Differences in Evoked Intracellular Interferon Signaling Pathways Using Single Cell Phosphoprotein Profiling

Purpose:

The purpose of this exploratory study is to evaluate phosphoprotein profiling to determine differences in the intracellular actions of interferon or interferon stimulated genes among people with different treatment outcomes to interferon based therapy for hepatitis C (HCV). Participants: Patients with genotype 1 HCV who have had interferon based therapy at the University of North Carolina (UNC). Procedures: Thirty patients with varied responses to treatment will be given a single subcutaneous injection of interferon alpha 2b. Prior to the injection and at 30 minutes, 1,2,4,6,12 and 20 hours after injection, blood will be drawn for analysis of phosphoprotein profiling and changes in serum cytokines.

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: Interferon Alfa-2b

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

To be eligible for this study, subjects must meet the following inclusion criteria:

• Willing and able to provide informed consent
• Males or females age 18 - 65 years
• For women of childbearing potential, negative blood pregnancy test documented within the 24-hour period prior to IFN-α administration
• History of genotype 1 HCV infection previously treated with peginterferon and ribavirin and with a virological response that can be determined from retrospective review of medical records
• A washout period of >12 weeks between the last dose of prescribed peginterferon and ribavirin and the screening visit

Exclusion Criteria

Subjects with any of the following will not be eligible for participation:

• Neutrophil count <1500 cells/mm3, Hgb <12 g/dL in women or 13 g/dL in men, or platelet count <75,000 cells/mm3 at screening
• Serum creatinine level >1.5 times the upper limit of normal at screening
• Poorly controlled psychiatric illness, as determined by the study physician, which can be exacerbated by interferon therapy
• Infection requiring antibiotics, symptomatic viral infection, inflammatory process requiring therapy, or allergic reactions in the week immediately preceding the inpatient study visit
• Use of medications that affect the immune system (e.g. glucocorticoids, chronic NSAIDs daily) in the week immediately preceding the inpatient study visit
• History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, psoriasis, rheumatoid arthritis)
• Women with ongoing pregnancy or breast-feeding
• History or other evidence of bleeding from esophageal varices or other conditions consistent with decompensated liver disease
• History of a seizure disorder or current anticonvulsant use
• History of major organ transplantation with an existing functional graft
• History of thyroid disease poorly controlled on prescribed medications
• History or other evidence of severe illness or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Interferon Alfa-2b; Patients will receive a single dose of interferon	Drug: Interferon Alfa-2b; Patients will receive a single dose of interferon followed by serial blood draws to assess cellular responses to interferon; Other Names: Intron A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Protein quantification of interferon stimulated genes (ISG)	This is an exploratory study observing downstream phosphorylation of interferon stimulated genes in the Janus Activated Kinase (JAK-STAT) pathway.	0-20 hours

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: Tibotec Pharmaceutical Limited
• Investigators: Principal Investigator: Sid Barritt, MD, MSCR, University of North Carolina, Chapel Hill

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: September 30, 2010
• First Submitted That Met QC Criteria: October 6, 2010
• First Posted (Estimate): October 8, 2010

Study Record Updates

• Last Update Posted (Estimate): November 15, 2016
• Last Update Submitted That Met QC Criteria: November 11, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Hepatitis C; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Immunologic Factors; Interferons; Interferon-alpha; Interferon alpha-2
• Other Study ID Numbers: 08-2040

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO