- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02760355
Extrahepatic Insulin Resistance in Chronic Hepatitis C
April 29, 2019 updated by: Negro Francesco, University Hospital, Geneva
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
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
17
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
GE
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Geneva, GE, Switzerland, 1211
- Division of Gastroenterology and hepatology, University Hospital
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Active treatment
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
|
Oral administration on one fixed dose combination tablet for 12 weeks
Other Names:
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Hepatitis C virus-induced insulin resistance
Time Frame: 6 weeks
|
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.
|
6 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Francesco Negro, MD, University Hospitals of Geneva
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 1, 2016
Primary Completion (Actual)
June 1, 2018
Study Completion (Actual)
June 1, 2018
Study Registration Dates
First Submitted
April 30, 2016
First Submitted That Met QC Criteria
May 2, 2016
First Posted (Estimate)
May 3, 2016
Study Record Updates
Last Update Posted (Actual)
May 1, 2019
Last Update Submitted That Met QC Criteria
April 29, 2019
Last Verified
April 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Glucose Metabolism Disorders
- Metabolic Diseases
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Liver Diseases
- Flaviviridae Infections
- Hepatitis, Viral, Human
- Hepatitis, Chronic
- Hyperinsulinism
- Hepatitis
- Hepatitis C
- Insulin Resistance
- Hepatitis C, Chronic
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Antimetabolites
- Sofosbuvir
- Ribavirin
- Ledipasvir
Other Study ID Numbers
- 15-063
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
Scientific publication in a peer-reviewed journal
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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