Pioglitazone vs. Placebo in Association With Pegylated Interferon and Ribavirin in HCV Patients With Insulin Resistance (PEGLIST C)

ANRS HC 22, PEGLIST-C, Multicenter, Randomized Controlled Trial of Pioglitazone vs. Placebo in Association With Pegylated Interferon and Ribavirin in Patients With Chronic Hepatitis C, Non 2 or 3 Genotypes and Insulin Resistance

The purpose of this study is to test whether the correction of insulin resistance with pioglitazone, will improve the response to antiviral treatment.

Study Overview

• Status: Terminated
• Conditions: Insulin Resistance; Chronic Hepatitis C
• Intervention / Treatment: Drug: Pioglitazone; Drug: Placebo

Detailed Description

In patients infected with genotypes 1, 4, 5 and 6, the response rate to antiviral therapy remains suboptimal (less than one in two patients have a sustained virological response), which justifies the search for strategies optimizing the results of antiviral therapy. Some factors associated with non response have been identified. Among the modifiable factors, numerous series have shown that insulin resistance adversely impacts the rate of sustained virological response. The aim of this study is to determine whether the pharmacological correction of insulin resistance through therapy with glitazones restores higher rates of viral eradication and to determine the impact on the kinetics of viral response. Patients will be randomized to receive pioglitazone or placebo starting 4 months before initiating pegylated interferon and ribavirin and continued throughout the whole antiviral treatment period.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • Hôpital Pitié Salpêtrière, Service d'hépatogastroentérologie

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 18 years old or older
• Chronic HCV infection documented by PCR with genotype HCV-1, 4, 5 or 6
• Naive Patient(never treated with antivirals for HCV)
• HOMA score higher than 2.5
• Patient for which the investigator decided to start antiviral treatment for chronic hepatitis C

Exclusion Criteria:

• Cardiovascular disease: heart failure stage NYHA II, III or IV, unstable angina, myocardial infarction in the previous year, cardiac surgery or stroke
• Alcohol consumption exceeding 40 g / day
• Decompensated liver disease: Child-Pugh B 8 or higher, or one of the following : bilirubin over 35 mol / L, TP below 50%, ascites, encephalopathy
• Hepatocellular carcinoma or any other neoplasm (except if in remission for > 5 years)
• Other documented chronic liver disease
• Insulin treated diabetes
• HBV or HIV co-infection infection confirmed
• Thrombocytopenia below 50 000/mm ³; neutropenia below 750/mm ³ or hemoglobin below 11 g / dL
• Drug-induced steatosis(tamoxifen, glucocorticosteroids, amiodarone, tetracyclines).
• Bone marrow or solid organ transplantation
• Pregnancy or breastfeeding, or desire for pregnancy during the study period.
• Patients under legal protection or unable to express their consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; Pioglitazone, 16 weeks before and during antiviral combination therapy	Drug: Pioglitazone; Pioglitazone, 45 mg QD (30 mg QD the first month)
Placebo Comparator: 2; Pioglitazone placebo, 16 weeks before and during antiviral combination therapy	Drug: Placebo; Placebo 45 mg QD (30 mg QD the first month)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Decrease in the HOMA score below 2 after 4 months of treatment with pioglitazone or placebo(at W16). The efficiency is defined as a higher proportion of subjects with HOMA <2 in the pioglitazone group than in the group treated with placebo pioglitazone.	W16

Secondary Outcome Measures

Outcome Measure	Time Frame
Kinetics of decrease in viral response to pegylated interferon. Early virological response rates. Rates of sustained virological response. Effect on steatosis	EVR at W16 and W28 SVR at W88

Collaborators and Investigators

• Sponsor: French National Agency for Research on AIDS and Viral Hepatitis
• Investigators: Principal Investigator: Vlad RATZIU, MD, PHD, Hôpital Pitié--Salpêtrière, 83 Bd de l'Hôpital 75651 Paris cedex 13, FRANCE

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2009
• Primary Completion (Actual): July 6, 2012
• Study Completion (Actual): July 6, 2012

Study Registration Dates

• First Submitted: June 22, 2009
• First Submitted That Met QC Criteria: June 23, 2009
• First Posted (Estimate): June 24, 2009

Study Record Updates

• Last Update Posted (Estimate): January 24, 2017
• Last Update Submitted That Met QC Criteria: January 23, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: hepatitis C; insulin resistance; glitazones; pioglitazone; steatosis; viral kinetics; antiviral response
• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hyperinsulinism; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis, Chronic; Insulin Resistance; Hepatitis C, Chronic; Hypoglycemic Agents; Physiological Effects of Drugs; Pioglitazone
• Other Study ID Numbers: 2008-006225-14