<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/NCT01674439</url>
  </required_header>
  <id_info>
    <org_study_id>1069/08</org_study_id>
    <secondary_id>CEPID-FAPESP 98/14254-2</secondary_id>
    <nct_id>NCT01674439</nct_id>
  </id_info>
  <brief_title>Clinical Trial of Fat Grafts Supplemented With Adipose-derived Regenerative Cells</brief_title>
  <official_title>Randomized Controlled Clinical Trial of Fat Grafts Supplemented With Adipose-derived Regenerative Cells for Facial Soft Tissue Augmentation in Patients With Craniofacial Microsomia.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Sao Paulo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Sao Paulo</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </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 patients with&#xD;
      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 patients with craniofacial microsomia.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2010</start_date>
  <completion_date type="Actual">July 2012</completion_date>
  <primary_completion_date type="Actual">July 2012</primary_completion_date>
  <phase>Phase 2</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>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Graft volume retention</measure>
    <time_frame>6 months postoperative</time_frame>
    <description>Graft volume retention evaluated by CT-scan performed at the preoperative period and at 6-months postoperative</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of viable cells before and after the supplementation of the grafts</measure>
    <time_frame>immediate postoperative</time_frame>
    <description>Number of viable cells in adipose tissue evaluated by trypan blue method immediately after surgery</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">29</enrollment>
  <condition>Craniofacial Microsomia</condition>
  <arm_group>
    <arm_group_label>With supplementation of ADRC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Fat graft with supplementation of ADRC</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Without supplementation of ADRC</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Fat grafts without supplementation of ADRC</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Supplementation of ADRC</intervention_name>
    <description>Isolation of ADRC from half of the aspirated fat and supplementation of the fat grafts with these cells</description>
    <arm_group_label>With supplementation of ADRC</arm_group_label>
    <other_name>Cell-assisted lipotransfer</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Without supplementation of ADRC</intervention_name>
    <description>Standard fat graft preparation</description>
    <arm_group_label>Without supplementation of ADRC</arm_group_label>
    <other_name>Structural fat grafting</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Unilateral craniofacial microsomia&#xD;
&#xD;
          -  10 to 35 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 soft tissue surgery&#xD;
&#xD;
          -  Absence of fat donor site&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>10 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Daniela Y Tanikawa, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Division of Plastic and Reconstructive Surgery, University of São Paulo School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Division of Plastic and Reconstructive Surgery</name>
      <address>
        <city>Sao Paulo</city>
        <state>SP</state>
        <zip>01246000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <results_reference>
    <citation>Yoshimura K, Sato K, Aoi N, Kurita M, Hirohi T, Harii K. Cell-assisted lipotransfer for cosmetic breast augmentation: supportive use of adipose-derived stem/stromal cells. Aesthetic Plast Surg. 2008 Jan;32(1):48-55; discussion 56-7. doi: 10.1007/s00266-007-9019-4. Epub 2007 Sep 1.</citation>
    <PMID>17763894</PMID>
  </results_reference>
  <results_reference>
    <citation>Yoshimura K, Sato K, Aoi N, Kurita M, Inoue K, Suga H, Eto H, Kato H, Hirohi T, Harii K. Cell-assisted lipotransfer for facial lipoatrophy: efficacy of clinical use of adipose-derived stem cells. Dermatol Surg. 2008 Sep;34(9):1178-85. doi: 10.1111/j.1524-4725.2008.34256.x. Epub 2008 May 29.</citation>
    <PMID>18513295</PMID>
  </results_reference>
  <results_reference>
    <citation>Yoshimura K, Asano Y, Aoi N, Kurita M, Oshima Y, Sato K, Inoue K, Suga H, Eto H, Kato H, Harii K. Progenitor-enriched adipose tissue transplantation as rescue for breast implant complications. Breast J. 2010 Mar-Apr;16(2):169-75. doi: 10.1111/j.1524-4741.2009.00873.x. Epub 2009 Nov 12.</citation>
    <PMID>19912236</PMID>
  </results_reference>
  <results_reference>
    <citation>Yoshimura K, Eto H, Kato H, Doi K, Aoi N. In vivo manipulation of stem cells for adipose tissue repair/reconstruction. Regen Med. 2011 Nov;6(6 Suppl):33-41. doi: 10.2217/rme.11.62.</citation>
    <PMID>21999260</PMID>
  </results_reference>
  <verification_date>August 2012</verification_date>
  <study_first_submitted>August 22, 2012</study_first_submitted>
  <study_first_submitted_qc>August 27, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 28, 2012</study_first_posted>
  <last_update_submitted>August 27, 2012</last_update_submitted>
  <last_update_submitted_qc>August 27, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 28, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Sao Paulo</investigator_affiliation>
    <investigator_full_name>Daniela Y. S. Tanikawa</investigator_full_name>
    <investigator_title>MD, Assistant Physician</investigator_title>
  </responsible_party>
  <keyword>Adipose-derived regenerative cells</keyword>
  <keyword>Cell therapy</keyword>
  <keyword>Autologous fat transfer</keyword>
  <keyword>Tissue engineering</keyword>
  <keyword>Craniofacial microsomia</keyword>
  <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>
  <!-- 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/NCT01674439
org study id: 1069/08
secondary id: CEPID-FAPESP 98/14254-2
nct id: NCT01674439
lead sponsor: 
has dmc: 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 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 patients with craniofacial microsomia.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Graft volume retention
time frame: 6 months postoperative
description: Graft volume retention evaluated by CT-scan performed at the preoperative period and at 6-months postoperative
measure: Number of viable cells before and after the supplementation of the grafts
time frame: immediate postoperative
description: Number of viable cells in adipose tissue evaluated by trypan blue method immediately after surgery
arm group label: With supplementation of ADRC
arm group type: Experimental
description: Fat graft with supplementation of ADRC
arm group label: Without supplementation of ADRC
arm group type: Active Comparator
description: Fat grafts without supplementation of ADRC
intervention type: Procedure
intervention name: Supplementation of ADRC
description: Isolation of ADRC from half of the aspirated fat and supplementation of the fat grafts with these cells
arm group label: With supplementation of ADRC
other name: Cell-assisted lipotransfer
intervention type: Procedure
intervention name: Without supplementation of ADRC
description: Standard fat graft preparation
arm group label: Without supplementation of ADRC
other name: Structural fat grafting
criteria: 
gender: All
minimum age: 10 Years
maximum age: 35 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Daniela Y Tanikawa, MD
role: Principal Investigator
affiliation: Division of Plastic and Reconstructive Surgery, University of São Paulo School of Medicine
facility: 
country: Brazil
citation: Yoshimura K, Sato K, Aoi N, Kurita M, Hirohi T, Harii K. Cell-assisted lipotransfer for cosmetic breast augmentation: supportive use of adipose-derived stem/stromal cells. Aesthetic Plast Surg. 2008 Jan;32(1):48-55; discussion 56-7. doi: 10.1007/s00266-007-9019-4. Epub 2007 Sep 1.
PMID: 17763894
citation: Yoshimura K, Sato K, Aoi N, Kurita M, Inoue K, Suga H, Eto H, Kato H, Hirohi T, Harii K. Cell-assisted lipotransfer for facial lipoatrophy: efficacy of clinical use of adipose-derived stem cells. Dermatol Surg. 2008 Sep;34(9):1178-85. doi: 10.1111/j.1524-4725.2008.34256.x. Epub 2008 May 29.
PMID: 18513295
citation: Yoshimura K, Asano Y, Aoi N, Kurita M, Oshima Y, Sato K, Inoue K, Suga H, Eto H, Kato H, Harii K. Progenitor-enriched adipose tissue transplantation as rescue for breast implant complications. Breast J. 2010 Mar-Apr;16(2):169-75. doi: 10.1111/j.1524-4741.2009.00873.x. Epub 2009 Nov 12.
PMID: 19912236
citation: Yoshimura K, Eto H, Kato H, Doi K, Aoi N. In vivo manipulation of stem cells for adipose tissue repair/reconstruction. Regen Med. 2011 Nov;6(6 Suppl):33-41. doi: 10.2217/rme.11.62.
PMID: 21999260
responsible party type: Principal Investigator
investigator affiliation: University of Sao Paulo
investigator full name: Daniela Y. S. Tanikawa
investigator title: MD, Assistant Physician
mesh term: Goldenhar Syndrome
mesh term: Fetal Growth Retardation