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
  Purpose

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.


Condition Intervention
Hepatitis C, Chronic
Cognition Disorders
Fatigue Syndrome, Chronic
Major Depressive Disorder
Drug: Interferon and ribavirin

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Study of Cerebral Function in Patients With Chronic Hepatitis C Infection Before and After Pegylated Interferon Alfa-2a and Ribavirin Therapy

Resource links provided by NLM:


Further study details as provided by University of Aarhus:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • Interferon-induced depression [ Time Frame: 8-12 weeks after treatment inititation ] [ Designated as safety issue: No ]

Enrollment: 100
Study Start Date: November 2008
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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)
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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00788918

Locations
Denmark
Department of Infectious Diseases, Aarhus University Hospital, Skejby
Aarhus, Jylland, Denmark, 8200
Sponsors and Collaborators
Aarhus University Hospital
Investigators
Principal Investigator: Peter Leutscher, MD, PhD Aarhus University Hospital, Dept. Infectious Diseases
  More Information

Additional Information:
Publications:
Responsible Party: University of Aarhus ( Aarhus University Hospital )
ClinicalTrials.gov Identifier: NCT00788918     History of Changes
Other Study ID Numbers: SKS-0078-HCVCNS, EudraCT 2007-005707-18
Study First Received: November 10, 2008
Last Updated: January 10, 2013
Health Authority: Denmark: The Regional Committee on Biomedical Research Ethics
Denmark: Danish Dataprotection Agency

Keywords provided by University of Aarhus:
Chronic Hepatitis C
cognitive dysfunction
MRI
MR spectroscopy
interferon
ribavirin
sustained virologic response, major depressive disorder

Additional relevant MeSH terms:
Hepatitis C, Chronic
Cognition Disorders
Depressive Disorder
Depression
Fatigue
Fatigue Syndrome, Chronic
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Depressive Disorder, Major
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Mood Disorders
Behavioral Symptoms
Signs and Symptoms
Virus Diseases
Muscular Diseases
Musculoskeletal Diseases
Encephalomyelitis
Central Nervous System Diseases
Nervous System Diseases
Neuromuscular Diseases
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections

ClinicalTrials.gov processed this record on July 22, 2014