Impact of Interferon-free Treatment for Hepatitis C Virus (HCV) on Blood Cells and Factors in Blood

Hepatitis C Clinical Trial

Official title:

Impact of Interferon-free Treatment for Hepatitis C Virus (HCV) on Blood Cells and Factors in Blood

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02718573
• Other study ID #: GCO 14-2222
• Status: Completed
• Phase: N/A
• First received: March 18, 2016
• Last updated: January 16, 2018
• Start date: January 2015
• Est. completion date: December 11, 2017

Study information

• Verified date: January 2018
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The objectives of the study are to determine the impact of interferon-free treatment for the hepatitis C virus (HCV) on peripheral blood immune cell phenotype and soluble immune-related proteins in blood, while controlling for genetic polymorphisms known to impact HCV-related immune responses, and to determine the impact of the therapy on the emergence of drug-resistant HCV. The study design is informed by the researchers recent investigations of patients receiving HCV treatment. About 4% of patients who had not undergone liver transplantation experienced hepatic decompensating or another serious event. There were several cases of bacterial infection and two cases with elevated markers of autoimmune processes. These events suggest that treatment altered immune responses. About 25% of patients who had undergone liver transplantation experienced hepatic decompensating or another serious adverse event. The long term goal is to understand the pathophysiology of these complications and determine whether HCV treatment can cause an immune reconstitution syndrome in susceptible patients, while improving antimicrobial defenses in others

Description:

The objectives of the study are to determine the impact of interferon-free treatment for the hepatitis C virus (HCV) on peripheral blood immune cell phenotype and soluble immune-related proteins in blood, while controlling for genetic polymorphisms known to impact HCV-related immune responses, and to determine the impact of the therapy on the emergence of drug-resistant HCV. The study design is informed by the researchers' recent investigations of patients receiving HCV treatment. About 4% of patients who had not undergone liver transplantation experienced hepatic decompensation or another serious event. There were several cases of bacterial infection and two cases with elevated markers of autoimmune processes. These events suggest that treatment altered immune responses. About 25% of patients who had undergone liver transplantation experienced hepatic decompensation or another serious adverse event. The long term goal is to understand the pathophysiology of these complications and determine whether HCV treatment can cause an immune reconstitution syndrome in susceptible patients, while improving antimicrobial defenses in others The main questions/objectives to be addressed are (1) to determine the effect of HCV treatment on the profile of immune cells in blood as assessed by cytometry time of flight (CyTOF) multiparameter analysis, while controlling for genetic polymorphisms known to be associated with HCV-related immune responses and, (2) to determine the effect of treatment on factors/proteins in blood that may be related to immunity and inflammation.

Background: New treatments for HCV are significantly more effective than past treatments. They utilize direct acting antiviral drugs (DAA) and many do not include interferon. The goal of treatment is to achieve a sustained virological response (SVR). An SVR is indicated by the absence of detectable HCV RNA in blood 12 weeks after the end of treatment (EOT); this is called SVR12. The researchers recently investigated outcomes of 514 non-liver transplant (LT) patients and 43 LT patients who initiated treatment between Dec 2013 and June 2014. Several patients developed increased levels of markers of autoimmune processes and/or experienced a bacterial infection. Investigators at other institutions recently reported evidence that DAA treatment enhances immune cell activation. The combination of the investigators' observations and the observations of others indicates that a detailed investigation is needed to understand the events leading to increased immune cell activity and to determine the factors that may increase the risk of serious adverse events.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: December 11, 2017
• Est. primary completion date: December 11, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion for non-LT patients:

• Adult

• Not pregnant

• Positive test for HCV RNA and planning to start interferon-free treatment soon

• Not HIV infected

• Able and willing to travel to Mount Sinai at the time points need for blood draws--prior to the start of treatment (within one month of the actual start date), at the 4th week of treatments (plus or minus two weeks), at the 12th week of treatment (plus or minus two weeks).

• Must understand and speak English

• Medically stable

• Willing to sign informed consent and participate

Inclusion criteria for LT patients:

• All of the above

• At least 6 months post-LT

• On stable immunosuppressive medications for at least 3 months LT only (no other organ transplant, such as kidney)

Related Conditions & MeSH terms

• HCV
• Hepatitis
• Hepatitis A
• Hepatitis C
• Liver Transplant

Locations

Country	Name	City	State
United States	Icahn School of Medicine at Mount Sinai	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	cytometry time of flight (CyTOF)	the profile of immune cells in blood as assessed by cytometry time of flight (CyTOF) multiparameter analysis	up to week 14
Secondary	CD8 T cells	Change in the percentage of CD8 Tcells level	Baseline and week 14
Secondary	HCV resistance mutations	Incidence of emergence of HCV resistance mutations	up to week 14