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The Relationship Between MDSCs and NK Cells Activity of CHC Patient Treated by DAAs

Primary Purpose

Chronic Hepatitis C

Status
Completed
Phase
Early Phase 1
Locations
Study Type
Interventional
Intervention
Ledipasvir-Sofosbuvir
Daclatasvir-Sofosbuvir
Sponsored by
Third Affiliated Hospital, Sun Yat-Sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Chronic Hepatitis C focused on measuring Chronic Hepatitis C, direct-acting antiviral agents, Myeloid-Derived Suppressor Cells, NK cells

Eligibility Criteria

18 Years - 76 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Positive serum Anti-HCV antibody or serum HCV-RNA, CHC patients without any treatment

Exclusion Criteria:

  • Patient has a history of clinical signs/symptoms of hepatic decompensation (Child-Pugh Grade B or C) or ascites, esophageal variceal bleeding, hepatic encephalopathy, or spontaneous bacterial peritonitis.
  • Patient has a history of hepatocellular carcinoma (HCC) or suspected symptoms of HCC, such as suspicious foci on imaging studies and/or serum alpha-fetoprotein (AFP)>50ng/mL.
  • Patient has received IFN or other immunomodulatory treatment within 52 weeks before Screening.

Patient has a medical condition that requires frequent use of systemic acyclovir or famciclovir.

  • Patient has a medical condition that requires frequent use of systemic corticosteroids, however topical and inhaled corticosteroids are allowed.

Patient has used hepatotoxic drugs within one month. Patient has overtaken alcohol (>40g/day) or abused illicit drugs in recent one year.

  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive urine pregnancy test.
  • Patients who co-infected with HAV, HBV, HDV, HEV,HIV(human immunodeficiency virus ) Patient has one or more additional known primary or secondary causes of liver disease, other than hepatitis C (e.g., alcoholism, autoimmune hepatitis).

History of malignancy of any organ system.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    No Intervention

    Arm Label

    CHC patients

    Healthy controls

    Arm Description

    32 treatment-naive CHC patients treated by Ledipasvir-Sofosbuvir or Daclatasvir-Sofosbuvir.

    20 Healthy controls without any treatment

    Outcomes

    Primary Outcome Measures

    Changes of the frequency of CD14+CD11b+CD33+HLA-DR-/low MDSCs
    Measurement of the frequency of CD14+CD11b+CD33+HLA-DR-/low MDSCs of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks (24 weeks after DAAs treatment)

    Secondary Outcome Measures

    Changes of the frequency of CD14+HLA-DR-/low M-MDSCs
    Measurement of the frequency of CD14+HLA-DR-/low M-MDSCs of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks (24 weeks after DAAs treatment)
    Changes of the frequency of CD3+CD4+ T cells
    Measurement of the frequency of CD3+CD4+ T cells of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks (24 weeks after DAAs treatment)
    Changes of the frequency of CD3+CD8+ T cells
    Measurement of the frequency of CD3+CD8+ T cells of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks (24 weeks after DAAs treatment)
    Changes of the frequency of CD3CD56+ NK cells
    Measurement of the frequency of CD3CD56+ NK cells of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks (24 weeks after DAAs treatment)
    Changes of the frequency of NKG2A in CD3CD56+ NK cells
    Measurement of the frequency of NKG2A in CD3CD56+ NK cells of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks (24 weeks after DAAs treatment)
    Changes of the frequency of NKp30 in CD3CD56+ NK cells
    Measurement of the frequency of NKp30 in CD3CD56+ NK cells of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks (24 weeks after DAAs treatment)
    Changes of the frequency of NKp46 in CD3CD56+ NK cells
    Measurement of the frequency of NKp46 in CD3CD56+ NK cells of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks (24 weeks after DAAs treatment)

    Full Information

    First Posted
    June 11, 2017
    Last Updated
    June 14, 2017
    Sponsor
    Third Affiliated Hospital, Sun Yat-Sen University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03188276
    Brief Title
    The Relationship Between MDSCs and NK Cells Activity of CHC Patient Treated by DAAs
    Official Title
    The Relationship Between Direct Acting Antiviral Treatment Effect and Myeloid-Derived Suppressor Cells and NK Cells Activity in Chronic Hepatitis C
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2017
    Overall Recruitment Status
    Completed
    Study Start Date
    February 1, 2016 (Actual)
    Primary Completion Date
    May 1, 2017 (Actual)
    Study Completion Date
    May 1, 2017 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Third Affiliated Hospital, Sun Yat-Sen University

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    Hepatitis C virus (HCV) infection is easy to chronic and can progress to cirrhosis and liver cancer. Direct-acting antiviral treatment can significantly improve the prognosis of the disease and the efficacy is seemingly not affected by a variety of viral factors. In addition, direct-acting antiviral agents therapy may affect the transformation of the immune cells and ameliorate the host immune status consequently. This study mainly investigated the relationship between Direct Acting Antiviral Treatment effect and the functional activity of myeloid-derived suppressor cells (MDSCs) and natural killer cells (NK cells) in Chronic Hepatitis C.
    Detailed Description
    32 treatment-naive CHC patients and 20 healthy controls were recruited. Patients were examined before DAAs therapy (0w) and at weeks 4 (4w) and weeks 12 (12w) and weeks24 (24w) of the therapy. The percent age of myeloid-derived suppressor cells and NK cells of the peripheral blood were analyzed by flow cytometry. The investigators discuss the relationship between direct acting antiviral treatment effect and myeloid-derived suppressor cells and NK cells activity in chronic hepatitis C.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Chronic Hepatitis C
    Keywords
    Chronic Hepatitis C, direct-acting antiviral agents, Myeloid-Derived Suppressor Cells, NK cells

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Early Phase 1
    Interventional Study Model
    Single Group Assignment
    Model Description
    There are 32 treatment-naive CHC patients who treated by Ledipasvir-Sofosbuvir or Daclatasvir-Sofosbuvir.
    Masking
    None (Open Label)
    Masking Description
    Thr care provider, participant, investigator and outcomes assessor all konw the process.
    Allocation
    Non-Randomized
    Enrollment
    52 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    CHC patients
    Arm Type
    Active Comparator
    Arm Description
    32 treatment-naive CHC patients treated by Ledipasvir-Sofosbuvir or Daclatasvir-Sofosbuvir.
    Arm Title
    Healthy controls
    Arm Type
    No Intervention
    Arm Description
    20 Healthy controls without any treatment
    Intervention Type
    Drug
    Intervention Name(s)
    Ledipasvir-Sofosbuvir
    Other Intervention Name(s)
    Harvoni
    Intervention Description
    15 CHC patients were treated with Sofosbuvir (400mg, qd)/Ledipasvir (90mg, qd) for 12 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    Daclatasvir-Sofosbuvir
    Other Intervention Name(s)
    Daklinza
    Intervention Description
    17 CHC patients were treated with Sofosbuvir (400mg, qd)/Daclatasvir (60mg,qd) for 12 weeks.
    Primary Outcome Measure Information:
    Title
    Changes of the frequency of CD14+CD11b+CD33+HLA-DR-/low MDSCs
    Description
    Measurement of the frequency of CD14+CD11b+CD33+HLA-DR-/low MDSCs of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks (24 weeks after DAAs treatment)
    Time Frame
    0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks ( 24 weeks after DAAs treatment)
    Secondary Outcome Measure Information:
    Title
    Changes of the frequency of CD14+HLA-DR-/low M-MDSCs
    Description
    Measurement of the frequency of CD14+HLA-DR-/low M-MDSCs of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks (24 weeks after DAAs treatment)
    Time Frame
    0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks ( 24 weeks after DAAs treatment)
    Title
    Changes of the frequency of CD3+CD4+ T cells
    Description
    Measurement of the frequency of CD3+CD4+ T cells of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks (24 weeks after DAAs treatment)
    Time Frame
    0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks ( 24 weeks after DAAs treatment)
    Title
    Changes of the frequency of CD3+CD8+ T cells
    Description
    Measurement of the frequency of CD3+CD8+ T cells of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks (24 weeks after DAAs treatment)
    Time Frame
    0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks ( 24 weeks after DAAs treatment)
    Title
    Changes of the frequency of CD3CD56+ NK cells
    Description
    Measurement of the frequency of CD3CD56+ NK cells of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks (24 weeks after DAAs treatment)
    Time Frame
    0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks ( 24 weeks after DAAs treatment)
    Title
    Changes of the frequency of NKG2A in CD3CD56+ NK cells
    Description
    Measurement of the frequency of NKG2A in CD3CD56+ NK cells of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks (24 weeks after DAAs treatment)
    Time Frame
    0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks ( 24 weeks after DAAs treatment)
    Title
    Changes of the frequency of NKp30 in CD3CD56+ NK cells
    Description
    Measurement of the frequency of NKp30 in CD3CD56+ NK cells of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks (24 weeks after DAAs treatment)
    Time Frame
    0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks ( 24 weeks after DAAs treatment)
    Title
    Changes of the frequency of NKp46 in CD3CD56+ NK cells
    Description
    Measurement of the frequency of NKp46 in CD3CD56+ NK cells of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks (24 weeks after DAAs treatment)
    Time Frame
    0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks ( 24 weeks after DAAs treatment)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    76 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: Positive serum Anti-HCV antibody or serum HCV-RNA, CHC patients without any treatment Exclusion Criteria: Patient has a history of clinical signs/symptoms of hepatic decompensation (Child-Pugh Grade B or C) or ascites, esophageal variceal bleeding, hepatic encephalopathy, or spontaneous bacterial peritonitis. Patient has a history of hepatocellular carcinoma (HCC) or suspected symptoms of HCC, such as suspicious foci on imaging studies and/or serum alpha-fetoprotein (AFP)>50ng/mL. Patient has received IFN or other immunomodulatory treatment within 52 weeks before Screening. Patient has a medical condition that requires frequent use of systemic acyclovir or famciclovir. Patient has a medical condition that requires frequent use of systemic corticosteroids, however topical and inhaled corticosteroids are allowed. Patient has used hepatotoxic drugs within one month. Patient has overtaken alcohol (>40g/day) or abused illicit drugs in recent one year. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive urine pregnancy test. Patients who co-infected with HAV, HBV, HDV, HEV,HIV(human immunodeficiency virus ) Patient has one or more additional known primary or secondary causes of liver disease, other than hepatitis C (e.g., alcoholism, autoimmune hepatitis). History of malignancy of any organ system.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Zhi-liang Gao, PhD
    Organizational Affiliation
    Third Affiliated Hospital, Sun Yat-Sen University
    Official's Role
    Study Chair

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    IPD Sharing Plan Description
    Individual participant data (IPD) is not available to other researchers

    Learn more about this trial

    The Relationship Between MDSCs and NK Cells Activity of CHC Patient Treated by DAAs

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