<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/NCT04470323</url>
  </required_header>
  <id_info>
    <org_study_id>T cells</org_study_id>
    <nct_id>NCT04470323</nct_id>
  </id_info>
  <brief_title>Functional Exhaustion of T Cells in COVID19 Patients</brief_title>
  <official_title>Functional Exhaustion of T Cells in COVID19 Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assiut University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assiut University</source>
  <oversight_info>
    <has_dmc>No</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>
      The primary end-point of our prospective, observational study is to count T cells in patients&#xD;
      with laboratory-confirmed COVID-19 and healthy controls. In addition, the expression of T&#xD;
      cell exhaustion marker was measured in COVID-19 cases.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed&#xD;
      great threat to human health. T cells play a critical role in antiviral immunity but their&#xD;
      numbers and functional state in COVID-19 patients remain largely unclear. The immune response&#xD;
      against viral infections depends on the activation of cytotoxic T cells that can clear&#xD;
      infection by killing virus-infected cells, so boosting the numbers and function of T cells in&#xD;
      COVID-19 patients is critical for successful recovery. However, the factors which might cause&#xD;
      the reduction in count, and the activation status of T cells in COVID-19 patients, remain&#xD;
      uninvestigated. Thus demonstration of T cell exhaustion during COVID-19 infection suggest&#xD;
      that more urgent, early intervention may be required in patients with low T lymphocyte&#xD;
      counts.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">July 22, 2020</start_date>
  <completion_date type="Anticipated">November 2020</completion_date>
  <primary_completion_date type="Anticipated">October 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>CD4+ (T-helper cells) in COVID 19 patients and healthy volunteers.</measure>
    <time_frame>Baseline</time_frame>
    <description>Detection of the percentage of CD4+ (T-helper cells) in COVID 19 patients and healthy volunteers.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>CD8+ (T-cytotoxic cells) in COVID 19 patients and healthy volunteers.</measure>
    <time_frame>Baseline</time_frame>
    <description>Detection of the percentage of CD8+ (T-cytotoxic cells) in COVID 19 patients and healthy volunteers .</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Detect PD-1 on CD8+ and CD4+ cells in COVID 19 patients and healthy volunteers .</measure>
    <time_frame>Baseline</time_frame>
    <description>Detection of the percentage of expression of PD-1 on CD8+ and CD4+ cells in COVID 19 patient and healthy volunteers.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Detect CD28+ and CD3+ cells in COVID 19 patients and healthy volunteers.</measure>
    <time_frame>Baseline</time_frame>
    <description>Detection of the frequency of CD28+ and CD3+ cells in COVID 19 patients and healthy volunteers .</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">100</enrollment>
  <condition>T Cell Deficiency</condition>
  <arm_group>
    <arm_group_label>COVID19 patients</arm_group_label>
    <description>Patients admitted to Assiut university Hospitals diagnosed as COVID19 positive patients by PCR.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>healthy volunteer</arm_group_label>
    <description>as negative control for each sample</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Flow cytometry</intervention_name>
    <description>Lymphocyte subsets in peripheral blood were assessed by staining 50 µl of blood sample with 5 µl of Fluoroisothiocyanate (FITC)-conjugated- PD-1, phycoerythrin (PE)-conjugated-CD8, peridinium-chlorophyll-protein (Per-CP)-conjugated-CD4, Peridinium-chlorophyll-protein (Per-CP)-conjugated anti-CD3 and allophycocyanin (APC) conjugated anti-CD28.</description>
    <arm_group_label>COVID19 patients</arm_group_label>
    <arm_group_label>healthy volunteer</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Peripheral blood samples from patients and healthy volunteers were supplemented with&#xD;
      anticoagulants (EDTA-K2).&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients admitted to Assiut university Hospitals diagnosed as COVID-19 positive patients by&#xD;
        PCR.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of Covid-19 test positive; hospitalized subjects; both sexes; given informed&#xD;
             consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  no exclusion criteriae&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Hebatallah Hassan, Lecturer</last_name>
    <phone>01022182086</phone>
    <email>heba.ismailhassan@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Faculty of Medicine</name>
      <address>
        <city>Assiut</city>
        <zip>71515</zip>
        <country>Egypt</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <reference>
    <citation>Diao B, Wang C, Tan Y, Chen X, Liu Y, Ning L, Chen L, Li M, Liu Y, Wang G, Yuan Z, Feng Z, Zhang Y, Wu Y, Chen Y. Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19). Front Immunol. 2020 May 1;11:827. doi: 10.3389/fimmu.2020.00827. eCollection 2020.</citation>
    <PMID>32425950</PMID>
  </reference>
  <reference>
    <citation>Li CK, Wu H, Yan H, Ma S, Wang L, Zhang M, Tang X, Temperton NJ, Weiss RA, Brenchley JM, Douek DC, Mongkolsapaya J, Tran BH, Lin CL, Screaton GR, Hou JL, McMichael AJ, Xu XN. T cell responses to whole SARS coronavirus in humans. J Immunol. 2008 Oct 15;181(8):5490-500. doi: 10.4049/jimmunol.181.8.5490.</citation>
    <PMID>18832706</PMID>
  </reference>
  <reference>
    <citation>Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24. Erratum In: Lancet. 2020 Jan 30;:</citation>
    <PMID>31986264</PMID>
  </reference>
  <reference>
    <citation>Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Feb 15;395(10223):507-513. doi: 10.1016/S0140-6736(20)30211-7. Epub 2020 Jan 30.</citation>
    <PMID>32007143</PMID>
  </reference>
  <reference>
    <citation>Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Mar 17;323(11):1061-1069. doi: 10.1001/jama.2020.1585. Erratum In: JAMA. 2021 Mar 16;325(11):1113.</citation>
    <PMID>32031570</PMID>
  </reference>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>July 12, 2020</study_first_submitted>
  <study_first_submitted_qc>July 12, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 14, 2020</study_first_posted>
  <last_update_submitted>August 4, 2020</last_update_submitted>
  <last_update_submitted_qc>August 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 6, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Assiut University</investigator_affiliation>
    <investigator_full_name>Hebatallah Hassan</investigator_full_name>
    <investigator_title>dr</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/NCT04470323
org study id: T cells
nct id: NCT04470323
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The primary end-point of our prospective, observational study is to count T cells in patients
      with laboratory-confirmed COVID-19 and healthy controls. In addition, the expression of T
      cell exhaustion marker was measured in COVID-19 cases.
COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed
      great threat to human health. T cells play a critical role in antiviral immunity but their
      numbers and functional state in COVID-19 patients remain largely unclear. The immune response
      against viral infections depends on the activation of cytotoxic T cells that can clear
      infection by killing virus-infected cells, so boosting the numbers and function of T cells in
      COVID-19 patients is critical for successful recovery. However, the factors which might cause
      the reduction in count, and the activation status of T cells in COVID-19 patients, remain
      uninvestigated. Thus demonstration of T cell exhaustion during COVID-19 infection suggest
      that more urgent, early intervention may be required in patients with low T lymphocyte
      counts.
observational model: Case-Control
time perspective: Prospective
measure: CD4+ (T-helper cells) in COVID 19 patients and healthy volunteers.
time frame: Baseline
description: Detection of the percentage of CD4+ (T-helper cells) in COVID 19 patients and healthy volunteers.
measure: CD8+ (T-cytotoxic cells) in COVID 19 patients and healthy volunteers.
time frame: Baseline
description: Detection of the percentage of CD8+ (T-cytotoxic cells) in COVID 19 patients and healthy volunteers .
measure: Detect PD-1 on CD8+ and CD4+ cells in COVID 19 patients and healthy volunteers .
time frame: Baseline
description: Detection of the percentage of expression of PD-1 on CD8+ and CD4+ cells in COVID 19 patient and healthy volunteers.
measure: Detect CD28+ and CD3+ cells in COVID 19 patients and healthy volunteers.
time frame: Baseline
description: Detection of the frequency of CD28+ and CD3+ cells in COVID 19 patients and healthy volunteers .
arm group label: COVID19 patients
description: Patients admitted to Assiut university Hospitals diagnosed as COVID19 positive patients by PCR.
arm group label: healthy volunteer
description: as negative control for each sample
intervention type: Diagnostic Test
intervention name: Flow cytometry
description: Lymphocyte subsets in peripheral blood were assessed by staining 50 µl of blood sample with 5 µl of Fluoroisothiocyanate (FITC)-conjugated- PD-1, phycoerythrin (PE)-conjugated-CD8, peridinium-chlorophyll-protein (Per-CP)-conjugated-CD4, Peridinium-chlorophyll-protein (Per-CP)-conjugated anti-CD3 and allophycocyanin (APC) conjugated anti-CD28.
arm group label: COVID19 patients
arm group label: healthy volunteer
Peripheral blood samples from patients and healthy volunteers were supplemented with
      anticoagulants (EDTA-K2).
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Hebatallah Hassan, Lecturer
phone: 01022182086
email: heba.ismailhassan@gmail.com
facility: 
status: Recruiting
country: Egypt
citation: Diao B, Wang C, Tan Y, Chen X, Liu Y, Ning L, Chen L, Li M, Liu Y, Wang G, Yuan Z, Feng Z, Zhang Y, Wu Y, Chen Y. Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19). Front Immunol. 2020 May 1;11:827. doi: 10.3389/fimmu.2020.00827. eCollection 2020.
PMID: 32425950
citation: Li CK, Wu H, Yan H, Ma S, Wang L, Zhang M, Tang X, Temperton NJ, Weiss RA, Brenchley JM, Douek DC, Mongkolsapaya J, Tran BH, Lin CL, Screaton GR, Hou JL, McMichael AJ, Xu XN. T cell responses to whole SARS coronavirus in humans. J Immunol. 2008 Oct 15;181(8):5490-500. doi: 10.4049/jimmunol.181.8.5490.
PMID: 18832706
citation: Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24. Erratum In: Lancet. 2020 Jan 30;:
PMID: 31986264
citation: Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Feb 15;395(10223):507-513. doi: 10.1016/S0140-6736(20)30211-7. Epub 2020 Jan 30.
PMID: 32007143
citation: Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Mar 17;323(11):1061-1069. doi: 10.1001/jama.2020.1585. Erratum In: JAMA. 2021 Mar 16;325(11):1113.
PMID: 32031570
responsible party type: Principal Investigator
investigator affiliation: Assiut University
investigator full name: Hebatallah Hassan
investigator title: dr
sharing ipd: No