High Dose Insulin Therapy to Improve Liver Function

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

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.

Study Overview

• Status: Unknown
• Conditions: Hepatitis C Virus
• Intervention / Treatment: Drug: Insulin

• Study Type: Interventional
• Enrollment (Anticipated): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
      • McGill University Helath Centre - (Royal Victoria Hospital)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Insulin/dextrose clamp	Drug: Insulin; 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.; Other Names: Hyperinsulinemic normoglycemic clamp

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Insulin resistance	6 months
Inflammatory mediators	6 months

Collaborators and Investigators

• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Investigators: Principal Investigator: Peter Metrakos, MD, McGill University Health Centre/Research Institute of the McGill University Health Centre

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Anticipated): December 1, 2013
• Study Completion (Anticipated): June 1, 2014

Study Registration Dates

• First Submitted: January 5, 2011
• First Submitted That Met QC Criteria: January 5, 2011
• First Posted (Estimate): January 6, 2011

Study Record Updates

• Last Update Posted (Estimate): November 13, 2013
• Last Update Submitted That Met QC Criteria: November 11, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Hepatitis C; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: 10-086-BMA