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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-000823-34 | EudraCT Number |
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New treatments available, which prevents additional recruitment.
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| DPPIV Inhibition | Experimental | The study includes an initial phase of 3 weeks with administration of sitagliptin (100 mg/d) as monotherapy, followed immediately by 12 weeks of triple therapy (sitagliptin 100 mg/d combined with peg-IFN alfa-2a and ribavirin). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sitagliptin | Drug | 100 mg Sitagliptin daily for 15 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety (Number of adverse events, Toxicity grade > 3) | After Day 1 until the end of the trial, i.e. a duration of 15 weeks for each patient |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Viral Load as compared to baseline | week 1, 2, 3 of sitagliptin monotherapy; week 2, 4, 12 of triple therapy | |
| Metabolic studies: Oral glucose tolerance will be assessed | baseline, week 1 of sitagliptin monotherapy; week 2 of triple therapy |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Matthew L. ALBERT, MD, PhD | Institut National de la Santé Et de la Recherche Médicale, France | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre Hospitalier Victor Dupuy | Argenteuil | 95100 | France | |||
| Centre Hospitalier Intercommunal Créteil |
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| Immunologic study | Monitoring the short and long form of IP-10 as compared to the total plasma concentration (three distinct ELISA assays). | baseline, week 1 and 3 of sitagliptin monotherapy; week 1, 2, 4, 12 of triple therapy |
| Immunologic study | Plasma concentration and activity of DPPIV (measured using an ELISA and a luciferase-based bioassay, respectively). | baseline; week 1 and 3 of sitagliptin monotherapy; week 1, 2, 4, 12 of triple therapy |
| Immunologic study | Frequency of CXCR3+ cells in circulation (monitored by FACS). | baseline, week 1 and 3 of sitagliptin monotherapy; week 1, 2, 4, 12 of triple therapy. |
| Créteil |
| 94010 |
| France |
| Henri Mondor Hospital | Créteil | 94010 | France |
| Cochin Hospital | Paris | 75014 | France |
| ID | Term |
|---|---|
| D006526 | Hepatitis C |
| D019698 | Hepatitis C, Chronic |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D006525 | Hepatitis, Viral, Human |
| D014777 | Virus Diseases |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D006521 | Hepatitis, Chronic |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000068900 | Sitagliptin Phosphate |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011719 | Pyrazines |
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