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ISRCTN
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ISRCTN64847145
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ClinicalTrials.gov identifier
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Public title
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Exploring the effect of disturbance in insulin metabolism on the treatment response of hepatitis c virus to find options to improve response rate
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Scientific title
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Exploring the relationship between Insulin resistance and interferon resistance: options to overcome Hepatitis C Virus (HCV) non-response to pegylated interferon
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Acronym
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N/A
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Serial number at source
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Eudract No: 2009-016678-34
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Study hypothesis
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Hepatitis C virus (HCV) infection is a serious problem. Currently, pegylated interferon and ribavirin treatment can result in cure. However, the average overall cure rate is about 55% of patients. This average depends on the viral genotypes (substrains). For example, cure rate is lower in HCV genotype 1 and 4 than HCV genotype 2 and 3. In addition, patients with liver cirrhosis (scarring) have lower chance to respond to treatment. Furthermore, there is a new scientific evidence that disturbance in insulin metabolism which is called insulin resistance may lower the treatment response. Insulin resistance can be caused by obesity and/or diabetes mellitus (DM). Now, there is new evidence that HCV per se can cause insulin resistance. This means that any patient with HCV infection could have insulin resistance even if he/she is non-obese and non-diabetic. As insulin resistance can decrease the chance of cure in response to current treatment, so improving insulin resistance may improve the treatment response and overall cure rate. Insulin resistance can be improved by pioglitazone oral tablets treatment which is currently used for patients with DM.
The objective of this study is to improve the overall cure rate in response to treatment by pegylated interferon and ribavirin by addition of pioglitazone to improve insulin resistance.
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Lay summary
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Ethics approval
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Ethical approval is in progress. Within December 2010, will apply to:
1. Medicines and Healthcare products Regulatory Agency (MHRA)
2. NHS / Health and Social Care (HSC) R&D office
3. Social Care Research Ethics Committee
4. NHS Ssci
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Study design
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Prospective open label study
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Countries of recruitment
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United Kingdom
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Disease/condition/study domain
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Hepatitis C Virus (HCV) infection
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Participants - inclusion criteria
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1. Chronic HCV genotype 1 infection
2. Chronic HCV and compensated liver cirrhosis who failed to respond to previous treatment.
3. Age >17, <70
4. Eligible for interferon therapy
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Participants - exclusion criteria
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1. HIV or HBV co-infection.
2. Current use antidiabetic medication (eg insulin, metformin or thiazolidinedione).
3. Significant respiratory, cardiac or renal dysfunction
4. Body Mass Index > 30 kg/m2
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Anticipated start date
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01/02/2010
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Anticipated end date
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31/01/2012
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Status of trial
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Completed |
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Patient information material
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Target number of participants
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22 patients
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Interventions
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In stage 1, we will investigate the physiologic response to pioglitazone therapy by comparing measured total insulin resistance, hepatic insulin resistance, interferon sensitivity and virologic response before and after a 12 week course of pioglitazone.
The total duration of follow-up for stage I will be 13 weeks.
In stage 2, pioglitazone 30mg will be added to standard therapy for two groups of patients: a) group I consisted of naïve patients with HCV genotype 1 infection and b) group II consisted of patients with hepatitis C and compensated liver cirrhosis (Ishak fibrosis score ≥5) who failed to respond to previous treatment. The impact of adding pioglitazone to standard treatment on sustained virologic response (SVR) will be determined after a full course of pegylated interferon and ribavirin treatment in addition to pioglitazone therapy.
The total duration of follow-up for stage II will be 1.5 years.
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Primary outcome measure(s)
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Insulin resistance:
Total body insulin resistance and hepatic insulin resistance will be measured using the hyperinsulinaemic euglycaemic clamp.
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Secondary outcome measure(s)
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1. Interferon sensitivity (Interferon-Inducible Protein [IP10] in blood measured by ELISA and in peripheral blood mononuclear cells [PBMC] by mRNA)
2. Viral dynamic response measured by serial HCV PCR levels
3. Treatment response measured by serial HCV PCR levels
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Sources of funding
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Imperial College London (UK) - Hepatology Section
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Trial website
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Publications
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Contact name
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Prof
Mark
Thursz
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Address
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Hepatology Section
Imperial College
St Mary's Campus
Norfolk place
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City/town
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London
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Zip/Postcode
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W2 1NY
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Country
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United Kingdom
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Tel
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+44 (0)207 886 1903
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Fax
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+44(0)207 706 9161
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Email
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m.thursz@imperial.ac.uk
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Sponsor
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Imperial College London and Imperial College Healthcare NHS Trust (UK)
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Address
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Joint Research Office
G02, Sir Alexander Fleming Building
South Kensington Campus
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City/town
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London
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Zip/Postcode
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SW7 2AZ
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Country
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United Kingdom
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Tel
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+44(0)20 7594 1554
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Fax
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+44(0)20 7594 1792
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Email
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lucy.parker@imperial.ac.uk
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Sponsor website:
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http://www3.imperial.ac.uk/
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Date applied
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07/12/2009
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Last edited
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17/11/2010
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Date ISRCTN assigned
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15/01/2010
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