Extrahepatic Insulin Resistance in Chronic Hepatitis C

NCT02760355 | Completed DMC

• 1 other identifier: 15-063
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

Insulin Resistance

Outcome Measures

Primary Outcomes (1)

• 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.

  6 weeks

Study Arms (1)

Active treatment

EXPERIMENTAL

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; Drug: Ribavirin

Interventions

Ledipasvir 90 mg/Sofosbuvir 400 mg DRUG

Oral administration on one fixed dose combination tablet for 12 weeks

Also known as: Harvoni

Active treatment

Ribavirin DRUG

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.

Also known as: Rebetol

Active treatment

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Geneva: lead
• Gastaldi Giacomo: collaborator
• Clément Sophie: collaborator

Study Sites (1)

Division of Gastroenterology and hepatology, University Hospital

Geneva, Canton of Geneva, 1211, Switzerland

Location

MeSH Terms

Conditions

Insulin Resistance

Interventions

ledipasvir; Sofosbuvir; ledipasvir, sofosbuvir drug combination; Ribavirin

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides; Ribonucleosides; Nucleosides

Study Officials

• Francesco Negro, MD

  University Hospitals of Geneva

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 30, 2016
• First Posted: May 3, 2016
• Study Start: March 1, 2016
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2018
• Last Updated: May 1, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will share

Locations

CH (1)