<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/NCT03806361</url>
  </required_header>
  <id_info>
    <org_study_id>Hospital Sirio Libanes</org_study_id>
    <nct_id>NCT03806361</nct_id>
  </id_info>
  <brief_title>Fat Grafts With Adipose-derived Regenerative Cells for Soft Tissue Reconstruction in Children</brief_title>
  <official_title>Fat Grafts Supplemented With Adipose-derived Regenerative Cells for Soft Tissue Reconstruction in Children With Craniofacial Microsomia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital Sirio-Libanes</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital Sirio-Libanes</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>
      Although first reports of the clinical use of adipose-derived regenerative cells (ADRC)&#xD;
      suggest that this approach may be feasible and effective for soft tissue augmentation, there&#xD;
      is a lack of randomized, controlled clinical trials in the literature. Hence, this study&#xD;
      aimed to investigate whether a novel protocol for isolation of ADRC and their use in&#xD;
      combination with fat tissue improve the long-term retention of the grafts in paediatric&#xD;
      patients with craniofacial microsomia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      To overcome problems associated with fat grafting, such as unpredictable clinical results and&#xD;
      a low rate of graft survival, many innovative efforts and refinements of surgical techniques&#xD;
      have been reported. For example, condensation of living tissue and removal of unnecessary&#xD;
      components have been performed by centrifugation, filtration or gravity sedimentation;&#xD;
      external mechanical force has been used to expand the recipient tissue as well as the&#xD;
      overlying skin envelope; and a recent experimental study has suggested that repeated local&#xD;
      injections of erythropoietin might enhance retention of grafted fat.&#xD;
&#xD;
      Based on the finding that aspirated fat tissue contains a much smaller number of&#xD;
      adipose-derived regenerative cells (ADRC) compared with intact tissue and that these cells&#xD;
      play pivotal roles in the adipose tissue remodeling after lipoinjection, the supplementation&#xD;
      of fat grafts with stromal vascular fraction isolated from adipose portion of liposuction&#xD;
      aspirates has been proposed as a method to compensate its relative deficiency of ADRC.&#xD;
&#xD;
      In the literature, there are at least three experimental studies demonstrating that&#xD;
      supplementation of adipose progenitor cells enhances the volume or weight of surviving&#xD;
      adipose tissue, and first reports of the clinical use of ADRC suggest that this approach may&#xD;
      be feasible and effective for soft tissue augmentation.&#xD;
&#xD;
      However, since these studies represent level of evidence IV, which correspond to the&#xD;
      publication of case series, there is a lack of randomized, controlled clinical trials&#xD;
      comparing this method to current standard techniques.&#xD;
&#xD;
      Hence, this study aimed to fill this gap by investigating whether a novel protocol for&#xD;
      isolation of ADRC and their use in combination with fat tissue improve the long-term&#xD;
      retention of the grafts in paediatric patients with craniofacial microsomia.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 10, 2019</start_date>
  <completion_date type="Actual">January 10, 2021</completion_date>
  <primary_completion_date type="Actual">January 10, 2021</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>Randomized, controlled, clinical trial with 2 parallel comparison groups</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
    <masking_description>Subjects will not know which treatment they will receive, outcome assessors will also be blinded.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Volumetric analysis of both hemifaces</measure>
    <time_frame>Preoperative, 1 month postoperative, 3 months postoperative and 6 months postoperative</time_frame>
    <description>Preoperative and 1, 3 and 6-months postoperative 3D-photogrammetry will be performed for volumetric measurements of both hemifaces using Vectra H1 software. Volumetric augmentation will be noticed for each patient by comparing the change between volumes of affected and unaffected hemifaces in the preoperative and 1, 3 and 6 months postoperative periods, which will be considered the retention volume. The percentage of fat graft survival will be determined as a ratio of the retention volume to the preoperative difference between volumes of affected and unaffected hemifaces.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of viable cells</measure>
    <time_frame>Intraoperative and immediate postoperative period</time_frame>
    <description>Immediately after the surgical procedure the number of viable cells isolated before and after the supplementation of the grafts will be counted using the trypan blue dye exclusion assay in a Neubauer chamber using the light microscope Nikon Eclipse TS100 (Nikon Instruments Inc., NY, USA). Next, immunophenotype characterization of cell populations on passage 1 will be done by flow cytometric analysis with the anti-human antibodies CD29, CD31, CD45, CD90, CD73 and CD105 (Becton, Dickinson and Company, NJ, USA) in a Guava EasyCyte flow cytometer running the Guava Express Plus software (Guava Technologies Hayward, CA, USA).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Craniofacial Microsomia</condition>
  <arm_group>
    <arm_group_label>With ADRC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Supplementation of fat grafts with ADRC</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Structural</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Structural fat grafting</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Fat grafts supplemented with ADRC</intervention_name>
    <description>Isolation of ADRC from fat aspirates and its use for supplementation of fat grafts.</description>
    <arm_group_label>With ADRC</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Structural fat grafting</intervention_name>
    <description>Fat grafts without supplementation of ADRC</description>
    <arm_group_label>Structural</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Unilateral craniofacial microsomia&#xD;
&#xD;
          -  10 to 18 years old&#xD;
&#xD;
          -  Phenotype: (M0, M1 or M2) and (S1 or S2) according to the OMENS-Plus classification&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous facial soft tissue surgery&#xD;
&#xD;
          -  Absence of fat donor site&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>10 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Hospital Municipal Infantil Menino Jesus</name>
      <address>
        <city>São Paulo</city>
        <state>SP</state>
        <zip>01329-010</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>January 9, 2019</study_first_submitted>
  <study_first_submitted_qc>January 14, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 16, 2019</study_first_posted>
  <last_update_submitted>October 15, 2021</last_update_submitted>
  <last_update_submitted_qc>October 15, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 18, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hospital Sirio-Libanes</investigator_affiliation>
    <investigator_full_name>Daniela S Tanikawa</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>Goldenhar Syndrome</mesh_term>
    <mesh_term>Fetal Growth Retardation</mesh_term>
  </condition_browse>
  <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/NCT03806361
org study id: Hospital Sirio Libanes
nct id: NCT03806361
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Although first reports of the clinical use of adipose-derived regenerative cells (ADRC)
      suggest that this approach may be feasible and effective for soft tissue augmentation, there
      is a lack of randomized, controlled clinical trials in the literature. Hence, this study
      aimed to investigate whether a novel protocol for isolation of ADRC and their use in
      combination with fat tissue improve the long-term retention of the grafts in paediatric
      patients with craniofacial microsomia.
To overcome problems associated with fat grafting, such as unpredictable clinical results and
      a low rate of graft survival, many innovative efforts and refinements of surgical techniques
      have been reported. For example, condensation of living tissue and removal of unnecessary
      components have been performed by centrifugation, filtration or gravity sedimentation;
      external mechanical force has been used to expand the recipient tissue as well as the
      overlying skin envelope; and a recent experimental study has suggested that repeated local
      injections of erythropoietin might enhance retention of grafted fat.

      Based on the finding that aspirated fat tissue contains a much smaller number of
      adipose-derived regenerative cells (ADRC) compared with intact tissue and that these cells
      play pivotal roles in the adipose tissue remodeling after lipoinjection, the supplementation
      of fat grafts with stromal vascular fraction isolated from adipose portion of liposuction
      aspirates has been proposed as a method to compensate its relative deficiency of ADRC.

      In the literature, there are at least three experimental studies demonstrating that
      supplementation of adipose progenitor cells enhances the volume or weight of surviving
      adipose tissue, and first reports of the clinical use of ADRC suggest that this approach may
      be feasible and effective for soft tissue augmentation.

      However, since these studies represent level of evidence IV, which correspond to the
      publication of case series, there is a lack of randomized, controlled clinical trials
      comparing this method to current standard techniques.

      Hence, this study aimed to fill this gap by investigating whether a novel protocol for
      isolation of ADRC and their use in combination with fat tissue improve the long-term
      retention of the grafts in paediatric patients with craniofacial microsomia.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized, controlled, clinical trial with 2 parallel comparison groups
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
masking description: Subjects will not know which treatment they will receive, outcome assessors will also be blinded.
measure: Volumetric analysis of both hemifaces
time frame: Preoperative, 1 month postoperative, 3 months postoperative and 6 months postoperative
description: Preoperative and 1, 3 and 6-months postoperative 3D-photogrammetry will be performed for volumetric measurements of both hemifaces using Vectra H1 software. Volumetric augmentation will be noticed for each patient by comparing the change between volumes of affected and unaffected hemifaces in the preoperative and 1, 3 and 6 months postoperative periods, which will be considered the retention volume. The percentage of fat graft survival will be determined as a ratio of the retention volume to the preoperative difference between volumes of affected and unaffected hemifaces.
measure: Number of viable cells
time frame: Intraoperative and immediate postoperative period
description: Immediately after the surgical procedure the number of viable cells isolated before and after the supplementation of the grafts will be counted using the trypan blue dye exclusion assay in a Neubauer chamber using the light microscope Nikon Eclipse TS100 (Nikon Instruments Inc., NY, USA). Next, immunophenotype characterization of cell populations on passage 1 will be done by flow cytometric analysis with the anti-human antibodies CD29, CD31, CD45, CD90, CD73 and CD105 (Becton, Dickinson and Company, NJ, USA) in a Guava EasyCyte flow cytometer running the Guava Express Plus software (Guava Technologies Hayward, CA, USA).
arm group label: With ADRC
arm group type: Experimental
description: Supplementation of fat grafts with ADRC
arm group label: Structural
arm group type: Active Comparator
description: Structural fat grafting
intervention type: Procedure
intervention name: Fat grafts supplemented with ADRC
description: Isolation of ADRC from fat aspirates and its use for supplementation of fat grafts.
arm group label: With ADRC
intervention type: Procedure
intervention name: Structural fat grafting
description: Fat grafts without supplementation of ADRC
arm group label: Structural
criteria: 
gender: All
minimum age: 10 Years
maximum age: 18 Years
healthy volunteers: No
facility: 
country: Brazil
responsible party type: Principal Investigator
investigator affiliation: Hospital Sirio-Libanes
investigator full name: Daniela S Tanikawa
investigator title: Principal investigator
mesh term: Goldenhar Syndrome
mesh term: Fetal Growth Retardation
sharing ipd: No