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

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Condition or disease	Intervention/treatment	Phase
Hepatitis C, Chronic; Cognition Disorders; Fatigue Syndrome, Chronic; Major Depressive Disorder	Drug: Interferon and ribavirin	Not Applicable

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	100 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (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
Study Start Date :	November 2008
Actual Primary Completion Date :	November 2012
Actual Study Completion Date :	November 2012

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
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.

Outcome Measures

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Primary Outcome Measures :

1. Neuropsychological test results, cytokine profile and MRI findings [ Time Frame: 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 :

1. Interferon-induced depression [ Time Frame: 8-12 weeks after treatment inititation ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 60 Years (Adult)
Sexes Eligible for Study:	All
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

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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

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Additional Information:

Center for Functionally Integrative Neuroscience, Aarhus University Hospital 

Center for Psychiatric Research, Aarhus University Hospital 

Publications:

Perry W, Hilsabeck RC, Hassanein TI. Cognitive dysfunction in chronic hepatitis C: a review. Dig Dis Sci. 2008 Feb;53(2):307-21. Epub 2007 Aug 17. Review.

Forton DM, Hamilton G, Allsop JM, Grover VP, Wesnes K, O'Sullivan C, Thomas HC, Taylor-Robinson SD. Cerebral immune activation in chronic hepatitis C infection: a magnetic resonance spectroscopy study. J Hepatol. 2008 Sep;49(3):316-22. doi: 10.1016/j.jhep.2008.03.022. Epub 2008 Apr 25.

McAndrews MP, Farcnik K, Carlen P, Damyanovich A, Mrkonjic M, Jones S, Heathcote EJ. Prevalence and significance of neurocognitive dysfunction in hepatitis C in the absence of correlated risk factors. Hepatology. 2005 Apr;41(4):801-8.

Golden J, O'Dwyer AM, Conroy RM. Depression and anxiety in patients with hepatitis C: prevalence, detection rates and risk factors. Gen Hosp Psychiatry. 2005 Nov-Dec;27(6):431-8.

Laskus T, Radkowski M, Adair DM, Wilkinson J, Scheck AC, Rakela J. Emerging evidence of hepatitis C virus neuroinvasion. AIDS. 2005 Oct;19 Suppl 3:S140-4. Review.

Responsible Party:	Aarhus University Hospital
ClinicalTrials.gov Identifier:	NCT00788918 History of Changes
Other Study ID Numbers:	SKS-0078-HCVCNS; EudraCT 2007-005707-18
First Posted:	November 11, 2008
Last Update Posted:	January 11, 2013
Last Verified:	January 2013

Keywords provided by University of Aarhus ( Aarhus University Hospital ):

Chronic Hepatitis C; cognitive dysfunction; MRI; MR spectroscopy	interferon; ribavirin; sustained virologic response, major depressive disorder

Additional relevant MeSH terms:

Disease; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis, Chronic; Depressive Disorder; Depression; Depressive Disorder, Major; Fatigue; Hepatitis C, Chronic; Cognition Disorders; Fatigue Syndrome, Chronic; Pathologic Processes; Liver Diseases; Digestive System Diseases	Hepatitis, Viral, Human; Virus Diseases; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Flaviviridae Infections; Mood Disorders; Mental Disorders; Behavioral Symptoms; Signs and Symptoms; Neurocognitive Disorders; Muscular Diseases; Musculoskeletal Diseases; Encephalomyelitis; Central Nervous System Diseases