Condition category
Infections and Infestations
Date applied
07/12/2009
Date assigned
15/01/2010
Last edited
03/09/2014
Prospective/Retrospective
Prospectively registered
Overall trial status
Stopped
Recruitment status
Stopped

Plain English Summary

Not provided at time of registration

Trial website

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

http://www3.imperial.ac.uk/

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

Publication citations

Additional files

Editorial Notes