 17785417
responsible party type: Principal Investigator
investigator affiliation: InCor Heart Institute
investigator full name: ANTONIO DE PADUA MANSUR
investigator title: Principal Investigator
mesh term: Periodontal Diseases
sharing ipd: No
provided document: 
provided document: 
submitted: December 4, 2018
returned: March 15, 2019
submitted: July 12, 2020
returned: July 29, 2020