<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/NCT04433104</url>
  </required_header>
  <id_info>
    <org_study_id>VinmecISC1916</org_study_id>
    <nct_id>NCT04433104</nct_id>
  </id_info>
  <brief_title>Umbilical Cord Mesenchymal Stem Cells Transplantation in the Treatment of Chronic Obstructive Pulmonary Disease</brief_title>
  <official_title>Allogeneic Human Umbilical Cord-derived Mesenchymal Stem/Stromal Cells for Chronic Obstructive Pulmonary Disease (COPD): Study Protocol for a Matched Case-control, Phase I/II Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vinmec Research Institute of Stem Cell and Gene Technology</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Vinmec Research Institute of Stem Cell and Gene Technology</source>
  <oversight_info>
    <has_dmc>Yes</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>
      This trial is to investigate the safety and potential therapeutic efficacy of allogeneic&#xD;
      administration of umbilical cord-derived MSCs (UC-MSCs) as a supplementary intervention in&#xD;
      combination with standard COPD medication treatments in patients with moderate-to-severe COPD&#xD;
      based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2019 and Vietnam&#xD;
      Ministry of Health's guidelines&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The aim of this trial is to investigate the safety and potential therapeutic efficacy of&#xD;
      allogeneic administration of umbilical cord-derived MSCs (UC-MSCs) as a supplementary&#xD;
      intervention in combination with standard COPD medication treatments in patients with&#xD;
      moderate-to-severe COPD based on the Global Initiative for Chronic Obstructive Lung Disease&#xD;
      (GOLD) 2019 and Vietnam Ministry of Health's guidelines. This matched case-control phase I/II&#xD;
      trial is conducted at Vinmec Times City International Hospital, Hanoi, Vietnam between June&#xD;
      2020 and December 2021. In this study, 40 patients will be enrolled and assigned into two&#xD;
      age-, gender- and COPD condition-matched groups, including a UC-MSC group and a control&#xD;
      group. Both groups will receive standard COPD medication treatment based on the GOLD 2019&#xD;
      guidelines and the Vietnam Ministry of Health protocol. The UC-MSC group will receive two&#xD;
      doses of thawed UC-MSC product with an intervention interval of 3 months. The primary outcome&#xD;
      measures will include the incidence of prespecified administrationassociated adverse events&#xD;
      (AEs) and serious adverse events (SAEs). The efficacy will be evaluated based on the absolute&#xD;
      changes in the number of admissions, arterial blood gas analysis, lung function and lung&#xD;
      fibrosis via CT scan and chest X-ray. The clinical evaluation will be conducted at baseline&#xD;
      and 3, 6, and 12 months post&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 9, 2020</start_date>
  <completion_date type="Anticipated">December 25, 2021</completion_date>
  <primary_completion_date type="Anticipated">July 30, 2021</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>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse events and serious adverse events</measure>
    <time_frame>up to the 12-month period following treatment</time_frame>
    <description>To assess safety, the number of AEs or SAEs during stem cell administration (72 h) at 3 months, 6 months, and 12 months after discharge will be evaluated</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Quality of Life using Georges Respiratory Questionnaire</measure>
    <time_frame>up to the 12-month period following treatment</time_frame>
    <description>Georges Respiratory Questionnaire has scores range from 0 to 100, with higher scores indicating more limitations</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Chest CT</measure>
    <time_frame>up to the 12-month period following treatment</time_frame>
    <description>Changes of the lung fibrosis on chest CT at 6 months, and 12 months compared with baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>arterial blood gas analysis (pH)</measure>
    <time_frame>up to the 12-month period following treatment</time_frame>
    <description>arterial blood gas analysis (pH)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>arterial blood gas analysis (PaO2)</measure>
    <time_frame>up to the 12-month period following treatment</time_frame>
    <description>arterial blood gas analysis (PaO2)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>arterial blood gas analysis (PaCO2)</measure>
    <time_frame>up to the 12-month period following treatment</time_frame>
    <description>arterial blood gas analysis (PaCO2)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>arterial blood gas analysis (BE)</measure>
    <time_frame>up to the 12-month period following treatment</time_frame>
    <description>arterial blood gas analysis (BE)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>arterial blood gas analysis (HCO3-)</measure>
    <time_frame>up to the 12-month period following treatment</time_frame>
    <description>arterial blood gas analysis (HCO3-)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Respiratory functions (FEV1)</measure>
    <time_frame>up to the 12-month period following treatment</time_frame>
    <description>Respiratory functions (FEV1)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Respiratory functions (FEV1/FVC)</measure>
    <time_frame>up to the 12-month period following treatment</time_frame>
    <description>Respiratory functions (FEV1/FVC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Respiratory functions (VC)</measure>
    <time_frame>up to the 12-month period following treatment</time_frame>
    <description>Respiratory functions (VC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Respiratory functions (TLC)</measure>
    <time_frame>up to the 12-month period following treatment</time_frame>
    <description>Respiratory functions (TLC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Respiratory functions (RV)</measure>
    <time_frame>up to the 12-month period following treatment</time_frame>
    <description>Respiratory functions (RV)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Respiratory functions (DLCO)</measure>
    <time_frame>up to the 12-month period following treatment</time_frame>
    <description>Respiratory functions (DLCO)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Respiratory functions (DLNO/DLCO)</measure>
    <time_frame>up to the 12-month period following treatment</time_frame>
    <description>Respiratory functions (DLNO/DLCO)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>inflammatory response (CRP)</measure>
    <time_frame>up to the 12-month period following treatment</time_frame>
    <description>inflammatory response (CRP)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>inflammatory response (Pro-BNP)</measure>
    <time_frame>up to the 12-month period following treatment</time_frame>
    <description>inflammatory response (Pro-BNP)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>inflammatory response (Troponin-T)</measure>
    <time_frame>up to the 12-month period following treatment</time_frame>
    <description>inflammatory response (Troponin-T)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>cytokine analysis from patients' plasma</measure>
    <time_frame>up to the 12-month period following treatment</time_frame>
    <description>cytokine analysis from patients' plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>modified medical research council</measure>
    <time_frame>up to the 12-month period following treatment</time_frame>
    <description>modified medical research council (mMRC)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>COPD</condition>
  <arm_group>
    <arm_group_label>Treatment (UC-MSC trasnplatation)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 x 10^6 umbilical Cord Mesenchymal Stem Cells per body kg will transplant via the intravenous at baseline, and the second transplantation will be performed 3 months after the first transplantation and combination with Vietnames MOH procedure</description>
  </arm_group>
  <arm_group>
    <arm_group_label>control arm</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>drug therapy according to Vietnamese MOHS procedure</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Umbilical Cord Mesenchymal Stem Cells transplantation</intervention_name>
    <description>Patients assigned to UC-MSC administration groups will receive two administrations at a dose of 1 million cells/kg patient body weight via the IV route with a 3-month intervening interval</description>
    <arm_group_label>Treatment (UC-MSC trasnplatation)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>drug therapy according to Vietnamese MOHS procedure</intervention_name>
    <description>Salbutamol, Terbutaline</description>
    <arm_group_label>Treatment (UC-MSC trasnplatation)</arm_group_label>
    <arm_group_label>control arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosed with COPD with stage B, C, or D according to GOLD 2019.&#xD;
&#xD;
          -  Age between 40-75 years old.&#xD;
&#xD;
          -  Both genders.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Smoker or less than 6 months of smoking cessation time.&#xD;
&#xD;
          -  Asthma and other pulmonary-related diseases and injuries (including lung tuberculosis,&#xD;
             restrictive lung disease, idiopathic pulmonary fibrosis, or lung cancer).&#xD;
&#xD;
          -  Acute and/or active infection.&#xD;
&#xD;
          -  Cancer.&#xD;
&#xD;
          -  Patients with complex cardiovascular diseases (including valvular heart disease,&#xD;
             cardiomyopathy, arrhythmia, congenital heart disease, hypertrophy syndrome).&#xD;
&#xD;
          -  Liver and kidney failure.&#xD;
&#xD;
          -  Pregnancy.&#xD;
&#xD;
          -  Patients with life expectancy less than 6 months due to concomitant illness.&#xD;
&#xD;
          -  Under immunosuppressive treatment within 8 weeks of the first screening visit.&#xD;
&#xD;
          -  Patient diagnosed diabetes with HbA1C&gt;7%&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Duc Minh Hoang, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vinmec Research Institute of Stem Cell and Gene Technology</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Duc Minh Hoang, PhD</last_name>
    <phone>(+84) 909 743 101</phone>
    <email>v.duchm3@vinmec.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Anh Hai Nguyen, MD., PhD</last_name>
    <phone>(+84)968863668</phone>
    <email>haianhnguyenbm@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Vinmec International Hospital Times City</name>
      <address>
        <city>Hà Nội</city>
        <state>Hanoi</state>
        <zip>100000</zip>
        <country>Vietnam</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anh Hai Nguyen, MD, PhD</last_name>
      <phone>(+84)968863668</phone>
      <email>haianhnguyenbm@gmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Vietnam</country>
  </location_countries>
  <results_reference>
    <citation>Ribeiro-Paes JT, Bilaqui A, Greco OT, Ruiz MA, Marcelino MY, Stessuk T, de Faria CA, Lago MR. Unicentric study of cell therapy in chronic obstructive pulmonary disease/pulmonary emphysema. Int J Chron Obstruct Pulmon Dis. 2011 Jan 1;6:63-71. doi: 10.2147/COPD.S15292.</citation>
    <PMID>21311694</PMID>
  </results_reference>
  <results_reference>
    <citation>Stessuk T, Ruiz MA, Greco OT, Bilaqui A, Ribeiro-Paes MJ, Ribeiro-Paes JT. Phase I clinical trial of cell therapy in patients with advanced chronic obstructive pulmonary disease: follow-up of up to 3 years. Rev Bras Hematol Hemoter. 2013;35(5):352-7. doi: 10.5581/1516-8484.20130113.</citation>
    <PMID>24255620</PMID>
  </results_reference>
  <results_reference>
    <citation>Stolk J, Broekman W, Mauad T, Zwaginga JJ, Roelofs H, Fibbe WE, Oostendorp J, Bajema I, Versteegh MI, Taube C, Hiemstra PS. A phase I study for intravenous autologous mesenchymal stromal cell administration to patients with severe emphysema. QJM. 2016 May;109(5):331-6. doi: 10.1093/qjmed/hcw001. Epub 2016 Jan 27.</citation>
    <PMID>26819296</PMID>
  </results_reference>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>June 9, 2020</study_first_submitted>
  <study_first_submitted_qc>June 11, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>April 19, 2021</last_update_submitted>
  <last_update_submitted_qc>April 19, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 21, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COPD</keyword>
  <keyword>umbilical cord mesenchymal stem cells</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</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/NCT04433104
org study id: VinmecISC1916
nct id: NCT04433104
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This trial is to investigate the safety and potential therapeutic efficacy of allogeneic
      administration of umbilical cord-derived MSCs (UC-MSCs) as a supplementary intervention in
      combination with standard COPD medication treatments in patients with moderate-to-severe COPD
      based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2019 and Vietnam
      Ministry of Health's guidelines
The aim of this trial is to investigate the safety and potential therapeutic efficacy of
      allogeneic administration of umbilical cord-derived MSCs (UC-MSCs) as a supplementary
      intervention in combination with standard COPD medication treatments in patients with
      moderate-to-severe COPD based on the Global Initiative for Chronic Obstructive Lung Disease
      (GOLD) 2019 and Vietnam Ministry of Health's guidelines. This matched case-control phase I/II
      trial is conducted at Vinmec Times City International Hospital, Hanoi, Vietnam between June
      2020 and December 2021. In this study, 40 patients will be enrolled and assigned into two
      age-, gender- and COPD condition-matched groups, including a UC-MSC group and a control
      group. Both groups will receive standard COPD medication treatment based on the GOLD 2019
      guidelines and the Vietnam Ministry of Health protocol. The UC-MSC group will receive two
      doses of thawed UC-MSC product with an intervention interval of 3 months. The primary outcome
      measures will include the incidence of prespecified administrationassociated adverse events
      (AEs) and serious adverse events (SAEs). The efficacy will be evaluated based on the absolute
      changes in the number of admissions, arterial blood gas analysis, lung function and lung
      fibrosis via CT scan and chest X-ray. The clinical evaluation will be conducted at baseline
      and 3, 6, and 12 months post
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Adverse events and serious adverse events
time frame: up to the 12-month period following treatment
description: To assess safety, the number of AEs or SAEs during stem cell administration (72 h) at 3 months, 6 months, and 12 months after discharge will be evaluated
measure: Quality of Life using Georges Respiratory Questionnaire
time frame: up to the 12-month period following treatment
description: Georges Respiratory Questionnaire has scores range from 0 to 100, with higher scores indicating more limitations
measure: Chest CT
time frame: up to the 12-month period following treatment
description: Changes of the lung fibrosis on chest CT at 6 months, and 12 months compared with baseline
measure: arterial blood gas analysis (pH)
time frame: up to the 12-month period following treatment
description: arterial blood gas analysis (pH)
measure: arterial blood gas analysis (PaO2)
time frame: up to the 12-month period following treatment
description: arterial blood gas analysis (PaO2)
measure: arterial blood gas analysis (PaCO2)
time frame: up to the 12-month period following treatment
description: arterial blood gas analysis (PaCO2)
measure: arterial blood gas analysis (BE)
time frame: up to the 12-month period following treatment
description: arterial blood gas analysis (BE)
measure: arterial blood gas analysis (HCO3-)
time frame: up to the 12-month period following treatment
description: arterial blood gas analysis (HCO3-)
measure: Respiratory functions (FEV1)
time frame: up to the 12-month period following treatment
description: Respiratory functions (FEV1)
measure: Respiratory functions (FEV1/FVC)
time frame: up to the 12-month period following treatment
description: Respiratory functions (FEV1/FVC)
measure: Respiratory functions (VC)
time frame: up to the 12-month period following treatment
description: Respiratory functions (VC)
measure: Respiratory functions (TLC)
time frame: up to the 12-month period following treatment
description: Respiratory functions (TLC)
measure: Respiratory functions (RV)
time frame: up to the 12-month period following treatment
description: Respiratory functions (RV)
measure: Respiratory functions (DLCO)
time frame: up to the 12-month period following treatment
description: Respiratory functions (DLCO)
measure: Respiratory functions (DLNO/DLCO)
time frame: up to the 12-month period following treatment
description: Respiratory functions (DLNO/DLCO)
measure: inflammatory response (CRP)
time frame: up to the 12-month period following treatment
description: inflammatory response (CRP)
measure: inflammatory response (Pro-BNP)
time frame: up to the 12-month period following treatment
description: inflammatory response (Pro-BNP)
measure: inflammatory response (Troponin-T)
time frame: up to the 12-month period following treatment
description: inflammatory response (Troponin-T)
measure: cytokine analysis from patients' plasma
time frame: up to the 12-month period following treatment
description: cytokine analysis from patients' plasma
measure: modified medical research council
time frame: up to the 12-month period following treatment
description: modified medical research council (mMRC)
arm group label: Treatment (UC-MSC trasnplatation)
arm group type: Experimental
description: 1 x 10^6 umbilical Cord Mesenchymal Stem Cells per body kg will transplant via the intravenous at baseline, and the second transplantation will be performed 3 months after the first transplantation and combination with Vietnames MOH procedure
arm group label: control arm
arm group type: Other
description: drug therapy according to Vietnamese MOHS procedure
intervention type: Biological
intervention name: Umbilical Cord Mesenchymal Stem Cells transplantation
description: Patients assigned to UC-MSC administration groups will receive two administrations at a dose of 1 million cells/kg patient body weight via the IV route with a 3-month intervening interval
arm group label: Treatment (UC-MSC trasnplatation)
intervention type: Drug
intervention name: drug therapy according to Vietnamese MOHS procedure
description: Salbutamol, Terbutaline
arm group label: Treatment (UC-MSC trasnplatation)
arm group label: control arm
criteria: 
gender: All
minimum age: 40 Years
maximum age: 75 Years
healthy volunteers: No
last name: Duc Minh Hoang, PhD
role: Principal Investigator
affiliation: Vinmec Research Institute of Stem Cell and Gene Technology
last name: Duc Minh Hoang, PhD
phone: (+84) 909 743 101
email: v.duchm3@vinmec.com
last name: Anh Hai Nguyen, MD., PhD
phone: (+84)968863668
email: haianhnguyenbm@gmail.com
facility: 
status: Recruiting
contact: 
country: Vietnam
citation: Ribeiro-Paes JT, Bilaqui A, Greco OT, Ruiz MA, Marcelino MY, Stessuk T, de Faria CA, Lago MR. Unicentric study of cell therapy in chronic obstructive pulmonary disease/pulmonary emphysema. Int J Chron Obstruct Pulmon Dis. 2011 Jan 1;6:63-71. doi: 10.2147/COPD.S15292.
PMID: 21311694
citation: Stessuk T, Ruiz MA, Greco OT, Bilaqui A, Ribeiro-Paes MJ, Ribeiro-Paes JT. Phase I clinical trial of cell therapy in patients with advanced chronic obstructive pulmonary disease: follow-up of up to 3 years. Rev Bras Hematol Hemoter. 2013;35(5):352-7. doi: 10.5581/1516-8484.20130113.
PMID: 24255620
citation: Stolk J, Broekman W, Mauad T, Zwaginga JJ, Roelofs H, Fibbe WE, Oostendorp J, Bajema I, Versteegh MI, Taube C, Hiemstra PS. A phase I study for intravenous autologous mesenchymal stromal cell administration to patients with severe emphysema. QJM. 2016 May;109(5):331-6. doi: 10.1093/qjmed/hcw001. Epub 2016 Jan 27.
PMID: 26819296
responsible party type: Sponsor
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
sharing ipd: No