<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/NCT03021681</url>
  </required_header>
  <id_info>
    <org_study_id>Huaian1PH2</org_study_id>
    <nct_id>NCT03021681</nct_id>
  </id_info>
  <brief_title>An Exploratory Study on the Treatment of Chronic Obstructive Pulmonary Disease With Autologous Bronchial Basal Cell Transplantation</brief_title>
  <official_title>Huai'an First People 's Hospital,Nanjing Medical University</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Huai'an No.1 People's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Regend Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Huai'an No.1 People's Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Chronic obstructive pulmonary disease(COPD)is characterized by recurrent cough, expectoration&#xD;
      and asthma, and eventually develop chronic pulmonary heart disease ,chronic respiratory&#xD;
      failure and even death. The current clinical treatments for these patients are symptomatic&#xD;
      treatment cannot solve the problem of the damaged lung structure fundamentally. Recent&#xD;
      studies show that bronchial basement the layer of cells is a kind of cells in the bronchial&#xD;
      epithelial basal layer position, the specific expression of Krt5 antigen with the&#xD;
      regeneration and repair of lung function , these cells have the activity similar to adult&#xD;
      tissue stem cells. Its division and migration are more active and can continue to produce new&#xD;
      cells to complement the death of other types of epithelial cells with functional plasticity&#xD;
      which can be used to direct repair the bronchial and alveolar structures. It has been proved&#xD;
      that bronchial basal cell transplantation can repair the damaged lungs of experimental&#xD;
      animals . The bronchial basal cells from autologous tissue, so there is no immune rejection&#xD;
      problem. Also because the bronchial basal cells derived from adult tissues which is a part of&#xD;
      the body, so there is no risk of a tumor (in animal experiments, In animal experiments,&#xD;
      bronchial basal cells transtracheal input 100 times in human dose still no tumor formation).&#xD;
      In the early stage, patients with COPD (2 cases), bronchiectasis (2 cases) and interstitial&#xD;
      lung disease (1 case) received the treatment, and the overall effect was good. Diseases were&#xD;
      alleviated and recovered to some different extend.The study was to brush bronchial basal&#xD;
      cells through fiberbronchoscopy in COPD patients and cultured in vitro, and then through the&#xD;
      bronchoscope transfusion to the lesion site. To preliminary evaluate the efficacy and safety&#xD;
      of autologous bronchial basal cells in the treatment of chronic obstructive pulmonary&#xD;
      disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Between November 2016 and November 2019, the investigators initially recruited 20 with stable&#xD;
      COPD patients. Primary evaluations including medical history, physical examination,&#xD;
      anthropometric data, blood routine, blood biochemistry, blood coagulation,&#xD;
      electrocardiogram,high resolution chest CT, arterial blood gas, pulmonary function test,6-min&#xD;
      walking test(6MWT),modified medical research council(MMRC),St George's respiratory&#xD;
      questionnaire(SGRQ). After initial evaluation, the investigators obtained extraction&#xD;
      bronchial basal cells micro tissue from 3~4 grade bronchus to by mean of fiberbronchoscopy,&#xD;
      then purified and selectively amplified bronchial basal cells to reserve .The basal layer&#xD;
      cell culture system for our partners (Regend Therapeutics) patented technology using culture&#xD;
      medium containing special combination of growth factors and composite materials to simulated&#xD;
      composite basal layer environment and can selectively amplified bronchial basal cells, while&#xD;
      other types of mature epithelial cells and fibroblasts could not grow naturally. After a&#xD;
      period of time, the basal lamina of the bronchial epithelial cells can be stored in the&#xD;
      liquid nitrogen cell bank for a long time. Before applied to the patient, bronchial basal&#xD;
      cells need to go through a series of strict examination. Then, bronchoscopy was performed&#xD;
      again and the bronchial basal lamina suspension was injected directly into the lesion site .&#xD;
      Estimate the change of respiratory function(symptoms, signs, chest CT, pulmonary function,&#xD;
      the 6 minute walk test, MMRC, SGRQ etc) and serum index in third days , first months, third&#xD;
      months, sixth months and first years of the follow-up after treatment respectively, to&#xD;
      evaluate the safety and efficiency of autologous bronchial basal cells for treatment of COPD&#xD;
      .&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2016</start_date>
  <completion_date type="Actual">November 2021</completion_date>
  <primary_completion_date type="Actual">November 2021</primary_completion_date>
  <phase>N/A</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>forced expiratory volume in one second(FEV1)</measure>
    <time_frame>24 months</time_frame>
    <description>as the severity of chronic obstructive pulmonary disease(COPD)estimated by pulmonary function</description>
  </primary_outcome>
  <primary_outcome>
    <measure>chest high-resolution computed tomography</measure>
    <time_frame>24 months</time_frame>
    <description>as the severity of lung hyperinflation estimated by radiological</description>
  </primary_outcome>
  <primary_outcome>
    <measure>arterial blood gas</measure>
    <time_frame>24 months</time_frame>
    <description>to assess the level of hypoxemia and hypercapnia in chronic obstructive pulmonary disease(COPD) patients</description>
  </primary_outcome>
  <primary_outcome>
    <measure>6MWT</measure>
    <time_frame>24 months</time_frame>
    <description>6 min walking test, to evaluate the exercise function in patients with moderate and severe pulmonary heart diseases</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>forced vital capacity(FVC)</measure>
    <time_frame>24 months</time_frame>
    <description>an index of pulmonary function in chronic obstructive pulmonary disease(COPD) patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MMRC</measure>
    <time_frame>24 months</time_frame>
    <description>an index to evaluate the lever of dyspnea</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>SGRQ</measure>
    <time_frame>24 months</time_frame>
    <description>a questionnaire to assess the influence of chronic airflow restriction on the quality of life, including symptoms, activities and daily life affected by diseases</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Cell Transplantation</condition>
  <arm_group>
    <arm_group_label>COPD group(self control)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Prior treatment:20 stable COPD patients were enrolled,estimated the respiratory function and serum index Intervention:autologous bronchial basal cell transplantation After treatment:Estimate the change of respiratory function and serum index in third days , first months, third months, sixth months and first years of the follow-up after treatment respectively</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>autologous bronchial basal cell transplantation</intervention_name>
    <description>the investigators obtained extraction bronchial basal cells micro tissue from 3~4 grade bronchus, then purified and selectively amplified bronchial basal cells to reserve . After a period of time, the basal lamina of the bronchial epithelial cells can be stored in the liquid nitrogen cell bank for a long time. Before applied to the patient, bronchial basal cells need to go through a series of strict examination. Then, bronchoscopy was performed again and the bronchial basal lamina suspension was injected directly into the lesion site .</description>
    <arm_group_label>COPD group(self control)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. aged between 18 to 70 years&#xD;
&#xD;
          2. according to the guideline criteria, the diagnosis of COPD:&#xD;
&#xD;
             ①There is a chronic cough, sputum or gas breathing symptoms such as promoting&#xD;
&#xD;
             ②Pulmonary function tests showed airflow limitation(FEV1&lt;80% predicted&#xD;
             value，FEV1/FVC&lt;0.7)&#xD;
&#xD;
          3. CT imaging and hematological examination excluded other lung diseases.&#xD;
&#xD;
          4. stable disease for more than 2 weeks&#xD;
&#xD;
          5. patients who were able to tolerate fiberoptic bronchoscopy&#xD;
&#xD;
          6. to sign the informed consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. women who are pregnant, nursing or not taking effective contraception&#xD;
&#xD;
          2. syphilis, HIV antibody positive person&#xD;
&#xD;
          3. there is a history of alcohol or illicit drug abuse&#xD;
&#xD;
          4. patients who had received any other clinical trial within the first 3 months&#xD;
&#xD;
          5. poor compliance, it is difficult to complete the study&#xD;
&#xD;
          6. researchers believe there may be any increase in the risk of the subject or any&#xD;
             interference with the clinical trial&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wei Zuo, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Regend Therapeutics,Suzhou Industry Park,Suzhou,CHINA</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Huai'an First People's Hospital</name>
      <address>
        <city>Huai'an</city>
        <state>Jiangsu</state>
        <zip>223300</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Zuo W, Zhang T, Wu DZ, Guan SP, Liew AA, Yamamoto Y, Wang X, Lim SJ, Vincent M, Lessard M, Crum CP, Xian W, McKeon F. p63(+)Krt5(+) distal airway stem cells are essential for lung regeneration. Nature. 2015 Jan 29;517(7536):616-20. doi: 10.1038/nature13903. Epub 2014 Nov 12.</citation>
    <PMID>25383540</PMID>
  </reference>
  <reference>
    <citation>Kumar PA, Hu Y, Yamamoto Y, Hoe NB, Wei TS, Mu D, Sun Y, Joo LS, Dagher R, Zielonka EM, Wang de Y, Lim B, Chow VT, Crum CP, Xian W, McKeon F. Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection. Cell. 2011 Oct 28;147(3):525-38. doi: 10.1016/j.cell.2011.10.001.</citation>
    <PMID>22036562</PMID>
  </reference>
  <reference>
    <citation>Rock JR, Randell SH, Hogan BL. Airway basal stem cells: a perspective on their roles in epithelial homeostasis and remodeling. Dis Model Mech. 2010 Sep-Oct;3(9-10):545-56. doi: 10.1242/dmm.006031. Epub 2010 Aug 10.</citation>
    <PMID>20699479</PMID>
  </reference>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>January 12, 2017</study_first_submitted>
  <study_first_submitted_qc>January 13, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 16, 2017</study_first_posted>
  <last_update_submitted>March 28, 2022</last_update_submitted>
  <last_update_submitted_qc>March 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 29, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Huai'an No.1 People's Hospital</investigator_affiliation>
    <investigator_full_name>ZiLi Meng</investigator_full_name>
    <investigator_title>Director of respiratory Medicine in Huai'an No.1 People's Hospital</investigator_title>
  </responsible_party>
  <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/NCT03021681
org study id: Huaian1PH2
nct id: NCT03021681
lead sponsor: 
collaborator: 
has dmc: No
Chronic obstructive pulmonary disease(COPD)is characterized by recurrent cough, expectoration
      and asthma, and eventually develop chronic pulmonary heart disease ,chronic respiratory
      failure and even death. The current clinical treatments for these patients are symptomatic
      treatment cannot solve the problem of the damaged lung structure fundamentally. Recent
      studies show that bronchial basement the layer of cells is a kind of cells in the bronchial
      epithelial basal layer position, the specific expression of Krt5 antigen with the
      regeneration and repair of lung function , these cells have the activity similar to adult
      tissue stem cells. Its division and migration are more active and can continue to produce new
      cells to complement the death of other types of epithelial cells with functional plasticity
      which can be used to direct repair the bronchial and alveolar structures. It has been proved
      that bronchial basal cell transplantation can repair the damaged lungs of experimental
      animals . The bronchial basal cells from autologous tissue, so there is no immune rejection
      problem. Also because the bronchial basal cells derived from adult tissues which is a part of
      the body, so there is no risk of a tumor (in animal experiments, In animal experiments,
      bronchial basal cells transtracheal input 100 times in human dose still no tumor formation).
      In the early stage, patients with COPD (2 cases), bronchiectasis (2 cases) and interstitial
      lung disease (1 case) received the treatment, and the overall effect was good. Diseases were
      alleviated and recovered to some different extend.The study was to brush bronchial basal
      cells through fiberbronchoscopy in COPD patients and cultured in vitro, and then through the
      bronchoscope transfusion to the lesion site. To preliminary evaluate the efficacy and safety
      of autologous bronchial basal cells in the treatment of chronic obstructive pulmonary
      disease.
Between November 2016 and November 2019, the investigators initially recruited 20 with stable
      COPD patients. Primary evaluations including medical history, physical examination,
      anthropometric data, blood routine, blood biochemistry, blood coagulation,
      electrocardiogram,high resolution chest CT, arterial blood gas, pulmonary function test,6-min
      walking test(6MWT),modified medical research council(MMRC),St George's respiratory
      questionnaire(SGRQ). After initial evaluation, the investigators obtained extraction
      bronchial basal cells micro tissue from 3~4 grade bronchus to by mean of fiberbronchoscopy,
      then purified and selectively amplified bronchial basal cells to reserve .The basal layer
      cell culture system for our partners (Regend Therapeutics) patented technology using culture
      medium containing special combination of growth factors and composite materials to simulated
      composite basal layer environment and can selectively amplified bronchial basal cells, while
      other types of mature epithelial cells and fibroblasts could not grow naturally. After a
      period of time, the basal lamina of the bronchial epithelial cells can be stored in the
      liquid nitrogen cell bank for a long time. Before applied to the patient, bronchial basal
      cells need to go through a series of strict examination. Then, bronchoscopy was performed
      again and the bronchial basal lamina suspension was injected directly into the lesion site .
      Estimate the change of respiratory function(symptoms, signs, chest CT, pulmonary function,
      the 6 minute walk test, MMRC, SGRQ etc) and serum index in third days , first months, third
      months, sixth months and first years of the follow-up after treatment respectively, to
      evaluate the safety and efficiency of autologous bronchial basal cells for treatment of COPD
      .
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: forced expiratory volume in one second(FEV1)
time frame: 24 months
description: as the severity of chronic obstructive pulmonary disease(COPD)estimated by pulmonary function
measure: chest high-resolution computed tomography
time frame: 24 months
description: as the severity of lung hyperinflation estimated by radiological
measure: arterial blood gas
time frame: 24 months
description: to assess the level of hypoxemia and hypercapnia in chronic obstructive pulmonary disease(COPD) patients
measure: 6MWT
time frame: 24 months
description: 6 min walking test, to evaluate the exercise function in patients with moderate and severe pulmonary heart diseases
measure: forced vital capacity(FVC)
time frame: 24 months
description: an index of pulmonary function in chronic obstructive pulmonary disease(COPD) patients
measure: MMRC
time frame: 24 months
description: an index to evaluate the lever of dyspnea
measure: SGRQ
time frame: 24 months
description: a questionnaire to assess the influence of chronic airflow restriction on the quality of life, including symptoms, activities and daily life affected by diseases
arm group label: COPD group(self control)
arm group type: Other
description: Prior treatment:20 stable COPD patients were enrolled,estimated the respiratory function and serum index Intervention:autologous bronchial basal cell transplantation After treatment:Estimate the change of respiratory function and serum index in third days , first months, third months, sixth months and first years of the follow-up after treatment respectively
intervention type: Other
intervention name: autologous bronchial basal cell transplantation
description: the investigators obtained extraction bronchial basal cells micro tissue from 3~4 grade bronchus, then purified and selectively amplified bronchial basal cells to reserve . After a period of time, the basal lamina of the bronchial epithelial cells can be stored in the liquid nitrogen cell bank for a long time. Before applied to the patient, bronchial basal cells need to go through a series of strict examination. Then, bronchoscopy was performed again and the bronchial basal lamina suspension was injected directly into the lesion site .
arm group label: COPD group(self control)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Wei Zuo, PhD
role: Study Chair
affiliation: Regend Therapeutics,Suzhou Industry Park,Suzhou,CHINA
facility: 
country: China
citation: Zuo W, Zhang T, Wu DZ, Guan SP, Liew AA, Yamamoto Y, Wang X, Lim SJ, Vincent M, Lessard M, Crum CP, Xian W, McKeon F. p63(+)Krt5(+) distal airway stem cells are essential for lung regeneration. Nature. 2015 Jan 29;517(7536):616-20. doi: 10.1038/nature13903. Epub 2014 Nov 12.
PMID: 25383540
citation: Kumar PA, Hu Y, Yamamoto Y, Hoe NB, Wei TS, Mu D, Sun Y, Joo LS, Dagher R, Zielonka EM, Wang de Y, Lim B, Chow VT, Crum CP, Xian W, McKeon F. Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection. Cell. 2011 Oct 28;147(3):525-38. doi: 10.1016/j.cell.2011.10.001.
PMID: 22036562
citation: Rock JR, Randell SH, Hogan BL. Airway basal stem cells: a perspective on their roles in epithelial homeostasis and remodeling. Dis Model Mech. 2010 Sep-Oct;3(9-10):545-56. doi: 10.1242/dmm.006031. Epub 2010 Aug 10.
PMID: 20699479
responsible party type: Principal Investigator
investigator affiliation: Huai'an No.1 People's Hospital
investigator full name: ZiLi Meng
investigator title: Director of respiratory Medicine in Huai'an No.1 People's Hospital
sharing ipd: No