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
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
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
NCT ID
NCT03188276
First Posted
June 11, 2017
Last Updated
June 14, 2017
Sponsor
Third Affiliated Hospital, Sun Yat-Sen University
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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