Clinical trial NCT02532907: Study of Hepatic Responses in Patients Receiving Direct-acting Anti-HCV Drugs
Official title: Study of Hepatic Responses in Patients Receiving Direct-acting Anti-HCV Drugs
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hepatitis C
Keywords: HCV
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2015-08-26
Enrollment: 5
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: PROBABILITY_SAMPLE
Study population: Recruitment of patients will primarily occur through the Hepatology clinic, so non-veterans will be recruited. A total of 20 HCV-positive patients who will be treated with FDA-approved treatments as covered by the patient's insurance. Half of the patients will be treatment-naïve prior to enrollment and half will be treatment-experienced with either null response or relapse, i.e., persistent viremia. An equal proportion in each group will be biopsied at 4 versus 12 weeks after first dosing of DAA. Patients will be subjected to two biopsies during the life of the study.

Brief summary: This study is designed to obtain and store samples of serum and liver tissue in HCV (HepC Virus)-infected patients being treated with direct-acting antiviral (DAA) therapy, and to determine the effect of new DAA therapies on HCV-related responses in the liver and peripheral blood.

The introduction of new DAAs regimens that do not include IFN provides unique and novel opportunities to examine whether successful treatment-induced eradication of viral antigen results in reconstitution of T cell immunity. serum and liver tissue samples will be collected and stored in hopes of improving treatment and outcomes for future patients.

Detailed description: This study is designed to obtain and store samples of serum and liver tissue in HCV-infected patients being treated with DAA therapy.

A liver biopsy will be performed pre-treatment for research reasons. A small liver sample that is not required for pathologic analysis will also be stored. Patients will undergo another liver biopsy at either 4 or 12 weeks after initiation of DAA therapy.

Any patients with HCV-related liver disease (age \> 18) will be considered for this study.

Patients will have a 120 ml blood draw for research purposes at baseline and 12 weeks after stopping DAA treatment along with a 60 ml blood draw at 2, 4, 8, and 12 weeks of treatment.

The liver biopsy at baseline and then either at 4 or 12 weeks will be examined using molecular techniques to measure transcription of key genes involved in the antiviral response.

Eligibility criteria: Inclusion Criteria

* Signed informed consent
* Ages 18-70
* HCV-infected patients being treated with direct-acting antiviral (DAA) therapy.

Exclusion Criteria

* Pregnant women or females of childbearing potential that are not on contraception
* Institutionalized or mentally disabled persons
* Prisoners
* Unwilling or unable to provide informed consent
* Subjects who are HIV positive
* Anticipated inability to follow up
* Chronic anemia
* Platelet count \< 100 for liver biopsy patients who have documented fatty liver disease by ultrasound prior to enrollment
* Any patient with bleeding disorders or prolonged INR
* Abstinent or consuming less than two drinks of alcohol per day.
* Clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage).

Primary outcomes:
measure: Changes in gene array from baseline to either 4 or 12 weeks after treatment.
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Sandra Boimbo
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Hugo Rosen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Golden-Mason L, Palmer B, Klarquist J, Mengshol JA, Castelblanco N, Rosen HR. Upregulation of PD-1 expression on circulating and intrahepatic hepatitis C virus-specific CD8+ T cells associated with reversible immune dysfunction. J Virol. 2007 Sep;81(17):9249-58. doi: 10.1128/JVI.00409-07. Epub 2007 Jun 13.