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Extrahepatic Insulin Resistance in Chronic Hepatitis C

Primary Purpose

Insulin Resistance

Status
Completed
Phase
Not Applicable
Locations
Switzerland
Study Type
Interventional
Intervention
Ledipasvir 90 mg/Sofosbuvir 400 mg
Ribavirin
Sponsored by
University Hospital, Geneva
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Insulin Resistance

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically confirmed chronic hepatitis C with HCV genotype 3a infection,
  • Adult Caucasian patient males or non-pregnant or non-lactating females, aged 18 to 65 at the time of the screening;
  • Informed Consent as documented by signature;
  • Lack of contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational products.

Exclusion Criteria:

  • Cirrhosis;
  • Excess active alcohol consumption (>30 g/day in males, >20 g/day in females);
  • Active illicit drug use.
  • Coinfection with HIV or hepatitis B virus;
  • Concomitant medications with clinically significant interactions with the study drugs;
  • Women who are pregnant or breast feeding or who intend to become pregnant during the course of the study;
  • Lack of safe contraception, defined as: female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases;
  • Other clinically significant concomitant disease states (e.g., renal failure, hepatic dysfunction, cardiovascular disease, etc.);
  • Known or suspected non-compliance;
  • Inability to follow the procedures of the study, including, but not limited to, language problems, psychological disorders, dementia;
  • Participation in another study with any investigational drug within the 30 days preceding and during the present study;
  • Enrolment of the investigator, his/her family members, employees and other dependent persons.

Sites / Locations

  • Division of Gastroenterology and hepatology, University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Active treatment

Arm Description

Ledipasvir 90 mg/Sofosbuvir 400 mg, one tablet once a day + b.w. dose adjusted, 200 mg-tablets of ribavirin (1,000 mg in two administration in patients <75 Kg of body weight, or 1,200 mg in two administrations for those >75 Kg) for 12 weeks

Outcomes

Primary Outcome Measures

Hepatitis C virus-induced insulin resistance
Increased (equal to or higher than 10% vs. basal) glucose consumption in patients with chronic hepatitis C but without the metabolic syndrome after complete suppression of viral replication induced by 6 weeks of treatment with Ledipasvir 90 mg/Sofosbuvir 400 mg and ribavirin, as measured by euglycemic hyperinsulinemic clamp using deuterated glucose, and compared to basal conditions i.e. before antiviral treatment.

Secondary Outcome Measures

Full Information

First Posted
April 30, 2016
Last Updated
April 29, 2019
Sponsor
University Hospital, Geneva
Collaborators
Gastaldi Giacomo, Clément Sophie
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1. Study Identification

Unique Protocol Identification Number
NCT02760355
Brief Title
Extrahepatic Insulin Resistance in Chronic Hepatitis C
Official Title
Hepatitis C Virus Infection Induced Insulin Resistance: Different Contribution From Liver and Extrahepatic Sites as Inferred by Treating Chronic Hepatitis C Patients With an Interferon-free Antiviral Combination
Study Type
Interventional

2. Study Status

Record Verification Date
April 2019
Overall Recruitment Status
Completed
Study Start Date
March 2016 (Actual)
Primary Completion Date
June 1, 2018 (Actual)
Study Completion Date
June 1, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital, Geneva
Collaborators
Gastaldi Giacomo, Clément Sophie

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
In this pilot study, the investigators plan to treat patients with chronic hepatitis C due to HCV genotype 3 infection using an interferon-free regimen consisting in the administration of ribavirin and sofosbuvir/ledipasvir - a combination of a nucleotide RNA polymerase inhibitor with a non-structural protein 5A inhibitor. Patients will undergo a euglycemic hyperinsulinemic clamp, using tracers, and indirect calorimetry to assess whether the viral suppression induced by this regimen will be capable of reversing the glucose metabolic alterations induced by HCV in both the liver and extrahepatic compartments. Adipose and muscle tissue biopsies will also be performed to assess some specific molecular changes induced by HCV.
Detailed Description
Epidemiological studies have shown that hepatitis C virus (HCV) infection induces insulin resistance, which may progress to type 2 diabetes in susceptible individuals. Despite the fact that HCV infects the liver, insulin resistance in these patients appears to originate mostly in extrahepatic tissues, particularly in muscles and adipose tissues. The aim of this trial is to assess the relative contribution of hepatic vs. extrahepatic tissues to the pathogenesis of insulin resistance in chronic hepatitis C. To do so, 20 patients will be enrolled in a single-arm, open-label study. Study subjects will include 10 patients without any feature of the metabolic syndrome, and another 10 with the metabolic syndrome. All patients will receive the same regimen consisting of Ledipasvir 90 mg/Sofosbuvir 400 mg, one tablet once a day, associated with body weight-dose adjusted, 200 mg-tablets of ribavirin (1,000 mg in two administration in patients <75 Kg of body weight, or 1,200 mg in two administrations for those >75 Kg) for 12 weeks. Insulin resistance will be investigated at baseline (before treatment) and after 6 weeks of treatment using a euglycemic hyperinsulinemic clamp with deuterated glucose: results obtained at 6 weeks - i.e. at the time of complete viral suppression - will be compared to basal conditions i.e. before antiviral treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Insulin Resistance

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
17 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Active treatment
Arm Type
Experimental
Arm Description
Ledipasvir 90 mg/Sofosbuvir 400 mg, one tablet once a day + b.w. dose adjusted, 200 mg-tablets of ribavirin (1,000 mg in two administration in patients <75 Kg of body weight, or 1,200 mg in two administrations for those >75 Kg) for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Ledipasvir 90 mg/Sofosbuvir 400 mg
Other Intervention Name(s)
Harvoni
Intervention Description
Oral administration on one fixed dose combination tablet for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Ribavirin
Other Intervention Name(s)
Rebetol
Intervention Description
Oral administration of body weight-dose adjusted, 200 mg-tablets of ribavirin (1,000 mg in two administration in patients <75 Kg of body weight, or 1,200 mg in two administrations for those >75 Kg) for 12 weeks.
Primary Outcome Measure Information:
Title
Hepatitis C virus-induced insulin resistance
Description
Increased (equal to or higher than 10% vs. basal) glucose consumption in patients with chronic hepatitis C but without the metabolic syndrome after complete suppression of viral replication induced by 6 weeks of treatment with Ledipasvir 90 mg/Sofosbuvir 400 mg and ribavirin, as measured by euglycemic hyperinsulinemic clamp using deuterated glucose, and compared to basal conditions i.e. before antiviral treatment.
Time Frame
6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed chronic hepatitis C with HCV genotype 3a infection, Adult Caucasian patient males or non-pregnant or non-lactating females, aged 18 to 65 at the time of the screening; Informed Consent as documented by signature; Lack of contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational products. Exclusion Criteria: Cirrhosis; Excess active alcohol consumption (>30 g/day in males, >20 g/day in females); Active illicit drug use. Coinfection with HIV or hepatitis B virus; Concomitant medications with clinically significant interactions with the study drugs; Women who are pregnant or breast feeding or who intend to become pregnant during the course of the study; Lack of safe contraception, defined as: female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases; Other clinically significant concomitant disease states (e.g., renal failure, hepatic dysfunction, cardiovascular disease, etc.); Known or suspected non-compliance; Inability to follow the procedures of the study, including, but not limited to, language problems, psychological disorders, dementia; Participation in another study with any investigational drug within the 30 days preceding and during the present study; Enrolment of the investigator, his/her family members, employees and other dependent persons.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Francesco Negro, MD
Organizational Affiliation
University Hospitals of Geneva
Official's Role
Principal Investigator
Facility Information:
Facility Name
Division of Gastroenterology and hepatology, University Hospital
City
Geneva
State/Province
GE
ZIP/Postal Code
1211
Country
Switzerland

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Scientific publication in a peer-reviewed journal

Learn more about this trial

Extrahepatic Insulin Resistance in Chronic Hepatitis C

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