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
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Hepatitis C virus-induced insulin resistance
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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
干预措施: Ledipasvir 90 mg/Sofosbuvir 400 mg (Drug)
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
干预措施: Ribavirin (Drug)
结局指标
主要结局
Hepatitis C virus-induced insulin resistance
时间窗: 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.
次要结局
未报告次要终点
研究者
Negro Francesco
Professor
University Hospital, Geneva