- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00433069
Retreatment of Chronic Hepatitis C Non-responders With Pegylated Interferon Alpha Plus Ribavirin Plus Pioglitazone
May 27, 2015 updated by: Negro Francesco, University Hospital, Geneva
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)
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
5
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
GE
-
Geneva, GE, Switzerland, 1211
- Service de Gastroentérologie et d'Hépatologie, University Hospital
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
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:
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Intervention
Pioglitazone 15 mg QD + pegylated interferon Alfa-2a 180 μg QW + ribavirin 1000-1200 mg QD for 12 weeks, to be continued to a total of 48 weeks in case of complete early virological response, defined as undetectable serum HCV RNA after 12 weeks of triple therapy
|
Increase early virological response to pegylated interferon alpha plus ribavirin by increasing insulin sensitivity
Other Names:
Standard of care for chronic hepatitis C
Other Names:
Standard of care for chronic hepatitis C
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Early virological response
Time Frame: Week 12 of triple combined therapy
|
Week 12 of triple combined therapy
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Undetectable serum HCV RNA after 4, 24 weeks and 48 weeks of therapy
Time Frame: Week 2, 24 and 48 of therapy
|
Week 2, 24 and 48 of therapy
|
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
|
Weeks 4, 12 and 48 of therapy
|
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
|
Weeks 12 and 48 of therapy; week 24 of FU
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Francesco Negro, Prof, University of Geneva, Switzerland
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
January 1, 2007
Primary Completion (Actual)
December 1, 2007
Study Completion (Actual)
January 1, 2008
Study Registration Dates
First Submitted
February 8, 2007
First Submitted That Met QC Criteria
February 8, 2007
First Posted (Estimate)
February 9, 2007
Study Record Updates
Last Update Posted (Estimate)
May 28, 2015
Last Update Submitted That Met QC Criteria
May 27, 2015
Last Verified
May 1, 2015
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Liver Diseases
- Flaviviridae Infections
- Hepatitis, Viral, Human
- Enterovirus Infections
- Picornaviridae Infections
- Hepatitis
- Hepatitis A
- Hepatitis C
- Hepatitis, Chronic
- Hepatitis C, Chronic
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Antimetabolites
- Antineoplastic Agents
- Immunologic Factors
- Interferons
- Interferon-alpha
- Ribavirin
- Interferon alpha-2
- Pioglitazone
Other Study ID Numbers
- GE-DMI-05-116
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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