<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/NCT01673789</url>
  </required_header>
  <id_info>
    <org_study_id>2012-TH01</org_study_id>
    <nct_id>NCT01673789</nct_id>
  </id_info>
  <brief_title>Stem Cell Educator Therapy in Alopecia Areata</brief_title>
  <official_title>Phase 1/Phase 2 Study of Stem Cell Educator Therapy in Alopecia Areata</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Throne Biotechnologies Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The First Hospital of Hebei Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Throne Biotechnologies Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Alopecia Areata (AA) is one of the most common T cell-mediated autoimmune diseases, leading&#xD;
      to the chronic and relapsing hair loss. The prevalence of AA worldwide is 0.1 to 0.2%,&#xD;
      affecting an estimated 5.3 million people in the United States. To date, the clinical&#xD;
      therapies are limited and disappointed for the treatment of AA. Alternative approaches are&#xD;
      needed. Increasing evidence demonstrates that stem cells possess the function of immune&#xD;
      modulation. We established the Stem Cell Educator therapy by using cord blood-derived&#xD;
      multipotent stem cells (CB-SCs)(Zhao Y, et al. BMC Medicine 2012). A closed-loop system that&#xD;
      circulates a patient's blood through a blood cell separator, briefly co-cultures the&#xD;
      patient's lymphocytes with adherent CB-SCs in vitro, and returns the educated lymphocytes&#xD;
      (but not the CB-SCs) to the patient's circulation. Our clinical trial reveals that a single&#xD;
      treatment with the Stem Cell Educator provides lasting reversal of autoimmunity that allows&#xD;
      regeneration of islet beta cells and improvement of metabolic control in subjects with&#xD;
      long-standing type 1 diabetes (T1D), which is another most common T cell-mediated autoimmune&#xD;
      disorder in the United States. Here, we develop and explore the therapeutic effectiveness of&#xD;
      Stem Cell Educator therapy in AA patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A 16-gauge IV needle is placed in the left (or right) median cubital vein, and the patient's&#xD;
      blood is passed through a Blood Cell Separator MCS+ (Haemonetics®, Braintree, MA) at 35&#xD;
      mL/min for 6 to 7 hours to isolate lymphocytes in accordance with the manufacturer's&#xD;
      recommended protocol. The collected lymphocytes are transferred into the device for exposure&#xD;
      to allogeneic CB-SCs (or process control without CB-SCs), and other blood components are&#xD;
      returned to the patient. After 2 to 3 hours in the device, lymphocytes are returned to the&#xD;
      patient's circulation via a dorsal vein in the hand under gravity flow control (2 to 3&#xD;
      mL/min) with physiological saline. Approximately 10,000 mL of blood is processed during the&#xD;
      procedure resulting in approximately two repeated educations for the lymphocyte fraction.&#xD;
      Patients are hospitalized for two days to monitor temperature and conduct routine laboratory&#xD;
      blood tests for adverse reactions following treatment. Follow-up visits are scheduled 4, 12,&#xD;
      24, 40, and 54 weeks after treatment for clinical assessments and laboratory tests&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>August 2012</start_date>
  <completion_date type="Anticipated">July 2013</completion_date>
  <primary_completion_date type="Anticipated">July 2013</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>Feasibility and efficacy of Stem Cell Educator therapy in AA</measure>
    <time_frame>1 year</time_frame>
    <description>The primary study end points are 1) feasibility of the Stem Cell Educator therapy in AA, 2) preliminary evaluation of the efficacy of the therapy for improving hire grow through a year.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The efficacy of Stem Cell Educator therapy in modulating autoimmunity</measure>
    <time_frame>1 year</time_frame>
    <description>The secondary study end point was evidence of the efficacy of the therapy in modulating autoimmunity. Baseline blood samples are collected prior to Stem Cell Educator therapy.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Alopecia Areata</condition>
  <arm_group>
    <arm_group_label>Stem Cell Educator</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The collected lymphocytes are transferred into the device for exposure to CB-SCs, and other blood components are automatically returned to the patient. The Stem Cell Educator functions as part of a closed-loop system that circulates a patient's blood through a blood cell separator, briefly co-cultures the patient's lymphocytes with CB-SCs in vitro, and returns the educated lymphocytes to the patient's circulation. CB-SCs tightly attached to interior surfaces in the device, and only the CB-SC-educated autologous lymphocytes are returned to the subjects. The Stem Cell Educator therapy requires only two venipunctures with minimal pain, and does not introduce stem cells or reagents into patients.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Stem Cell Educator</intervention_name>
    <description>For the treatment, commonly the left (or right) median cubital vein, a patient's blood is passed through a Blood Cell Separator that isolates the lymphocytes from the blood according to the recommended protocol by manufacture; consequently, the collected lymphocytes were transferred into the Stem Cell Educator and treated by CB-SC; after that, the educated cells return the blood back to the patient via a dorsal vein of hand. During the MCS+ collection, the whole blood flow rate was maintained at 35 mL/min. The whole procedure was scheduled for 8 ~ 9 hrs.</description>
    <arm_group_label>Stem Cell Educator</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients are screened for enrollment in the study if both clinical signs and&#xD;
             laboratory tests meet the diagnosis standards recommended by the National Alopecia&#xD;
             Areata Foundation (www.naaf.org).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Exclusion criteria are any clinically significant diseases in liver, kidney, and&#xD;
             heart. Additional exclusion criteria are no pregnancy, no immunosuppressive&#xD;
             medication, no viral diseases or diseases associated with immunodeficiency.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yong Zhao, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Throne Biotechnologies Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The First Hospital of Hebei Medical University</name>
      <address>
        <city>Shijiazhuang</city>
        <state>Hebei</state>
        <zip>050031</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yanjia Li, MD</last_name>
      <phone>86 311 85917311</phone>
      <email>liyanjia2008@gmail.com</email>
    </contact>
    <investigator>
      <last_name>Yanjia Li, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <link>
    <url>http://www.tianhecell.com</url>
    <description>Tianhe Stem Cell Biotechnologies Inc.</description>
  </link>
  <reference>
    <citation>Zhao Y, Jiang Z, Zhao T, Ye M, Hu C, Yin Z, Li H, Zhang Y, Diao Y, Li Y, Chen Y, Sun X, Fisk MB, Skidgel R, Holterman M, Prabhakar B, Mazzone T. Reversal of type 1 diabetes via islet beta cell regeneration following immune modulation by cord blood-derived multipotent stem cells. BMC Med. 2012 Jan 10;10:3. doi: 10.1186/1741-7015-10-3.</citation>
    <PMID>22233865</PMID>
  </reference>
  <reference>
    <citation>Zhao Y. Stem cell educator therapy and induction of immune balance. Curr Diab Rep. 2012 Oct;12(5):517-23. doi: 10.1007/s11892-012-0308-1.</citation>
    <PMID>22833322</PMID>
  </reference>
  <verification_date>August 2012</verification_date>
  <study_first_submitted>August 21, 2012</study_first_submitted>
  <study_first_submitted_qc>August 23, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 28, 2012</study_first_posted>
  <last_update_submitted>August 23, 2012</last_update_submitted>
  <last_update_submitted_qc>August 23, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 28, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Stem Cell Educator</keyword>
  <keyword>Cord blood stem cells</keyword>
  <keyword>Immune modulation</keyword>
  <keyword>Alopecia Areata</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alopecia</mesh_term>
    <mesh_term>Alopecia Areata</mesh_term>
  </condition_browse>
  <pending_results>
    <submitted>February 2, 2019</submitted>
    <returned>May 2, 2019</returned>
    <submitted>June 3, 2019</submitted>
    <returned>August 1, 2019</returned>
  </pending_results>
  <!-- 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/NCT01673789
org study id: 2012-TH01
nct id: NCT01673789
lead sponsor: 
collaborator: 
has dmc: Yes
Alopecia Areata (AA) is one of the most common T cell-mediated autoimmune diseases, leading
      to the chronic and relapsing hair loss. The prevalence of AA worldwide is 0.1 to 0.2%,
      affecting an estimated 5.3 million people in the United States. To date, the clinical
      therapies are limited and disappointed for the treatment of AA. Alternative approaches are
      needed. Increasing evidence demonstrates that stem cells possess the function of immune
      modulation. We established the Stem Cell Educator therapy by using cord blood-derived
      multipotent stem cells (CB-SCs)(Zhao Y, et al. BMC Medicine 2012). A closed-loop system that
      circulates a patient's blood through a blood cell separator, briefly co-cultures the
      patient's lymphocytes with adherent CB-SCs in vitro, and returns the educated lymphocytes
      (but not the CB-SCs) to the patient's circulation. Our clinical trial reveals that a single
      treatment with the Stem Cell Educator provides lasting reversal of autoimmunity that allows
      regeneration of islet beta cells and improvement of metabolic control in subjects with
      long-standing type 1 diabetes (T1D), which is another most common T cell-mediated autoimmune
      disorder in the United States. Here, we develop and explore the therapeutic effectiveness of
      Stem Cell Educator therapy in AA patients.
A 16-gauge IV needle is placed in the left (or right) median cubital vein, and the patient's
      blood is passed through a Blood Cell Separator MCS+ (Haemonetics®, Braintree, MA) at 35
      mL/min for 6 to 7 hours to isolate lymphocytes in accordance with the manufacturer's
      recommended protocol. The collected lymphocytes are transferred into the device for exposure
      to allogeneic CB-SCs (or process control without CB-SCs), and other blood components are
      returned to the patient. After 2 to 3 hours in the device, lymphocytes are returned to the
      patient's circulation via a dorsal vein in the hand under gravity flow control (2 to 3
      mL/min) with physiological saline. Approximately 10,000 mL of blood is processed during the
      procedure resulting in approximately two repeated educations for the lymphocyte fraction.
      Patients are hospitalized for two days to monitor temperature and conduct routine laboratory
      blood tests for adverse reactions following treatment. Follow-up visits are scheduled 4, 12,
      24, 40, and 54 weeks after treatment for clinical assessments and laboratory tests
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Feasibility and efficacy of Stem Cell Educator therapy in AA
time frame: 1 year
description: The primary study end points are 1) feasibility of the Stem Cell Educator therapy in AA, 2) preliminary evaluation of the efficacy of the therapy for improving hire grow through a year.
measure: The efficacy of Stem Cell Educator therapy in modulating autoimmunity
time frame: 1 year
description: The secondary study end point was evidence of the efficacy of the therapy in modulating autoimmunity. Baseline blood samples are collected prior to Stem Cell Educator therapy.
arm group label: Stem Cell Educator
arm group type: Experimental
description: The collected lymphocytes are transferred into the device for exposure to CB-SCs, and other blood components are automatically returned to the patient. The Stem Cell Educator functions as part of a closed-loop system that circulates a patient's blood through a blood cell separator, briefly co-cultures the patient's lymphocytes with CB-SCs in vitro, and returns the educated lymphocytes to the patient's circulation. CB-SCs tightly attached to interior surfaces in the device, and only the CB-SC-educated autologous lymphocytes are returned to the subjects. The Stem Cell Educator therapy requires only two venipunctures with minimal pain, and does not introduce stem cells or reagents into patients.
intervention type: Device
intervention name: Stem Cell Educator
description: For the treatment, commonly the left (or right) median cubital vein, a patient's blood is passed through a Blood Cell Separator that isolates the lymphocytes from the blood according to the recommended protocol by manufacture; consequently, the collected lymphocytes were transferred into the Stem Cell Educator and treated by CB-SC; after that, the educated cells return the blood back to the patient via a dorsal vein of hand. During the MCS+ collection, the whole blood flow rate was maintained at 35 mL/min. The whole procedure was scheduled for 8 ~ 9 hrs.
arm group label: Stem Cell Educator
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Yong Zhao, MD, PhD
role: Study Chair
affiliation: Throne Biotechnologies Inc.
facility: 
status: Recruiting
contact: 
investigator: 
country: China
url: http://www.tianhecell.com
description: Tianhe Stem Cell Biotechnologies Inc.
citation: Zhao Y, Jiang Z, Zhao T, Ye M, Hu C, Yin Z, Li H, Zhang Y, Diao Y, Li Y, Chen Y, Sun X, Fisk MB, Skidgel R, Holterman M, Prabhakar B, Mazzone T. Reversal of type 1 diabetes via islet beta cell regeneration following immune modulation by cord blood-derived multipotent stem cells. BMC Med. 2012 Jan 10;10:3. doi: 10.1186/1741-7015-10-3.
PMID: 22233865
citation: Zhao Y. Stem cell educator therapy and induction of immune balance. Curr Diab Rep. 2012 Oct;12(5):517-23. doi: 10.1007/s11892-012-0308-1.
PMID: 22833322
responsible party type: Sponsor
mesh term: Alopecia
mesh term: Alopecia Areata
submitted: February 2, 2019
returned: May 2, 2019
submitted: June 3, 2019
returned: August 1, 2019