Retreatment of Chronic Hepatitis C Non-Responders With Pegylated Interferon Alpha Plus Ribavirin Plus Pioglitazone - Full Text View

Sponsor:	University Hospital, Geneva
Information provided by:	University Hospital, Geneva
ClinicalTrials.gov Identifier:	NCT00433069

Purpose

The aim of this study is to investigate the efficacy and safety of an insulin-sensitizer (Actos) added to a standard Pegasys/Copegus combination therapy of chronic hepatitis C in patients who have previously failed a pegylated-interferon-alpha / ribavirin combination without the insulin sensitizer. The primary endpoint is the initial virological response (level of HCV RNA in serum) as evaluated after 12 weeks of triple therapy.

Condition	Intervention	Phase
Chronic Hepatitis C	Drug: Pioglitazone Drug: Increase response to interferon alpha plus ribavirin by increasing insulin sensitivity	Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Pilot Study of Treatment With Pegylated Interferon-Alpha2a, Ribavirin and Insulin Sensitizer Pioglitazone of Insulin Resistance (With the Exception of Diabetes) in Hepatitis C Virus Infection (The INSPIRED HCV Study)

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis C

Drug Information available for: Insulin Ribavirin Interferon alfa-2a Pioglitazone Pioglitazone hydrochloride Peginterferon Alfa-2a Interferon alfa-n1 Interferons

U.S. FDA Resources

Further study details as provided by University Hospital, Geneva:

Primary Outcome Measures:

Early virological response [ Time Frame: Week 12 of triple combined therapy ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Undetectable serum HCV RNA after 4, 24 weeks and 48 weeks of therapy [ Time Frame: Week 2, 24 and 48 of therapy ] [ Designated as safety issue: Yes ]
Changes (vs. baseline) of body weight, HOMA score, after 4, 12 and 48 weeks of therapy and after 24 weeks of follow-up [ Time Frame: Weeks 4, 12 and 48 of therapy ] [ Designated as safety issue: Yes ]
Improvement (vs. baseline) of glucose tolerance parameters after 12 and 48 weeks of therapy and after 24 weeks of follow-up [ Time Frame: Weeks 12 and 48 of therapy; week 24 of FU ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	35
Study Start Date:	January 2007
Estimated Study Completion Date:	July 2007
Primary Completion Date:	July 2007 (Final data collection date for primary outcome measure)

Intervention Details:

Increase response to interferon alpha plus ribavirin by increasing insulin sensitivity

Pioglitazone 15 mg PD will be given to chronic hepatitis C patients in addition to peginterferon-alpha2a and ribavirin (Standard of Care, SOC) for 12 weeks to improve virological response. All recruited patients will be previous non-responders to SOC.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histologically confirmed chronic hepatitis C as per liver biopsy performed during the 12 months prior to enrollment (except patients with histologically proven cirrhosis or a Actitest/Fibrotest assay, or a Fibroscan performed during the 12 months prior to enrollment)
HCV RNA in serum >600 IU/ml
elevated ALT
HCV genotypes 1, 2, 3 or 4
failure to respond to a prior treatment with a pegylated interferon alpha + ribavirin
HOMA score > 2.00
documentation that sexually active female patients of childbearing potential are practicing adequate contraception (intrauterine device, oral contraceptives, progesterone implanted rods, medroxyprogesterone acetate, surgical sterilization plus a barrier method [diaphragm + spermicide] or monogamous relationship with a male partner who has had a vasectomy or is using a condom + spermicide) during the treatment period and for 6 months after discontinuation of therapy. A serum pregnancy test obtained at entry prior to the initiation of treatment must be negative. Female patients must not be breast feeding
documentation that sexually active male patients are practicing acceptable methods of contraception (vasectomy, use of a condom + spermicide, monogamous relationship with a female partner who practices an acceptable method of contraception) during the treatment period and for 6 months after discontinuation of therapy
willingness and capability to give written informed consent and to comply with the requirements of the trial

Exclusion Criteria:

history of diabetes (ADA definition)
history of significant cardiovascular disease (NYHA III) including but not limited to uncontrolled hypertension, angina pectoris, myocardial infarction, coronary artery surgery and congestive heart failure
HBsAg and/or HIV
auto-immune disease, including auto-immune hepatitis
alcohol consumption exceeding 40 grams per day
hepatocellular carcinoma
renal insufficiency (serum creatinine levels above 200 micromol/l)
unconjugated bilirubin blood level > 100 micromol/l
glutamyl transferase > 20 times the ULN
prothrombin time < 60% of control (except in case of oral anti-coagulant therapy)
neutrophil count < 1.5 G/L
platelet count < 70 G/L
hemoglobin <120 g/L
organ or bone marrow transplantation
current neoplasm and/or anti-tumor chemotherapy
current hepatic arterial thrombosis
pregnant or breast feeding women; child bearing potential women without adequate contraception throughout the course of therapy
psychosis or anti-depressant therapy for uncontrolled clinical depression
epilepsy
clinically significant retinal abnormalities
thyroid dysfunction
drug abuse or substitution therapy during the 12 months prior to inclusion
interstitial pneumonitis
previous auto-immune hemolysis and all causes of chronic hemolysis

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00433069

Locations

Switzerland, GE
Service de Gastroentérologie et d'Hépatologie, University Hospital
Geneva, GE, Switzerland, 1211

Sponsors and Collaborators

University Hospital, Geneva

Investigators

Principal Investigator:

Francesco Negro, Prof

University of Geneva, Switzerland

More Information

Publications:

Romero-Gomez M, Del Mar Viloria M, Andrade RJ, Salmeron J, Diago M, Fernandez-Rodriguez CM, Corpas R, Cruz M, Grande L, Vazquez L, Munoz-De-Rueda P, Lopez-Serrano P, Gila A, Gutierrez ML, Perez C, Ruiz-Extremera A, Suarez E, Castillo J. Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients. Gastroenterology. 2005 Mar;128(3):636-41.

Responsible Party:	University Hospital of Geneva ( Prof. Francesco Negro )
Study ID Numbers:	GE-DMI-05-116, The SASL 22 Study
Study First Received:	February 8, 2007
Last Updated:	April 10, 2008
ClinicalTrials.gov Identifier:	NCT00433069 History of Changes
Health Authority:	Switzerland: Swissmedic

Keywords provided by University Hospital, Geneva:

Chronic hepatitis C
Insulin resistance
Pioglitazone
Non-responders
Chronic hepatitis C that has previously failed to respond to a pegylated-interferon-alpha / ribavirin combination

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Liver Diseases
Interferon Type I, Recombinant
Molecular Mechanisms of Pharmacological Action
Flaviviridae Infections
Hepatitis, Chronic
Pioglitazone
Immunologic Factors
Antineoplastic Agents
Ribavirin
Physiological Effects of Drugs
Hepatitis, Viral, Human
Insulin
Hyperinsulinism

Hypoglycemic Agents
Therapeutic Uses
Growth Inhibitors
Angiogenesis Modulating Agents
Hepatitis C
Interferon-alpha
RNA Virus Infections
Metabolic Diseases
Growth Substances
Interferons
Angiogenesis Inhibitors
Antiviral Agents
Pharmacologic Actions
Virus Diseases
Hepatitis

ClinicalTrials.gov processed this record on February 09, 2010