Ignite Creation Date:
2025-12-24 @ 11:11 PM
Ignite Modification Date:
2025-12-25 @ 8:44 PM
Study NCT ID:
NCT00433069
Status:
COMPLETED
Last Update Posted:
2015-05-28
First Post:
2007-02-08
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Retreatment of Chronic Hepatitis C Non-responders With Pegylated Interferon Alpha Plus Ribavirin Plus Pioglitazone
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D019698', 'term': 'Hepatitis C, Chronic'}, {'id': 'D007333', 'term': 'Insulin Resistance'}], 'ancestors': [{'id': 'D006526', 'term': 'Hepatitis C'}, {'id': 'D000086982', 'term': 'Blood-Borne Infections'}, {'id': 'D003141', 'term': 'Communicable Diseases'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D006525', 'term': 'Hepatitis, Viral, Human'}, {'id': 'D014777', 'term': 'Virus Diseases'}, {'id': 'D018178', 'term': 'Flaviviridae Infections'}, {'id': 'D012327', 'term': 'RNA Virus Infections'}, {'id': 'D006521', 'term': 'Hepatitis, Chronic'}, {'id': 'D006505', 'term': 'Hepatitis'}, {'id': 'D008107', 'term': 'Liver Diseases'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D002908', 'term': 'Chronic Disease'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D006946', 'term': 'Hyperinsulinism'}, {'id': 'D044882', 'term': 'Glucose Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077205', 'term': 'Pioglitazone'}, {'id': 'D000077190', 'term': 'Interferon alpha-2'}, {'id': 'C100416', 'term': 'peginterferon alfa-2a'}, {'id': 'D012254', 'term': 'Ribavirin'}], 'ancestors': [{'id': 'D045162', 'term': 'Thiazolidinediones'}, {'id': 'D013844', 'term': 'Thiazoles'}, {'id': 'D013457', 'term': 'Sulfur Compounds'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D016898', 'term': 'Interferon-alpha'}, {'id': 'D007370', 'term': 'Interferon Type I'}, {'id': 'D007372', 'term': 'Interferons'}, {'id': 'D016207', 'term': 'Cytokines'}, {'id': 'D036341', 'term': 'Intercellular Signaling Peptides and Proteins'}, {'id': 'D010455', 'term': 'Peptides'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D001685', 'term': 'Biological Factors'}, {'id': 'D012263', 'term': 'Ribonucleosides'}, {'id': 'D009705', 'term': 'Nucleosides'}, {'id': 'D009706', 'term': 'Nucleic Acids, Nucleotides, and Nucleosides'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 5}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2007-01'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2015-05', 'completionDateStruct': {'date': '2008-01', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2015-05-27', 'studyFirstSubmitDate': '2007-02-08', 'studyFirstSubmitQcDate': '2007-02-08', 'lastUpdatePostDateStruct': {'date': '2015-05-28', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2007-02-09', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2007-12', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Early virological response', 'timeFrame': 'Week 12 of triple combined therapy'}], 'secondaryOutcomes': [{'measure': 'Undetectable serum HCV RNA after 4, 24 weeks and 48 weeks of therapy', 'timeFrame': 'Week 2, 24 and 48 of therapy'}, {'measure': 'Changes (vs. baseline) of body weight, HOMA score, after 4, 12 and 48 weeks of therapy and after 24 weeks of follow-up', 'timeFrame': 'Weeks 4, 12 and 48 of therapy'}, {'measure': 'Improvement (vs. baseline) of glucose tolerance parameters after 12 and 48 weeks of therapy and after 24 weeks of follow-up', 'timeFrame': 'Weeks 12 and 48 of therapy; week 24 of FU'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Chronic hepatitis C', 'Insulin resistance', 'Pioglitazone', 'Non-responders'], 'conditions': ['Chronic Hepatitis C']}, 'referencesModule': {'references': [{'pmid': '15765399', 'type': 'BACKGROUND', 'citation': '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. doi: 10.1053/j.gastro.2004.12.049.'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* 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)\n* HCV RNA in serum \\>600 IU/ml\n* elevated ALT\n* HCV genotypes 1, 2, 3 or 4\n* failure to respond to a prior treatment with a pegylated interferon alpha + ribavirin\n* HOMA score \\> 2.00\n* 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\n* 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\n* willingness and capability to give written informed consent and to comply with the requirements of the trial\n\nExclusion Criteria:\n\n* history of diabetes (ADA definition)\n* 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\n* HBsAg and/or HIV\n* auto-immune disease, including auto-immune hepatitis\n* alcohol consumption exceeding 40 grams per day\n* hepatocellular carcinoma\n* renal insufficiency (serum creatinine levels above 200 micromol/l)\n* unconjugated bilirubin blood level \\> 100 micromol/l\n* glutamyl transferase \\> 20 times the ULN\n* prothrombin time \\< 60% of control (except in case of oral anti-coagulant therapy)\n* neutrophil count \\< 1.5 G/L\n* platelet count \\< 70 G/L\n* hemoglobin \\<120 g/L\n* organ or bone marrow transplantation\n* current neoplasm and/or anti-tumor chemotherapy\n* current hepatic arterial thrombosis\n* pregnant or breast feeding women; child bearing potential women without adequate contraception throughout the course of therapy\n* psychosis or anti-depressant therapy for uncontrolled clinical depression\n* epilepsy\n* clinically significant retinal abnormalities\n* thyroid dysfunction\n* drug abuse or substitution therapy during the 12 months prior to inclusion\n* interstitial pneumonitis\n* previous auto-immune hemolysis and all causes of chronic hemolysis'}, 'identificationModule': {'nctId': 'NCT00433069', 'briefTitle': 'Retreatment of Chronic Hepatitis C Non-responders With Pegylated Interferon Alpha Plus Ribavirin Plus Pioglitazone', 'organization': {'class': 'OTHER', 'fullName': 'University Hospital, Geneva'}, 'officialTitle': '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)', 'orgStudyIdInfo': {'id': 'GE-DMI-05-116'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Intervention', 'description': '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', 'interventionNames': ['Drug: Pioglitazone', 'Drug: Interferon Alfa-2a', 'Drug: Ribavirin']}], 'interventions': [{'name': 'Pioglitazone', 'type': 'DRUG', 'otherNames': ['Actos'], 'description': 'Increase early virological response to pegylated interferon alpha plus ribavirin by increasing insulin sensitivity', 'armGroupLabels': ['Intervention']}, {'name': 'Interferon Alfa-2a', 'type': 'DRUG', 'otherNames': ['Pegasys'], 'description': 'Standard of care for chronic hepatitis C', 'armGroupLabels': ['Intervention']}, {'name': 'Ribavirin', 'type': 'DRUG', 'otherNames': ['Copegus'], 'description': 'Standard of care for chronic hepatitis C', 'armGroupLabels': ['Intervention']}]}, 'contactsLocationsModule': {'locations': [{'zip': '1211', 'city': 'Geneva', 'state': 'Canton of Geneva', 'country': 'Switzerland', 'facility': "Service de Gastroentérologie et d'Hépatologie, University Hospital", 'geoPoint': {'lat': 46.20222, 'lon': 6.14569}}], 'overallOfficials': [{'name': 'Francesco Negro, Prof', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Geneva, Switzerland'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University Hospital, Geneva', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor', 'investigatorFullName': 'Negro Francesco', 'investigatorAffiliation': 'University Hospital, Geneva'}}}}