<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/NCT03792360</url>
  </required_header>
  <id_info>
    <org_study_id>17-003774</org_study_id>
    <nct_id>NCT03792360</nct_id>
  </id_info>
  <brief_title>Adipose Derived SVF for Aero-digestive &amp; Enterocutaneous Fistulae</brief_title>
  <official_title>A Pilot Study: Evaluating the Safety and Feasibility of Using Autologous Adipose-Derived Stromal Vascular Fraction (SVF) for the Treatment of Aerodigestive &amp; Enterocutaneous Fistulae in Adults</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mayo Clinic</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Determine safety and feasibility of using institutionally prepared autologous, uncultured SVF&#xD;
      on patients with aerodigestive and enterocutaneous fistulae secondary to malignancy, trauma&#xD;
      or surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary aim of this pilot study is to evaluate the feasibility, time, cost, safety,&#xD;
      limitations, and efficacy of the use of institutionally processed SVF for management and&#xD;
      closure of aero-digestive and enterocutaneous fistulae. This pilot study would help identify&#xD;
      design issues and the potential success of fistulae closure by the means of autologous SVF&#xD;
      administration before a full-scale trial is performed.&#xD;
&#xD;
      A secondary aim is the closure of aero-digestive and enterocutaneous fistulae along with&#xD;
      characteristics such as size, etiology, recurrence, localization, and the association of&#xD;
      these factors withoutcome after SVF administration. The SVF quantification, characterization&#xD;
      and differentiation in vitro will be described.&#xD;
&#xD;
      This process will help identify the type of fistulae that are susceptible to closure with&#xD;
      human cell therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Study closed due to lack of patient enrollment.&#xD;
  </why_stopped>
  <start_date type="Anticipated">February 2021</start_date>
  <completion_date type="Anticipated">February 2028</completion_date>
  <primary_completion_date type="Anticipated">February 2027</primary_completion_date>
  <phase>Phase 1</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>Assessment of Adverse Events from a single dose of autologous stromal vascular fraction (SVF) applied endoscopically into aerodigestive fistulae or enterocutaneous fistula [Safety and Tolerability].</measure>
    <time_frame>5 Years</time_frame>
    <description>Documentation of signs of adverse reactions from intravascular application of TISEEL, including: intravascular coagulation, thromboembolic events and acute hypersensitivity reactions. Documentation of signs of increased fistula size and/or aggravation of symptoms associated with fistulous tract, including: paroxysmal cough, dysphagia, wheezing, abdominal distention, chest pain, dyspnea, pneumonia.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessment of Adverse Events from liposuction procedure [Safety and Tolerability].</measure>
    <time_frame>5 Years</time_frame>
    <description>Signs of adverse reactions to the lipoaspiration procedure, including: allergic reaction to Hunstad solution, infection at the puncture wound site or risk of bleeding at the puncture wound site.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assessment of efficacy of Stromal Vascular Fraction's (SVF)'s ability to improve the success of surgical repair by fistulous tract reduction and/or closure.</measure>
    <time_frame>16 weeks</time_frame>
    <description>Measurement and photography of the fistula in endoscopic/bronchoscopic evaluation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of efficacy of Stromal Vascular Fraction's (SVF)'s ability to improve the success of surgical repair in reducing cardinal symptoms.</measure>
    <time_frame>5 Years</time_frame>
    <description>Documentation of reduction of cardinal symptoms by history and physical examination.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of efficacy of Stromal Vascular Fraction's (SVF)'s ability to prevent recurrence of aerodigestive fistulae or enterocutaneous fistulae.</measure>
    <time_frame>5 Years</time_frame>
    <description>Documentation of fistula recurrence by long term follow-up.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Tracheoesopharyngeal Fistula</condition>
  <condition>Bronchoesophageal Fistula</condition>
  <condition>Tracheoesophageal Fistula</condition>
  <arm_group>
    <arm_group_label>Single Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SVF (Stromal Vascular Fraction)</intervention_name>
    <description>The stromal vascular fraction (SVF), isolated when fresh lipoaspirates are enzymatically digested with a collagenase, contains a heterogeneous cellular and extracellular milieu. SVF is an aqueous fraction, consisting of endothelial cells and their precursors, macrophages, smooth muscle cells, lymphocytes, pericytes, pre-adipocytes and actual AMSCs.</description>
    <arm_group_label>Single Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults ≥ 18 years old&#xD;
&#xD;
          -  Adults ≤ 90 years old&#xD;
&#xD;
          -  Fistula or sinus tract opening size between 2 mm and 15 mm in diameter (as measured by&#xD;
             comparing its size with the open mouth of a biopsy forceps)&#xD;
&#xD;
          -  Inpatient or outpatient setting&#xD;
&#xD;
          -  Recurrent or de novo fistulas or sinus tracts&#xD;
&#xD;
          -  A prior diagnosis of ADF OR ECF in which the standard therapy has failed or is not&#xD;
             applicable&#xD;
&#xD;
          -  Fistula or sinus tract location may include:&#xD;
&#xD;
          -  Tracheopharyngeal&#xD;
&#xD;
          -  Tracheoesophageal&#xD;
&#xD;
          -  Bronchoesophageal&#xD;
&#xD;
          -  Gastric, duodenal, jejunal, ileal, colonic or anastomotic -communicating to the skin&#xD;
             (cutaneous)&#xD;
&#xD;
          -  Esophogealgastric anastomosis&#xD;
&#xD;
          -  Mediastinal anastomotic leak&#xD;
&#xD;
          -  Fistula etiology may include:&#xD;
&#xD;
          -  Secondary to previous malignancy with complete remission&#xD;
&#xD;
          -  Secondary to radiotherapy as long as complete remission for 5 years has been achieved&#xD;
             and documented&#xD;
&#xD;
          -  Congenital with or without previous treatment&#xD;
&#xD;
          -  Secondary to surgical interventions or endoscopic therapies such as dilation and&#xD;
             esophageal manipulation&#xD;
&#xD;
          -  Post prolonged tracheal intubation&#xD;
&#xD;
          -  Secondary to inflammatory bowel disease&#xD;
&#xD;
          -  Secondary to foreign body ingestion&#xD;
&#xD;
          -  Secondary to thoracic trauma/crush injuries&#xD;
&#xD;
          -  Secondary to caustic ingestion&#xD;
&#xD;
          -  Secondary to pneumonectomy or mechanical ventilation&#xD;
&#xD;
          -  Esophagomalacia&#xD;
&#xD;
          -  The ability of subjects to give appropriate consent or have an appropriate&#xD;
             representative available to do so&#xD;
&#xD;
          -  The ability of subjects to return for follow up endoscopic assessment as established.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  Exposure to any investigational drug or procedure within 3 months prior to study&#xD;
             entry.&#xD;
&#xD;
          -  Patients with allergy to fibrin glue (TISSEEL) or anesthetics&#xD;
&#xD;
          -  Patients with active/ongoing malignancy such as esophageal, lung, tracheal, thyroid,&#xD;
             oropharyngeal or gastric cancer&#xD;
&#xD;
          -  Patients on active regimen of chemotherapy&#xD;
&#xD;
          -  Patients receiving radiation&#xD;
&#xD;
          -  Diabetics with poor glucose metabolic control exhibited by an HbA1c &gt; 9&#xD;
&#xD;
          -  If there is evidence, in endoscopy, of dysplastic-appearing mucosa such as Barrett's&#xD;
             dysplasia near the fistula or sinus tracts, this will be excluded. Patients that&#xD;
             require surgical intervention at the fistula or sinus tract area for any reason&#xD;
&#xD;
          -  BMI of &lt;16 (may difficult lipoaspiration procedure)&#xD;
&#xD;
          -  Women who are pregnant or nursing or women of childbearing potential who are unwilling&#xD;
             to maintain contraceptive therapy for the duration of the study&#xD;
&#xD;
          -  Clinical signs of respiratory tract or pleuro-pulmonary infections&#xD;
&#xD;
          -  Prolonged (&gt; 6 months) use of steroids&#xD;
&#xD;
          -  Patients with fistulae or sinus tracts &gt;15mm&#xD;
&#xD;
          -  Drug or alcohol dependence&#xD;
&#xD;
          -  Active infectious disease positive for HIV, HTLV, HBV, HCV, CMV (IgM &gt; IgG) and/or&#xD;
             syphilis&#xD;
&#xD;
          -  End of life&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bhaumik Brahmbhatt</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <link>
    <url>https://www.mayo.edu/research/clinical-trials</url>
    <description>Mayo Clinic Clinical Trials</description>
  </link>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>November 21, 2018</study_first_submitted>
  <study_first_submitted_qc>December 31, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">January 3, 2019</study_first_posted>
  <last_update_submitted>April 4, 2023</last_update_submitted>
  <last_update_submitted_qc>April 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Bhaumik Brahmbhatt</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>Intestinal Fistula</mesh_term>
    <mesh_term>Tracheoesophageal Fistula</mesh_term>
    <mesh_term>Fistula</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>September 18, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/60/NCT03792360/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>September 27, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/60/NCT03792360/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03792360
org study id: 17-003774
nct id: NCT03792360
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Determine safety and feasibility of using institutionally prepared autologous, uncultured SVF
      on patients with aerodigestive and enterocutaneous fistulae secondary to malignancy, trauma
      or surgery.
The primary aim of this pilot study is to evaluate the feasibility, time, cost, safety,
      limitations, and efficacy of the use of institutionally processed SVF for management and
      closure of aero-digestive and enterocutaneous fistulae. This pilot study would help identify
      design issues and the potential success of fistulae closure by the means of autologous SVF
      administration before a full-scale trial is performed.

      A secondary aim is the closure of aero-digestive and enterocutaneous fistulae along with
      characteristics such as size, etiology, recurrence, localization, and the association of
      these factors withoutcome after SVF administration. The SVF quantification, characterization
      and differentiation in vitro will be described.

      This process will help identify the type of fistulae that are susceptible to closure with
      human cell therapy.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Assessment of Adverse Events from a single dose of autologous stromal vascular fraction (SVF) applied endoscopically into aerodigestive fistulae or enterocutaneous fistula [Safety and Tolerability].
time frame: 5 Years
description: Documentation of signs of adverse reactions from intravascular application of TISEEL, including: intravascular coagulation, thromboembolic events and acute hypersensitivity reactions. Documentation of signs of increased fistula size and/or aggravation of symptoms associated with fistulous tract, including: paroxysmal cough, dysphagia, wheezing, abdominal distention, chest pain, dyspnea, pneumonia.
measure: Assessment of Adverse Events from liposuction procedure [Safety and Tolerability].
time frame: 5 Years
description: Signs of adverse reactions to the lipoaspiration procedure, including: allergic reaction to Hunstad solution, infection at the puncture wound site or risk of bleeding at the puncture wound site.
measure: Assessment of efficacy of Stromal Vascular Fraction's (SVF)'s ability to improve the success of surgical repair by fistulous tract reduction and/or closure.
time frame: 16 weeks
description: Measurement and photography of the fistula in endoscopic/bronchoscopic evaluation.
measure: Assessment of efficacy of Stromal Vascular Fraction's (SVF)'s ability to improve the success of surgical repair in reducing cardinal symptoms.
time frame: 5 Years
description: Documentation of reduction of cardinal symptoms by history and physical examination.
measure: Assessment of efficacy of Stromal Vascular Fraction's (SVF)'s ability to prevent recurrence of aerodigestive fistulae or enterocutaneous fistulae.
time frame: 5 Years
description: Documentation of fistula recurrence by long term follow-up.
arm group label: Single Arm
arm group type: Experimental
intervention type: Drug
intervention name: SVF (Stromal Vascular Fraction)
description: The stromal vascular fraction (SVF), isolated when fresh lipoaspirates are enzymatically digested with a collagenase, contains a heterogeneous cellular and extracellular milieu. SVF is an aqueous fraction, consisting of endothelial cells and their precursors, macrophages, smooth muscle cells, lymphocytes, pericytes, pre-adipocytes and actual AMSCs.
arm group label: Single Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
last name: Bhaumik Brahmbhatt
role: Principal Investigator
affiliation: Mayo Clinic
country: United States
url: https://www.mayo.edu/research/clinical-trials
description: Mayo Clinic Clinical Trials
responsible party type: Principal Investigator
investigator affiliation: Mayo Clinic
investigator full name: Bhaumik Brahmbhatt
investigator title: Principal Investigator
mesh term: Intestinal Fistula
mesh term: Tracheoesophageal Fistula
mesh term: Fistula
sharing ipd: No
provided document: 
provided document: 