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Trial record 61 of 538 for:    IFNA2 AND RBV AND Hepatitis

A Pilot Study Evaluating Safety of Sitagliptin Combined With Peg-IFN Alfa-2a + Ribavirin in Chronic Hepatitis C Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01567540
Recruitment Status : Terminated (New treatments available, which prevents additional recruitment.)
First Posted : March 30, 2012
Last Update Posted : January 20, 2014
Information provided by (Responsible Party):
Institut National de la Santé Et de la Recherche Médicale, France

Brief 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.

Condition or disease Intervention/treatment Phase
Hepatitis C Drug: Sitagliptin Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study to Evaluate the Clinical and Biological Tolerance of Sitagliptin With Pegylated Interferon alfa2a Plus Ribavirin Combination Therapy in Chronic Hepatitis C Patients
Study Start Date : March 2013
Actual Primary Completion Date : January 2014
Actual Study Completion Date : January 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: DPPIV Inhibition
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).
Drug: Sitagliptin
100 mg Sitagliptin daily for 15 weeks

Primary Outcome Measures :
  1. Safety (Number of adverse events, Toxicity grade > 3) [ Time Frame: After Day 1 until the end of the trial, i.e. a duration of 15 weeks for each patient ]

Secondary Outcome Measures :
  1. Change in Viral Load as compared to baseline [ Time Frame: week 1, 2, 3 of sitagliptin monotherapy; week 2, 4, 12 of triple therapy ]
  2. Metabolic studies: Oral glucose tolerance will be assessed [ Time Frame: baseline, week 1 of sitagliptin monotherapy; week 2 of triple therapy ]
  3. Immunologic study [ Time Frame: baseline, week 1 and 3 of sitagliptin monotherapy; week 1, 2, 4, 12 of triple therapy ]
    Monitoring the short and long form of IP-10 as compared to the total plasma concentration (three distinct ELISA assays).

  4. Immunologic study [ Time Frame: baseline; week 1 and 3 of sitagliptin monotherapy; week 1, 2, 4, 12 of triple therapy ]
    Plasma concentration and activity of DPPIV (measured using an ELISA and a luciferase-based bioassay, respectively).

  5. Immunologic study [ Time Frame: baseline, week 1 and 3 of sitagliptin monotherapy; week 1, 2, 4, 12 of triple therapy. ]
    Frequency of CXCR3+ cells in circulation (monitored by FACS).

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age between 18 and 70 years
  • For women, effective contraception during the trial and a negative pregnancy test (urine) before enrollment
  • Patients naïve to prior hepatitis C treatment
  • Confirmed HCV infection, based on the presence of HCV antibodies and plasma viremia allowing a measure of the circulating viral load
  • Infection with HCV genotype 1 or 4
  • Intent of treatment Alfa2 pegylated IFN-/ ribavirin

Exclusion Criteria:

  • HBV Infection
  • HIV Infection
  • Severe anemia (Hb <7-8 g / dl)
  • Renal failure (creatinine clearance <60 ml / min)
  • Taking digoxin within 6 months of starting treatment.
  • Taking immunosuppressants within 6 months of starting treatment
  • History of serious hypersensitivity reaction (such as anaphylactic shock or angioedema) to sitagliptin
  • Patients with type I and II diabetes
  • Pregnancy or absence of effective contraception
  • A person deprived of liberty by judicial or administrative decision
  • Living conditions-suggesting an inability to track all scheduled visits by the protocol

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01567540

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Centre Hospitalier Victor Dupuy
Argenteuil, France, 95100
Centre Hospitalier Intercommunal Créteil
Créteil, France, 94010
Henri Mondor Hospital
Créteil, France, 94010
Cochin Hospital
Paris, France, 75014
Sponsors and Collaborators
Institut National de la Santé Et de la Recherche Médicale, France
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Principal Investigator: Matthew L. ALBERT, MD, PhD Institut National de la Santé Et de la Recherche Médicale, France

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Responsible Party: Institut National de la Santé Et de la Recherche Médicale, France Identifier: NCT01567540     History of Changes
Other Study ID Numbers: C10-54
2011-000823-34 ( EudraCT Number )
First Posted: March 30, 2012    Key Record Dates
Last Update Posted: January 20, 2014
Last Verified: January 2014
Keywords provided by Institut National de la Santé Et de la Recherche Médicale, France:
Chronic Hepatitis C
Interferon protein 10
Chemokine gradients
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis, Chronic
Hepatitis, Viral, Human
Liver Diseases
Digestive System Diseases
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Sitagliptin Phosphate
Peginterferon alfa-2a
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors