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

Major Depressive Disorder Clinical Trial

Official title:

Study of Cerebral Function in Patients With Chronic Hepatitis C Infection Before and After Pegylated Interferon Alfa-2a and Ribavirin Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00788918
• Other study ID #: SKS-0078-HCVCNS
• Secondary ID: EudraCT 2007-005
• Status: Completed
• Phase: N/A
• First received: November 10, 2008
• Last updated: January 10, 2013
• Start date: November 2008
• Est. completion date: November 2012

Study information

• Verified date: January 2013
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: The Regional Committee on Biomedical Research EthicsDenmark: Danish Dataprotection Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Cognition Disorders
• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Disease
• Fatigue Syndrome, Chronic
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic
• Major Depressive Disorder

Intervention

Drug:
• Interferon and ribavirin
Interferon 180 microgram weekly s.c. and ribavirin (800/100/1200 mg daily) p.o.

Locations

Country	Name	City	State
Denmark	Department of Infectious Diseases, Aarhus University Hospital, Skejby	Aarhus	Jylland

Sponsors (1)

Lead Sponsor	Collaborator
Aarhus University Hospital

Country where clinical trial is conducted

Denmark, 

References & Publications (5)

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. — View 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. — View 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. Review. — View 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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neuropsychological test results, cytokine profile and MRI findings	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.	8 weeks before starting IFN+RIB therapy	No
Secondary	Interferon-induced depression		8-12 weeks after treatment inititation	No

External Links

•   Center for Functionally Integrative Neuroscience, Aarhus University Hospital
•   Center for Psychiatric Research, Aarhus University Hospital