Clinical trial NCT00788918: Study of Cerebral Function in Patients With Chronic Hepatitis C Infection (HCV/CNS)
Official title: Study of Cerebral Function in Patients With Chronic Hepatitis C Infection Before and After Pegylated Interferon Alfa-2a and Ribavirin Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hepatitis C, Chronic
Cognition Disorders
Fatigue Syndrome, Chronic
Major Depressive Disorder
Keywords: Chronic Hepatitis C
cognitive dysfunction
MRI
MR spectroscopy
interferon
ribavirin
sustained virologic response, major depressive disorder
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2008-11-11
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP

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.


Eligibility 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

Primary outcomes:
measure: Neuropsychological test results, cytokine profile and MRI findings
timeFrame: 8 weeks before starting IFN+RIB therapy
Secondary outcomes:
measure: Interferon-induced depression
timeFrame: 8-12 weeks after treatment inititation
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Department of Infectious Diseases, Aarhus University Hospital, Skejby
state: Jylland
Study officials:
affiliation: Aarhus University Hospital, Dept. Infectious Diseases
name: Peter Leutscher, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Perry W, Hilsabeck RC, Hassanein TI. Cognitive dysfunction in chronic hepatitis C: a review. Dig Dis Sci. 2008 Feb;53(2):307-21. doi: 10.1007/s10620-007-9896-z. Epub 2007 Aug 17.
citation: 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.
citation: 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. doi: 10.1002/hep.20635.
citation: 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. doi: 10.1016/j.genhosppsych.2005.06.006.
citation: 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. doi: 10.1097/01.aids.0000192083.41561.00.