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

Not Applicable

Completed

• Conditions: Cognition Disorders; Fatigue Syndrome, Chronic; Hepatitis C, Chronic; Major Depressive Disorder
• Interventions: Drug: Interferon and ribavirin

• Registration Number: NCT00788918
• Lead Sponsor: Aarhus University Hospital

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2008-11
• Study First Submitted: 2008-11-10
• Study First Submitted QC: 2008-11-10
• Study First Posted: 2008-11-11
• Primary Completion: 2012-11
• Study Completion: 2012-11
• Status Verified: 2013-01
• Last Update Submitted: 2013-01-10
• Last Update Posted: 2013-01-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 100

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Chronic hepatitis C treatment	Interferon and ribavirin	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.

Primary Outcome Measures

Name	Time	Method
Neuropsychological test results, cytokine profile and MRI findings	8 weeks before starting IFN+RIB therapy	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

Name	Time	Method
Interferon-induced depression	8-12 weeks after treatment inititation

Trial Locations

Locations (1)

Department of Infectious Diseases, Aarhus University Hospital, Skejby; 🇩🇰 Aarhus, Jylland, Denmark