xml: <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/NCT05975892</url>
    </required_header>
    <id_info>
      <org_study_id>IVIC-UTC-MSC-Periodontal</org_study_id>
      <nct_id>NCT05975892</nct_id>
    </id_info>
    <brief_title>Transplantation of Bone Marrow Mesenchymal Stromal Cells for Periodontal Regeneration</brief_title>
    <acronym>BMMSC</acronym>
    <official_title>Transplantation of Bone Marrow Mesenchymal Stromal Cells for Bone Regeneration in Periodontal Disease</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Instituto Venezolano de Investigaciones Cientificas</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Universidad Central de Venezuela</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Hospital Central Dr. Plácido D. Rodriguez Rivero, San Felipe, Yaracuy</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Instituto Venezolano de Investigaciones Cientificas</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 goal of this study is to evaluate the capacity of allogeneic bone marrow mesenchymal&#xD;
        stromal cells (MSC) to induce bone regeneration in patients with periodontal disease. MSC&#xD;
        cultured are loaded on a collagen scaffold, included into autologous platelet rich plasma&#xD;
        clot and implanted in the bone defect.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The clinical protocol is designed to evaluate the bone regeneration capacity of allogeneic&#xD;
        MSCs for the treatment of patients with chronic or aggressive periodontal disease. Patients&#xD;
        with either a 2- or 3-wall intrabony defects are included in this study. A bioengineering&#xD;
        construct, constituted by allogeneic MSCs and a collagen scaffold, is incorporated into&#xD;
        platelet rich plasma (PRP) clot, which is implanted at the bone defect site. Follow up of&#xD;
        treated tooth are assessed by clinical evaluation, intraoral radiography and cone-beam CT.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Enrolling by invitation</overall_status>
    <start_date type="Actual">August 30, 2018</start_date>
    <completion_date type="Anticipated">August 30, 2024</completion_date>
    <primary_completion_date type="Actual">August 30, 2022</primary_completion_date>
    <phase>Phase 1/Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Change in clinical attachment level (CAL)</measure>
      <time_frame>Follow-up includes evaluation at 3, 6, 9 and 12 months post-transplantation</time_frame>
      <description>Expressed as the distance in millimeters from the cemento-enamel junction (CEJ) to the bottom of the probable gingival/periodontal pocket.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in probing pocket depth (PPD)</measure>
      <time_frame>Follow-up includes evaluation at 3, 6, 9 and 12 months post-transplantation</time_frame>
      <description>The distance from the gingival margin to the bottom of the gingival sulcus/pocket, is measured by means of periodontal probe.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Gingival recession (GR)</measure>
      <time_frame>Follow-up includes evaluation at 3, 6, 9 and 12 months post-transplantation</time_frame>
      <description>Exposure of the tooth through apical migration of the gingiva will be recorded as the distance in millimeters from the CEJ to the gingival margin</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in bone density</measure>
      <time_frame>Follow-up includes evaluation at 3, 6, 9 and 12 months post-transplantation</time_frame>
      <description>Changes in the density of the periodontal bone defect will be detected by Cone beam Tomography</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in Tooth Mobility (TM)</measure>
      <time_frame>Follow-up includes evaluation at 3, 6, 9 and 12 months post-transplantation</time_frame>
      <description>Changes from baseline in tooth mobility will be recorded.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in bone depth</measure>
      <time_frame>Follow-up includes evaluation at 3, 6, 9 and 12 months post-transplantation</time_frame>
      <description>The vertical bone defects will be assessed by X-rays. The postoperative depth of the intrabony defect will be calculated from the distance between the cemento-enamel junction and the bone crest on the preoperative and postoperative radiographs at the same magnification.</description>
    </primary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">30</enrollment>
    <condition>Chronic Periodontal Disease</condition>
    <condition>Aggressive Periodontitis</condition>
    <arm_group>
      <arm_group_label>Allogeneic MSCs transplantation in periodontal disease</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Allogeneic MSC harvested and cultured in osteogenic medium are seeded on collagen scaffold, mixed with autologous platelet rich plasma clot. The MSCs construct (MSCs/Coll/PRP clot) is implanted in the bone defect.</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Transplantation of allogeneic MSCs in periodontal disease</intervention_name>
      <description>Oral surgery is performed in patients with periodontal disease, under local anesthesia. An incision will be made on the periodontal lesion, A full-thickness flap is elevated on both the buccal and lingual areas and the inner epithelium of the flap removed. Granulation tissue is removed from bone defect area, and a root planning is performed. MSC construct is placed around the bone defect and a collagen membrane is used to cover and close off the bone defect site. The flap will be repositioned and the wound closed by a suture</description>
      <arm_group_label>Allogeneic MSCs transplantation in periodontal disease</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Medical healthy&#xD;
  &#xD;
            -  Minimum age of 18 years old&#xD;
  &#xD;
            -  Diagnosis of chronic or aggressive periodontitis&#xD;
  &#xD;
            -  Vertical intrabony defects of three or two walls&#xD;
  &#xD;
            -  PPD &gt;= 5 mm&#xD;
  &#xD;
            -  Radiographic evidence of alveolar bone loss of at least 3 mm&#xD;
  &#xD;
            -  Minimim 20 teeth presents in mouth.&#xD;
  &#xD;
            -  Informed consent of the patient&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Smoking&#xD;
  &#xD;
            -  Pregnancy or lactating&#xD;
  &#xD;
            -  Receiving immunosuppressive drugs, anticoagulants, antibiotics or analgesic drugs&#xD;
  &#xD;
            -  Diabetics&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Jose E Cardier Montalvo, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Instituto Venezolano de Investigaciones Cientificas</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>Instituto Venezolano de Investigaciones Cientificas</name>
        <address>
          <city>Caracas</city>
          <state>Miranda</state>
          <zip>1204</zip>
          <country>Venezuela</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Venezuela</country>
    </location_countries>
    <reference>
      <citation>Wittig O, Diaz-Solano D, Cardier J. Viability and functionality of mesenchymal stromal cells loaded on collagen microspheres and incorporated into plasma clots for orthopaedic application: Effect of storage conditions. Injury. 2018 Jun;49(6):1052-1057. doi: 10.1016/j.injury.2018.04.005. Epub 2018 Apr 5.</citation>
      <PMID>29678307</PMID>
    </reference>
    <reference>
      <citation>Wittig O, Romano E, Gonzalez C, Diaz-Solano D, Marquez ME, Tovar P, Aoun R, Cardier JE. A method of treatment for nonunion after fractures using mesenchymal stromal cells loaded on collagen microspheres and incorporated into platelet-rich plasma clots. Int Orthop. 2016 May;40(5):1033-8. doi: 10.1007/s00264-016-3130-6. Epub 2016 Mar 16.</citation>
      <PMID>26980620</PMID>
    </reference>
    <reference>
      <citation>Gomez M, Wittig O, Diaz-Solano D, Cardier JE. Mesenchymal Stromal Cell Transplantation Induces Regeneration of Large and Full-Thickness Cartilage Defect of the Temporomandibular Joint. Cartilage. 2021 Dec;13(1_suppl):1814S-1821S. doi: 10.1177/1947603520926711. Epub 2020 Jun 4.</citation>
      <PMID>32493042</PMID>
    </reference>
    <reference>
      <citation>Gomez-Sosa JF, Diaz-Solano D, Wittig O, Cardier JE. Dental Pulp Regeneration Induced by Allogenic Mesenchymal Stromal Cell Transplantation in a Mature Tooth: A Case Report. J Endod. 2022 Jun;48(6):736-740. doi: 10.1016/j.joen.2022.03.002. Epub 2022 Mar 18.</citation>
      <PMID>35307516</PMID>
    </reference>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 14, 2023</study_first_submitted>
    <study_first_submitted_qc>July 27, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 4, 2023</study_first_posted>
    <last_update_submitted>July 27, 2023</last_update_submitted>
    <last_update_submitted_qc>July 27, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 4, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Instituto Venezolano de Investigaciones Cientificas</investigator_affiliation>
      <investigator_full_name>Dylana Diaz Solano</investigator_full_name>
      <investigator_title>Clinical Investigator</investigator_title>
    </responsible_party>
    <keyword>Mesenchymal stromal cells</keyword>
    <keyword>Periodontal regeneration</keyword>
    <keyword>Bone regeneration</keyword>
    <keyword>Periodontitis</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Periodontitis</mesh_term>
      <mesh_term>Periodontal Diseases</mesh_term>
      <mesh_term>Aggressive Periodontitis</mesh_term>
      <mesh_term>Chronic Periodontitis</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05975892
  org study id: IVIC-UTC-MSC-Periodontal
  nct id: NCT05975892
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this study is to evaluate the capacity of allogeneic bone marrow mesenchymal
        stromal cells (MSC) to induce bone regeneration in patients with periodontal disease. MSC
        cultured are loaded on a collagen scaffold, included into autologous platelet rich plasma
        clot and implanted in the bone defect.
  The clinical protocol is designed to evaluate the bone regeneration capacity of allogeneic
        MSCs for the treatment of patients with chronic or aggressive periodontal disease. Patients
        with either a 2- or 3-wall intrabony defects are included in this study. A bioengineering
        construct, constituted by allogeneic MSCs and a collagen scaffold, is incorporated into
        platelet rich plasma (PRP) clot, which is implanted at the bone defect site. Follow up of
        treated tooth are assessed by clinical evaluation, intraoral radiography and cone-beam CT.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Change in clinical attachment level (CAL)
  time frame: Follow-up includes evaluation at 3, 6, 9 and 12 months post-transplantation
  description: Expressed as the distance in millimeters from the cemento-enamel junction (CEJ) to the bottom of the probable gingival/periodontal pocket.
  measure: Change in probing pocket depth (PPD)
  time frame: Follow-up includes evaluation at 3, 6, 9 and 12 months post-transplantation
  description: The distance from the gingival margin to the bottom of the gingival sulcus/pocket, is measured by means of periodontal probe.
  measure: Gingival recession (GR)
  time frame: Follow-up includes evaluation at 3, 6, 9 and 12 months post-transplantation
  description: Exposure of the tooth through apical migration of the gingiva will be recorded as the distance in millimeters from the CEJ to the gingival margin
  measure: Change in bone density
  time frame: Follow-up includes evaluation at 3, 6, 9 and 12 months post-transplantation
  description: Changes in the density of the periodontal bone defect will be detected by Cone beam Tomography
  measure: Change in Tooth Mobility (TM)
  time frame: Follow-up includes evaluation at 3, 6, 9 and 12 months post-transplantation
  description: Changes from baseline in tooth mobility will be recorded.
  measure: Change in bone depth
  time frame: Follow-up includes evaluation at 3, 6, 9 and 12 months post-transplantation
  description: The vertical bone defects will be assessed by X-rays. The postoperative depth of the intrabony defect will be calculated from the distance between the cemento-enamel junction and the bone crest on the preoperative and postoperative radiographs at the same magnification.
  arm group label: Allogeneic MSCs transplantation in periodontal disease
  arm group type: Experimental
  description: Allogeneic MSC harvested and cultured in osteogenic medium are seeded on collagen scaffold, mixed with autologous platelet rich plasma clot. The MSCs construct (MSCs/Coll/PRP clot) is implanted in the bone defect.
  intervention type: Biological
  intervention name: Transplantation of allogeneic MSCs in periodontal disease
  description: Oral surgery is performed in patients with periodontal disease, under local anesthesia. An incision will be made on the periodontal lesion, A full-thickness flap is elevated on both the buccal and lingual areas and the inner epithelium of the flap removed. Granulation tissue is removed from bone defect area, and a root planning is performed. MSC construct is placed around the bone defect and a collagen membrane is used to cover and close off the bone defect site. The flap will be repositioned and the wound closed by a suture
  arm group label: Allogeneic MSCs transplantation in periodontal disease
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Jose E Cardier Montalvo, MD, PhD
  role: Principal Investigator
  affiliation: Instituto Venezolano de Investigaciones Cientificas
  facility: 
  country: Venezuela
  citation: Wittig O, Diaz-Solano D, Cardier J. Viability and functionality of mesenchymal stromal cells loaded on collagen microspheres and incorporated into plasma clots for orthopaedic application: Effect of storage conditions. Injury. 2018 Jun;49(6):1052-1057. doi: 10.1016/j.injury.2018.04.005. Epub 2018 Apr 5.
  PMID: 29678307
  citation: Wittig O, Romano E, Gonzalez C, Diaz-Solano D, Marquez ME, Tovar P, Aoun R, Cardier JE. A method of treatment for nonunion after fractures using mesenchymal stromal cells loaded on collagen microspheres and incorporated into platelet-rich plasma clots. Int Orthop. 2016 May;40(5):1033-8. doi: 10.1007/s00264-016-3130-6. Epub 2016 Mar 16.
  PMID: 26980620
  citation: Gomez M, Wittig O, Diaz-Solano D, Cardier JE. Mesenchymal Stromal Cell Transplantation Induces Regeneration of Large and Full-Thickness Cartilage Defect of the Temporomandibular Joint. Cartilage. 2021 Dec;13(1_suppl):1814S-1821S. doi: 10.1177/1947603520926711. Epub 2020 Jun 4.
  PMID: 32493042
  citation: Gomez-Sosa JF, Diaz-Solano D, Wittig O, Cardier JE. Dental Pulp Regeneration Induced by Allogenic Mesenchymal Stromal Cell Transplantation in a Mature Tooth: A Case Report. J Endod. 2022 Jun;48(6):736-740. doi: 10.1016/j.joen.2022.03.002. Epub 2022 Mar 18.
  PMID: 35307516
  responsible party type: Principal Investigator
  investigator affiliation: Instituto Venezolano de Investigaciones Cientificas
  investigator full name: Dylana Diaz Solano
  investigator title: Clinical Investigator
  mesh term: Periodontitis
  mesh term: Periodontal Diseases
  mesh term: Aggressive Periodontitis
  mesh term: Chronic Periodontitis
  sharing ipd: No