Contact information
Type
Scientific
Primary contact
Prof Mark Thursz
ORCID ID
Contact details
Hepatology Section
Imperial College
St Mary's Campus
Norfolk place
London
W2 1NY
United Kingdom
+44 (0)207 886 1903
m.thursz@imperial.ac.uk
Additional identifiers
EudraCT number
2009-016678-34
ClinicalTrials.gov number
Protocol/serial number
EudraCT No: 2009-016678-34
Study information
Scientific title
Exploring the relationship between insulin resistance and interferon resistance: options to overcome Hepatitis C Virus (HCV) non-response to pegylated interferon
Acronym
Study hypothesis
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, the cure rate is lower in HCV genotype 1 and 4 than HCV genotype 2 and 3. In addition, patients with liver cirrhosis (scarring) have a lower chance to respond to treatment. Furthermore, there is 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.
Ethics approval
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
Study design
Prospective open-label study
Primary study design
Interventional
Secondary study design
Other
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Hepatitis C Virus (HCV) infection
Intervention
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 30 mg 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.
Updated 03/09/2014: the trial was stopped in 2011 due to poor recruitment.
Intervention type
Other
Phase
Not Applicable
Drug names
Primary outcome measures
Insulin resistance:
Total body insulin resistance and hepatic insulin resistance will be measured using the hyperinsulinaemic euglycaemic clamp.
Secondary outcome measures
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
Overall trial start date
01/02/2010
Overall trial end date
31/01/2012
Reason abandoned
Participant recruitment issue
Eligibility
Participant inclusion criteria
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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
22 patients
Participant exclusion criteria
1. HIV or HBV co-infection
2. Current use antidiabetic medication (e.g., insulin, metformin or thiazolidinedione)
3. Significant respiratory, cardiac or renal dysfunction
4. Body Mass Index > 30 kg/m2
Recruitment start date
01/02/2010
Recruitment end date
31/01/2012
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Hepatology Section
London
W2 1NY
United Kingdom
Sponsor information
Organisation
Imperial College London and Imperial College Healthcare NHS Trust (UK)
Sponsor details
Joint Research Office
G02
Sir Alexander Fleming Building
South Kensington Campus
London
SW7 2AZ
United Kingdom
+44(0)20 7594 1554
lucy.parker@imperial.ac.uk
Sponsor type
University/education
Website
Funders
Funder type
University/education
Funder name
Imperial College London (UK) - Hepatology Section
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary