<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/NCT03766217</url>
  </required_header>
  <id_info>
    <org_study_id>CAAE47719215.5.0000.5461</org_study_id>
    <nct_id>NCT03766217</nct_id>
  </id_info>
  <brief_title>Bone Tissue Engineering With Dental Pulp Stem Cells for Alveolar Cleft Repair</brief_title>
  <acronym>CLOSE</acronym>
  <official_title>Bone Tissue Engineering With Dental Pulp Stem Cells for Alveolar Cleft Repair</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital Sirio-Libanes</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ministry of Health, Brazil</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Hospital Sirio-Libanes</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Iliac crest autogenous bone graft is accepted as the most effective method for secondary&#xD;
      alveolar cleft repair. However this method is associated with complications. As an&#xD;
      alternative, mesenchymal stem cells associated with biomaterials have been used for the&#xD;
      rehabilitation of the alveolar bone cleft of patients with cleft lip and palate. This is a&#xD;
      RCT comparing mesenchymal stem cells obtained from autogenous deciduous dental pulp&#xD;
      associated with biomaterials versus iliac crest autogenous bone graft for secondary alveolar&#xD;
      cleft repair.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 5, 2019</start_date>
  <completion_date type="Actual">December 15, 2019</completion_date>
  <primary_completion_date type="Actual">December 6, 2019</primary_completion_date>
  <phase>Phase 3</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>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Alveolar bone filling rate</measure>
    <time_frame>12 months</time_frame>
    <description>Alveolar bone filling rate defined by the filling of at least 70% of the alveolar cleft area.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Serious adverse events</measure>
    <time_frame>12 months</time_frame>
    <description>Serious adverse events resulting in death, life-threatening event, hospitalization, prolongation of existing hospitalization (for &gt; 24 hours), persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions. Important medical event that may not result in death, be life threatening, or require hospitalization may be considered a serious adverse drug experience when, based upon medical judgment, it may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.&#xD;
Frequency of participants experiencing at least one serious adverse event.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Non serious adverse events</measure>
    <time_frame>15 days; 3, 6 and 12 months</time_frame>
    <description>Frequency of participants experiencing at least one non serious adverse event</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bone Tissue Engineering With Dental Pulp Stem Cells for Alveolar Cleft Repair</measure>
    <time_frame>Bone tissue engineering</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Position of the canine tooth and formation of dental root</measure>
    <time_frame>12 months</time_frame>
    <description>Position of the canine tooth and formation of dental root assessed by CT scan</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alveolar bone filling rate</measure>
    <time_frame>6 months</time_frame>
    <description>Alveolar bone filling rate defined by the filling of at least 70% of the alveolar cleft area.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serious adverse events</measure>
    <time_frame>15 days; 3 and 6 months</time_frame>
    <description>Serious adverse events resulting in death, life-threatening event, hospitalization, prolongation of existing hospitalization (for &gt; 24 hours), persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions. Important medical event that may not result in death, be life threatening, or require hospitalization may be considered a serious adverse drug experience when, based upon medical judgment, it may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.&#xD;
Frequency of participants experiencing at least one serious adverse event.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient-reported outcome (PRO, including appearance, fuction and quality of life)</measure>
    <time_frame>pre surgery and 12 months</time_frame>
    <description>Assessed by CLEFT-Q, a self-report PRO instrument, tool answered independently patients themselves, without interpretation by the parent(s) or healthcare provider. The CLEFT-Q consists of 13 independently functioning domains (171 items) measuring appearance, facial function and quality of life. Each domain is composed of a series of items that together evaluate a unidimensional construct. A higher score means a better result (continuous outcome, measured by: mean)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">62</enrollment>
  <condition>Cleft Lip and Palate</condition>
  <arm_group>
    <arm_group_label>Mesenchymal stem cells associated with biomaterials</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Mesenchymal stem cells obtained from autogenous deciduous dental pulp associated with biomaterials. The stem cells will be obtained by enzimatic digestion in GMP laboratory and will be seed into the biomaterial (hydroxyapatite/collagen).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Iliac crest autogenous bone graft</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Autogenous bone will be obtained from iliac crest. The prepare of the receptor area will be the same in both arms and will follow current recommendations.</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Mesenchymal stem cells associated with biomaterials</intervention_name>
    <description>Deciduous dental pulp mesenchymal stem cells associated with hydroxyapatita/collagen.</description>
    <arm_group_label>Mesenchymal stem cells associated with biomaterials</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Iliac crest autogenous bone graft</intervention_name>
    <description>Autogenous bone will be obtained from iliac crest.</description>
    <arm_group_label>Iliac crest autogenous bone graft</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  non syndromic unilateral cleft lip and palate;&#xD;
&#xD;
          -  age between 7 and 12 years;&#xD;
&#xD;
          -  to have the jaw aligned and ready to receive the graft.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  previous surgery to correct the alveolar cleft;&#xD;
&#xD;
          -  have the canine erupted before grafting;&#xD;
&#xD;
          -  incomplete orthodontic treatment;&#xD;
&#xD;
          -  incomplete CT scan documentation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>7 Years</minimum_age>
    <maximum_age>12 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Hospital Sírio-Libanes</name>
      <address>
        <city>São Paulo</city>
        <zip>01308-050</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <link>
    <url>https://www.hindawi.com/journals/sci/2020/6234167</url>
    <description>First results published</description>
  </link>
  <link>
    <url>https://www.hindawi.com/journals/sci/2019/7951696/</url>
    <description>&quot;in vitro&quot; results</description>
  </link>
  <reference>
    <citation>Tanikawa DYS, Pinheiro CCG, Almeida MCA, Oliveira CRGCM, Coudry RA, Rocha DL, Bueno DF. Deciduous Dental Pulp Stem Cells for Maxillary Alveolar Reconstruction in Cleft Lip and Palate Patients. Stem Cells Int. 2020 Mar 12;2020:6234167. doi: 10.1155/2020/6234167. eCollection 2020.</citation>
    <PMID>32256610</PMID>
  </reference>
  <reference>
    <citation>Pinheiro CCG, Leyendecker Junior A, Tanikawa DYS, Ferreira JRM, Jarrahy R, Bueno DF. Is There a Noninvasive Source of MSCs Isolated with GMP Methods with Better Osteogenic Potential? Stem Cells Int. 2019 Nov 6;2019:7951696. doi: 10.1155/2019/7951696. eCollection 2019.</citation>
    <PMID>31781247</PMID>
  </reference>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>November 29, 2018</study_first_submitted>
  <study_first_submitted_qc>December 4, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 6, 2018</study_first_posted>
  <last_update_submitted>May 11, 2020</last_update_submitted>
  <last_update_submitted_qc>May 11, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 13, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hospital Sirio-Libanes</investigator_affiliation>
    <investigator_full_name>Daniela Franco Bueno</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cleft Lip</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/NCT03766217
org study id: CAAE47719215.5.0000.5461
nct id: NCT03766217
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
is us export: No
Iliac crest autogenous bone graft is accepted as the most effective method for secondary
      alveolar cleft repair. However this method is associated with complications. As an
      alternative, mesenchymal stem cells associated with biomaterials have been used for the
      rehabilitation of the alveolar bone cleft of patients with cleft lip and palate. This is a
      RCT comparing mesenchymal stem cells obtained from autogenous deciduous dental pulp
      associated with biomaterials versus iliac crest autogenous bone graft for secondary alveolar
      cleft repair.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Alveolar bone filling rate
time frame: 12 months
description: Alveolar bone filling rate defined by the filling of at least 70% of the alveolar cleft area.
measure: Serious adverse events
time frame: 12 months
description: Serious adverse events resulting in death, life-threatening event, hospitalization, prolongation of existing hospitalization (for > 24 hours), persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions. Important medical event that may not result in death, be life threatening, or require hospitalization may be considered a serious adverse drug experience when, based upon medical judgment, it may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Frequency of participants experiencing at least one serious adverse event.
measure: Non serious adverse events
time frame: 15 days; 3, 6 and 12 months
description: Frequency of participants experiencing at least one non serious adverse event
measure: Bone Tissue Engineering With Dental Pulp Stem Cells for Alveolar Cleft Repair
time frame: Bone tissue engineering
measure: Position of the canine tooth and formation of dental root
time frame: 12 months
description: Position of the canine tooth and formation of dental root assessed by CT scan
measure: Alveolar bone filling rate
time frame: 6 months
description: Alveolar bone filling rate defined by the filling of at least 70% of the alveolar cleft area.
measure: Serious adverse events
time frame: 15 days; 3 and 6 months
description: Serious adverse events resulting in death, life-threatening event, hospitalization, prolongation of existing hospitalization (for > 24 hours), persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions. Important medical event that may not result in death, be life threatening, or require hospitalization may be considered a serious adverse drug experience when, based upon medical judgment, it may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Frequency of participants experiencing at least one serious adverse event.
measure: Patient-reported outcome (PRO, including appearance, fuction and quality of life)
time frame: pre surgery and 12 months
description: Assessed by CLEFT-Q, a self-report PRO instrument, tool answered independently patients themselves, without interpretation by the parent(s) or healthcare provider. The CLEFT-Q consists of 13 independently functioning domains (171 items) measuring appearance, facial function and quality of life. Each domain is composed of a series of items that together evaluate a unidimensional construct. A higher score means a better result (continuous outcome, measured by: mean)
arm group label: Mesenchymal stem cells associated with biomaterials
arm group type: Experimental
description: Mesenchymal stem cells obtained from autogenous deciduous dental pulp associated with biomaterials. The stem cells will be obtained by enzimatic digestion in GMP laboratory and will be seed into the biomaterial (hydroxyapatite/collagen).
arm group label: Iliac crest autogenous bone graft
arm group type: Active Comparator
description: Autogenous bone will be obtained from iliac crest. The prepare of the receptor area will be the same in both arms and will follow current recommendations.
intervention type: Combination Product
intervention name: Mesenchymal stem cells associated with biomaterials
description: Deciduous dental pulp mesenchymal stem cells associated with hydroxyapatita/collagen.
arm group label: Mesenchymal stem cells associated with biomaterials
intervention type: Combination Product
intervention name: Iliac crest autogenous bone graft
description: Autogenous bone will be obtained from iliac crest.
arm group label: Iliac crest autogenous bone graft
criteria: 
gender: All
minimum age: 7 Years
maximum age: 12 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Brazil
url: https://www.hindawi.com/journals/sci/2020/6234167
description: First results published
url: https://www.hindawi.com/journals/sci/2019/7951696/
description: "in vitro" results
citation: Tanikawa DYS, Pinheiro CCG, Almeida MCA, Oliveira CRGCM, Coudry RA, Rocha DL, Bueno DF. Deciduous Dental Pulp Stem Cells for Maxillary Alveolar Reconstruction in Cleft Lip and Palate Patients. Stem Cells Int. 2020 Mar 12;2020:6234167. doi: 10.1155/2020/6234167. eCollection 2020.
PMID: 32256610
citation: Pinheiro CCG, Leyendecker Junior A, Tanikawa DYS, Ferreira JRM, Jarrahy R, Bueno DF. Is There a Noninvasive Source of MSCs Isolated with GMP Methods with Better Osteogenic Potential? Stem Cells Int. 2019 Nov 6;2019:7951696. doi: 10.1155/2019/7951696. eCollection 2019.
PMID: 31781247
responsible party type: Principal Investigator
investigator affiliation: Hospital Sirio-Libanes
investigator full name: Daniela Franco Bueno
investigator title: Principal Investigator
mesh term: Cleft Lip