NCT00433069

Retreatment of Chronic Hepatitis C Non-responders With Pegylated Interferon Alpha Plus Ribavirin Plus Pioglitazone

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)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 5 (actual)
• Sponsor: University Hospital, Geneva · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

Insulin resistance and diabetes are major disease modifiers in chronic hepatitis C, as they increase liver fibrogenesis and reduce the rate of response to antivirals. Regarding the latter, a previous study showed that a sustained virological response (SVR) occurred in about one third of patients with genotype 1 and insulin resistance (measured as homeostasis assessment of insulin resistance, HOMA-IR \> 2) vs. two thirds of genotype 1 patients without insulin resistance. These findings were independently confirmed by other studies and extended to non-responders with genotypes 2, 3 and 4. Thus, we suggested that insulin resistance should be corrected in patients with chronic hepatitis C not responding to currently available antiviral treatment, in order to improve response to retreatment. The modalities of this intervention, however, have not been established. In addition, the optimal HOMA-IR score to be attained has not been identified. To assess this point, we planned a prospective, multicenter study to investigate the efficacy and safety of the insulin-sensitizer pioglitazone (ActosTM, Takeda Pharma AG, Lachen, Switzerland) 15 mg QD, added to the pegylated interferon-α2a (PEG-IFN-α2a) (PegasysTM, Roche Pharma Schweiz AG, Reinach, Switzerland) 180 μg QW/ribavirin (CopegusTM, Roche) 1000-1200 mg QD combination therapy in chronic hepatitis C patients who had previously failed to respond (i.e. had detectable serum HCV RNA after 12 weeks of therapy) to a pegylated interferon-α/ribavirin combination without the insulin-sensitizer. All patients had a baseline HOMA-IR score \>2 as additional inclusion criterion, because this was the threshold discriminating responders from non-responders in previous works. Diabetic patients were excluded.

Conditions

• Chronic Hepatitis C

Interventions

Type	Name	Description
DRUG	Pioglitazone	Increase early virological response to pegylated interferon alpha plus ribavirin by increasing insulin sensitivity
DRUG	Interferon Alfa-2a	Standard of care for chronic hepatitis C
DRUG	Ribavirin	Standard of care for chronic hepatitis C

Timeline

• Start date: 2007-01-01
• Primary completion: 2007-12-01
• Completion: 2008-01-01
• First posted: 2007-02-09
• Last updated: 2015-05-28

Locations

1 site across 1 country: Switzerland