Study of Cerebral Function in Patients With Chronic Hepatitis C Infection (HCV/CNS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Aarhus ( Aarhus University Hospital )
ClinicalTrials.gov Identifier:
NCT00788918
First received: November 10, 2008
Last updated: January 10, 2013
Last verified: January 2013

November 10, 2008
January 10, 2013
November 2008
November 2012   (final data collection date for primary outcome measure)
Neuropsychological test results, cytokine profile and MRI findings [ Time Frame: 8 weeks before starting IFN+RIB therapy ] [ Designated as safety issue: No ]
Assessment performed before starting antiviral treatment in patients with chronic hepatitis C who awaits treatment. HCV patients without pending treatment will be tested in conjunction with their outpatient controls.
Pre- and posttreatment neuropsychological (cognitive) test performance. [ Time Frame: 24/48 weeks Rx plus 24 weeks follow-up ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00788918 on ClinicalTrials.gov Archive Site
Interferon-induced depression [ Time Frame: 8-12 weeks after treatment inititation ] [ Designated as safety issue: No ]
Pre and post treatment cerebral MRI and MR spectroscopic examination. [ Time Frame: 24/48 weeks Rx plus 24 weeks follow-up ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Study of Cerebral Function in Patients With Chronic Hepatitis C Infection (HCV/CNS)
Study of Cerebral Function in Patients With Chronic Hepatitis C Infection Before and After Pegylated Interferon Alfa-2a and Ribavirin Therapy

Patients with HCV infection often suffer from chronic fatigue, depression and reduced cognition, even before evolving severe liver fibrosis, liver cirrhosis and hepatic encephalopathy.

It is currently unclear to what extent the symptoms er due to a direct pathological effects of the virus itself, or due to pre-existing psychiatric disease. There is a complex relationship between prior or existing drug abuse, psychiatric disease and HCV infection, that makes it difficult to establish cause-effect relationships.

A biological mechanism has been suggested to contribute to development of cerebral dysfunction in the patients. According to the prevailing Trojan Horses hypothesis circulating lymphocytes cross the blood brain barrier carrying HCV to the central nervous system and virus is subsequently replicated in the macrophages and the microglia in brain as a separate compartment. As part of the immunological response to viral replication, neurodegenerative processes takes place with a harmful effect on the neural circuit and cerebral function. Identification of HCV RNA negative strand, a replication product, in brain tissue from HCV patients, as part of autopsy studies, supports the hypothesis. Moreover, HCV patients have also been observed with abnormal metabolic concentrations in the frontal white substance and the basal ganglia by MRI spectroscopy compared to control groups.

The overall study objective is to assess cerebral function with particular emphasis on cognitive functions in HCV patients (genotypes 1,2,3 and 4) by use of a neuropsychiatric test battery. Furthermore, the patients will be examined by MRI, including magnetization transfer, diffusion tensor and contrast perfusion, in order to perform measurements of cerebral volumetric and microstructure. Finally, HCV analysis, including viral sequences and cytokine profiles, in serum and cerebrospinal fluid will be carried out in the study population.

Not Provided
Interventional
Not Provided
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
  • Hepatitis C, Chronic
  • Cognition Disorders
  • Fatigue Syndrome, Chronic
  • Major Depressive Disorder
Drug: Interferon and ribavirin
Interferon 180 microgram weekly s.c. and ribavirin (800/100/1200 mg daily) p.o.
Other Name: Pegasys (ATC Code: L03AB11) and Copegus (ATC Code: J05AB04)
  • Experimental: Chronic hepatitis C treatment
    30 Chronic HCV patients with pending antiviral treatment. A majority will have pending treatment with interferon and ribavirin, and the treated patients will be assessed 8-12 weeks after starting treatment for interferon-induced depression.
    Intervention: Drug: Interferon and ribavirin
  • No Intervention: Healthy Controls
    50 age, sex and education matched controls (matched 1:1 to participants in the HCV patient groups (+/- treatment)
  • No Intervention: Former HCV infected
    20 Subjects with prior HCV infection identified through positive HCV antibodies, but negative HCV RNA.
  • No Intervention: Chronic HCV patient - no treatment
    20 chronic HCV patients without pending antiviral treatment.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
100
November 2012
November 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Chronic HCV infection with genotype 1, 2, 3 or 4.
  • Age > 18 and <60
  • Liver biopsy or fibroscan performed within last 5 years
  • Signed informed consent form.

Exclusion Criteria:

  • Liver biopsy showing liver pathology not due to HCV infection.
  • Liver cirrhosis or severe liver fibrosis
  • Former antiviral HCV treatment (for included HCV patients).
  • HIV and/or Hepatitis B virus infection.
  • Alcohol or drug abuse within the last 2 years.
  • Neutropenia, anemia or thrombocytopenia.
  • Clinical signs of non-compensated liver pathology.
  • Moderate to severe cardiopulmonary disease (NYHA score 1 or above)
  • Creatinine clearance < 80mL/min.
  • Pregnancy.
  • Ferromagnetic implants
  • Significant somatic disease affecting the central nervous system (somatic/neurologic disease)
  • Head trauma resulting in unconsciousness > 5min
  • Schizophrenia or other psychotic disorders
Both
18 Years to 60 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Denmark
 
NCT00788918
SKS-0078-HCVCNS, EudraCT 2007-005707-18
Yes
University of Aarhus ( Aarhus University Hospital )
Aarhus University Hospital
Not Provided
Principal Investigator: Peter Leutscher, MD, PhD Aarhus University Hospital, Dept. Infectious Diseases
University of Aarhus
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP