We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
ClinicalTrials.gov Menu

THISTLE - The HIV-HCV Silibinin Trial (THISTLE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01816490
Recruitment Status : Completed
First Posted : March 22, 2013
Last Update Posted : March 5, 2015
Information provided by (Responsible Party):
University of Zurich

Brief Summary:

Chronic hepatitis C virus (HCV) is a major cause of morbidity and mortality worldwide with an estimated number of 180 million infected patients. Until 2012 the current standard of care (SOC) treatment of patients with chronic hepatitis C was a 24 to 72 weeks therapy with pegylated interferon- and ribavirin (PR). In 2012, the protease-inhibitors (PI's) telaprevir and boceprevir as first directly acting HCV drugs have been approved by the local Swiss authority for hepatitis C mono-infected and HCV-HIV-co-infected individuals. However, therapy success is strongly limited in null-responders (NR) to previous PR. Treatment of HCV-HIV co-infected individuals with the new PI's is accompanied by additional challenges (e.g. drug-drug interactions, toxicity, high pill burden). Patients with advanced fibrosis are at highest risk for decompensated liver disease and hepatocellular carcinoma (HCC) and prompt initiation of treatment is strongly recommended. Recently, data in mono-infected patients showed, that in prior non responders a 12 week course of a triple therapy (TT) with telaprevir and PR followed by another 24 weeks of PR resulted in an sustained virologic response (SVR) of only 29%. In HCV-HIV co-infected non-responders with unfavourable preconditions (e.g. HCV-genotype 1, interleukin 28 B non-CC genotype, advanced liver fibrosis, high baseline HCV viral load) SVR after TT is even expected to be lower. These patients urgently need additional therapeutic options with the goal to eradicate HCV in order to prevent further fibrosis progression and to reduce morbidity and mortality. A promising substance in the field of drugs targeting the HCV replication is silibinin. Silibinin is the main component of silymarin, an extract of the milk thistle Silybum marianum. Intravenous silibinin (iSIL) targets multiple steps in the virus life cycle and exhibits anti-oxidant, anti-inflammatory, anti-viral and immunomodulatory properties. iSIL inhibits the HCV NS5B polymerase activity directly or by interfering with the binding of RNA to this enzyme. In addition, iSIL appears to block virus entry, virus transmission and virus secretion.In 2008 Ferenci et al. for the first time reported the substantial clinical antiviral-effect of intravenous silibinin (iSIL) against HCV in PR non-responders. The administration of 20mg/kg iSIL in 20 patients led to a highly significant decrease in viral load. We intend to investigate the effect and tolerability of iSIL in HIV-HCV co-infected individuals with advanced liver fibrosis and previous non- or partial response to SOC. All included study-subjects will receive a lead-in therapy with iSIL in a dosage of 20mg/kg/day (expressed as silibinin concentration) once a day for 14 days. At the end of the THISTLE study, i.e. after the day of completion of the 14-day iSIL administration (day 15), the patients will be considered for eligibility to receive standard of care. We assume that the decline in HCV viral load would substantially improve the chances of SVR as the reduction of viral load should both increase the efficacy of PR and reduce the odds of drug resistance to HCV-specific protease inhibitor.

  • Trial with medicinal product

Condition or disease Intervention/treatment Phase
HIV Hepatitis C Drug: Intravenous Silibinin (iSIL) Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Multi-center, Open-label, Interventional Study to Evaluate the Safety of Intravenous Silibinin (iSIL) and Its Effect on the Hepatitis C Virus Load in Treatment-experienced HCV-HIV Co-infected Individuals With Advanced Liver Fibrosis in the Swiss HIV Cohort Study (SHCS)
Study Start Date : April 2013
Actual Primary Completion Date : April 2014
Actual Study Completion Date : December 2014

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. Frequency of adverse events during iSIL treatment. [ Time Frame: Day 15 (after 14days of treatment) ]
    The participants will be followed for the duration of study-drug administration and one day follow-up, which counts for 15days

  2. Kinetics of the decline in HCV-RNA after 2 weeks of iSIL treatment (difference in IU/ml from day 1 to day 15). [ Time Frame: Day 15 ]
    The participants will be followed for the duration of study-drug administration and one day follow-up, which counts for 15days

Secondary Outcome Measures :
  1. Drug levels of iSIL and its influence on the drug-level of co-administrated ART. [ Time Frame: Day 15 ]
    The participants will be followed for the duration of study-drug administration and one day follow-up, which counts for 15days

  2. Proportion of patients with HIV virological failure, i.e. confirmed viremia >50cp/ml. [ Time Frame: Day 15 ]
    The participants will be followed for the duration of study-drug administration and one day follow-up, which counts for 15days

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion criteria:

  • Age greater or equal 18 years
  • HIV-HCV co-infection
  • HCV Genotype 1 infection
  • At least one liver biopsy since diagnosis of HCV-infection
  • Fibrosis score METAVIR = 2 documented by biopsy OR a stiffness greater or equal 7.0 kPa documented by fibroscan during the previous 12 months.
  • Documented previous null-response or partial-response to SOC

Exclusion criteria:

  • Contraindications to the study drug under study, e.g. known hypersensitivity or allergy to any ingredient of the study drug
  • Patients in need of ART with HIV virological failure (= 400 copies/ml) in the last 3 months

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): NCT01816490

Layout table for location information
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich
Zurich, Switzerland, 8091
Sponsors and Collaborators
University of Zurich
Layout table for investigator information
Principal Investigator: Dominique Braun, MD University Hospital Zurich, Division of Infectious Diseases and
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: University of Zurich
ClinicalTrials.gov Identifier: NCT01816490    
Other Study ID Numbers: THISTLE
First Posted: March 22, 2013    Key Record Dates
Last Update Posted: March 5, 2015
Last Verified: September 2013
Additional relevant MeSH terms:
Layout table for MeSH terms
Hepatitis C
Hepatitis, Viral, Human
Liver Diseases
Digestive System Diseases
Virus Diseases
RNA Virus Infections
Blood-Borne Infections
Communicable Diseases
Flaviviridae Infections
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Protective Agents
Physiological Effects of Drugs