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Trial record 54 of 115 for:    "Viral Infectious Disease" | "Ledipasvir"

Extrahepatic Insulin Resistance in Chronic Hepatitis C

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ClinicalTrials.gov Identifier: NCT02760355
Recruitment Status : Completed
First Posted : May 3, 2016
Last Update Posted : May 1, 2019
Sponsor:
Collaborators:
Gastaldi Giacomo
Clément Sophie
Information provided by (Responsible Party):
Negro Francesco, University Hospital, Geneva

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.

Condition or disease Intervention/treatment Phase
Insulin Resistance Drug: Ledipasvir 90 mg/Sofosbuvir 400 mg Drug: Ribavirin Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
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
Actual Study Start Date : March 2016
Actual Primary Completion Date : June 1, 2018
Actual Study Completion Date : June 1, 2018

Resource links provided by the National Library of Medicine


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
Drug: Ledipasvir 90 mg/Sofosbuvir 400 mg
Oral administration on one fixed dose combination tablet for 12 weeks
Other Name: Harvoni

Drug: Ribavirin
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 Name: Rebetol




Primary Outcome Measures :
  1. 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.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02760355


Locations
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Switzerland
Division of Gastroenterology and hepatology, University Hospital
Geneva, GE, Switzerland, 1211
Sponsors and Collaborators
University Hospital, Geneva
Gastaldi Giacomo
Clément Sophie
Investigators
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Principal Investigator: Francesco Negro, MD University Hospitals of Geneva

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Responsible Party: Negro Francesco, Professor, University Hospital, Geneva
ClinicalTrials.gov Identifier: NCT02760355     History of Changes
Other Study ID Numbers: 15-063
First Posted: May 3, 2016    Key Record Dates
Last Update Posted: May 1, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Scientific publication in a peer-reviewed journal
Additional relevant MeSH terms:
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Virus Diseases
RNA Virus Infections
Ledipasvir
Hepatitis C
Hepatitis C, Chronic
Hepatitis
Insulin Resistance
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Flaviviridae Infections
Hepatitis, Chronic
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Ribavirin
Sofosbuvir
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents