Exploring the effect of disturbance in insulin metabolism on the treatment response of hepatitis C virus to find options to improve response rate

ISRCTN	ISRCTN64847145
DOI	https://doi.org/10.1186/ISRCTN64847145
EudraCT/CTIS number	2009-016678-34
Secondary identifying numbers	EudraCT No: 2009-016678-34

Submission date: 07/12/2009
Registration date: 15/01/2010
Last edited: 03/09/2014

Recruitment status: Stopped
Overall study status: Stopped
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Mark Thursz
Scientific

Hepatology Section
Imperial College
St Mary's Campus
Norfolk place
London
W2 1NY
United Kingdom

Phone	+44 (0)207 886 1903
Email	m.thursz@imperial.ac.uk

Study information

Study design	Prospective open-label study
Primary study design	Interventional
Secondary study design	Other
Study setting(s)	Hospital
Study type	Treatment
Scientific title	Exploring the relationship between insulin resistance and interferon resistance: options to overcome Hepatitis C Virus (HCV) non-response to pegylated interferon
Study objectives	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(s)	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
Health condition(s) or problem(s) studied	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
Primary outcome measure	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 study start date	01/02/2010
Completion date	31/01/2012
Reason abandoned (if study stopped)	Participant recruitment issue

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	22 patients
Key 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
Key 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
Date of first enrolment	01/02/2010
Date of final enrolment	31/01/2012

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Hepatology Section

London
W2 1NY
United Kingdom

Sponsor information

Imperial College London and Imperial College Healthcare NHS Trust (UK)
University/education

Joint Research Office
G02, Sir Alexander Fleming Building
South Kensington Campus
London
SW7 2AZ
England
United Kingdom

Phone	+44(0)20 7594 1554
Email	lucy.parker@imperial.ac.uk
Website	http://www3.imperial.ac.uk/
"ROR"	https://ror.org/041kmwe10

Funders

Funder type

University/education

Imperial College London (UK) - Hepatology Section

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan