A Pilot Study Evaluating Safety of Sitagliptin Combined With Peg-IFN Alfa-2a + Ribavirin in Chronic Hepatitis C Patients
Status:
Terminated
Trial end date:
2014-01-01
Target enrollment:
Participant gender:
Summary
Hepatitis C infection is a major public health problem with nearly 175 million infected
individuals worldwide. Although cure is possible, only 20-40% of patients spontaneously
resolve infection and 40-80% of chronically infected patients (numbers vary depending on
viral genotype) that receive pegylated-interferon-alfa2a/ribavirin therapy clear the virus
and are sustained virologic responders (SVR). Still for many, the virus manages to circumvent
natural immunity and current therapeutic strategies, resulting in significant morbidity and
mortality.
To better define the distinct clinical outcomes of HCV infection many investigators have
performed candidate molecules screens or transcriptional profiling in order to identify
correlates of viral clearance. One molecule that has gained significant attention is CXCL10
(also known as interferon-gamma induced protein-10 or IP-10) as an important negative
prognostic biomarker. Given that CXCL10 is produced by hepatocytes and mediates
chemo-attraction of activated lymphocytes expressing the CXCL10-receptor, CXCR3, it is
counter-intuitive as to why this chemokine correlates with therapeutic non-responsiveness.
The investigators hypothesized and have now demonstrated that CXCL10 is being cleaved in
situ, resulting in the generation of an antagonist form of the chemokine. Based on the use of
specific inhibitors, the investigators now propose to test whether protection of the agonist
form of CXCL10 will increase responsiveness to peg-IFN-alfa2 / ribavirin therapy. This can be
achieved using DPPIV inhibitors, targeting the enzyme responsible for N-terminal truncation
of CXCL10. If safety is confirmed, the efficacy of DPPIV-inhibition in HCV patients will be
tested in future trials that examine potential clearance benefits.