High Dose Insulin Therapy to Improve Liver Function

Study Overview
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Brief Summary
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Insulin resistance is one of the key factors in defining a progressive course of chronic Hepatitis C virus (HCV) infection and hepatic fibrosis. Multiple trials have targeted insulin resistance as an adjuvant way to manage hepatitis C liver disease with promising results. Long term therapy using high dose insulin was shown to significantly reduce insulin resistance in obese patients. In cardiac and critically ill patients, long term insulin was shown to produce better outcomes mainly by reducing the overt inflammatory response. Furthermore, initial results of ongoing trials are revealing more benefits of insulin therapy. Using the (hyperinsulinimic normoglycemic clamp) for eight hours on patients undergoing major liver resection was able to maximize their liver function post-operatively. This trial also demonstrated inhibition of the inflammatory response, improvement in liver glycogen, inhibition of apoptosis and stimulation of liver regeneration. Putting in mind the potential ability of the liver to regenerate and regain better function. The anti-inflammatory properties of insulin therapy along with its ability to reduce insulin resistance over time has led us to see the potential benefits of using insulin therapy on patients with chronic hepatitis C virus liver cirrhosis. Insulin will target the pathophysiology of the disease at a cellular and a molecular level. The investigators theorize that long-term high insulin therapy would be able to promote better liver function and slow down fibrosis and injury in this population of patients.

Official Title
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High Dose Insulin Therapy to Improve Liver Function in Patients With HCV Liver Cirrhosis

Conditions
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Hepatitis C Virus

Intervention / Treatment
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* Drug: Insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hepatitis C positive adult patients (serum HCV antibody positive) MELD score 6-15 at the time of inclusion Viral genotype non-3 Not on antiviral therapy Exclusion Criteria: HBV or HIV co-infection Evidence of hepatocellular carcinoma at the start of the trial either by imaging and or AFP levels above 400 Undetectable HCV viral load (using HCV PCR test) Recent infection or bleeding (in the last 3 months)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Insulin/dextrose clamp<br> | Drug: Insulin<br>* Intravenous insulin clamp at a rate of 2 mlu/kg/hr. In adition a titrating dose of 20% dextrose aiming to a blood glucose level of 4 - 5.5 mmol/l.<br>* Other names: Hyperinsulinemic normoglycemic clamp;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver status improvments (biochemical and histological) |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin resistance |  | 6 months | 
| Inflammatory mediators |  | 6 months |