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

NCT03188276 | Completed Early Phase 1 DMC

• 1 other identifier: Effect of DAAs on MDSCs and NK
• Study Type: interventional
• Target: 52
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Chronic Hepatitis C

Keywords

Chronic Hepatitis C; direct-acting antiviral agents; Myeloid-Derived Suppressor Cells; NK cells

Outcome Measures

Primary Outcomes (1)

• 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)

  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 Outcomes (7)

• Changes of the frequency of CD14+HLA-DR-/low M-MDSCs

  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

  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

  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

  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

  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)

Study Arms (2)

CHC patients

ACTIVE COMPARATOR

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

Drug: Ledipasvir-Sofosbuvir; Drug: Daclatasvir-Sofosbuvir

Healthy controls

NO INTERVENTION

20 Healthy controls without any treatment

Interventions

Ledipasvir-Sofosbuvir DRUG

15 CHC patients were treated with Sofosbuvir (400mg, qd)/Ledipasvir (90mg, qd) for 12 weeks

Also known as: Harvoni

CHC patients

Daclatasvir-Sofosbuvir DRUG

17 CHC patients were treated with Sofosbuvir (400mg, qd)/Daclatasvir (60mg,qd) for 12 weeks.

Also known as: Daklinza

CHC patients

Eligibility Criteria

• Age: 18 Years - 76 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Third Affiliated Hospital, Sun Yat-Sen University: lead

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

ledipasvir, sofosbuvir drug combination; daclatasvir

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Zhi-liang Gao, PhD

  Third Affiliated Hospital, Sun Yat-Sen University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Thr care provider, participant, investigator and outcomes assessor all konw the process.
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: There are 32 treatment-naive CHC patients who treated by Ledipasvir-Sofosbuvir or Daclatasvir-Sofosbuvir.

Study Record Dates

• First Submitted: June 11, 2017
• First Posted: June 15, 2017
• Study Start: February 1, 2016
• Primary Completion: May 1, 2017
• Study Completion: May 1, 2017
• Last Updated: June 15, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share