Clinical trial NCT00422838: Study Investigating Immunological Effects of Treatment for Chronic Hepatitis C Patients.
Official title: Impact of Immune Responses in Chronic Hepatitis C Genotype 1,2,3 Virus Infected Patients During Treatment With Pegylated Interferon-alpha-2b and Ribavirin (CIRES).
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hepatitis C
Liver
Immunology
Regulation
Keywords: Hepatitis C
Liver
immunology
regulation
Genotype 1,2,3
Treatment
Chronic
Pegylated interferon
Ribavirin
Lead sponsor: Foundation for Liver Research
Sponsor class: OTHER
First posted: 2007-01-17
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients chronically infected with HCV-genotype 1,2 or 3

Brief summary: Aim

To evaluate the effects of peginterferon and ribavirin therapy on the immune response in chronic HCV genotype 1,2 or 3 patients before, during and after treatment.

Background

Treatment of chronic hepatitis C (HCV) has shown a remarkable success. However, genotype 1 patients have reduced response rates. A better understanding and improvement of these results can now be considered the greatest challenge.

In chronically infected patients, HCV-specific immune responses are generally weak, narrowly focused, and often dysfunctional. The presence of HCV-specific cells suppressing the immune response (regulatory T-lymphocytes=Treg) are able to suppress the immune response. These Treg are possibly responsible for the impaired immune response.

Previous studies have indicated increased Treg frequency and activity of immune regulating mechanisms, locally in the liver, as a result of HCV re-infection. Hence, these Data highlight the importance of monitoring intrahepatic immune responses in addition to peripheral immune responses. Using the minimally-invasive technique of fine-needle aspiration biopsy (FNAB), it is now possible to obtain safe and frequent liver samples to monitor local antiviral immune responses in chronic HCV patients during antiviral therapy.

Rationale and hypothesis of the study

Our previous studies and current literature support the concept that Treg may contribute to HCV persistence by suppressing HCV-spec immune responses. The current study is designed to examine if peginterferon and ribavirin therapy affects the activity of Treg and DC, and if this results in enhanced HCV-specific immune responses.

Design

Single centre, translational and observational open label study with one arm of 20 genotype 1 patients and one arm of 7 genotype 2/3 patients.


Eligibility criteria: Inclusion Criteria:

* Male and female patients between 18-70 years of age, with evidence of a chronic hepatitis C - Genotype 1,2 or 3 infection.
* No previous treatment with, peginterferon or conventional interferon plus ribavirin combination therapy.
* Indication for antiviral therapy of hepatitis C according to current clinical guidelines.
* Written informed consent.

Exclusion Criteria:

* History or other evidence of severe illness, malignancy or any other condition which would make the patient, in the opinion of the investigators, unsuitable for the study.
* Presence of contra-indications for antiviral therapy with peginterferon or ribavirin.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Rotterdam
country: Netherlands
facility: Department of Gastroenterology & Hepatology, Erasmus Medical Center
state: Zuid-Holland
Study officials:
affiliation: Department of Gastroenterology & Hepatology - Erasmus Medical Center Rotterdam
name: R.J. de Knegt, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Gastroenterology & Hepatology - Erasmus Medical Center Rotterdam
name: H.L.A. Janssen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: