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

Tracking Information
First Submitted Date ICMJE	November 10, 2008
First Posted Date ICMJE	November 11, 2008
Last Update Posted Date	January 11, 2013
Study Start Date ICMJE	November 2008
Actual Primary Completion Date	November 2012 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: December 19, 2011)	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.
Original Primary Outcome Measures ICMJE; (submitted: November 10, 2008)	Pre- and posttreatment neuropsychological (cognitive) test performance. [ Time Frame: 24/48 weeks Rx plus 24 weeks follow-up ]
Change History	Complete list of historical versions of study NCT00788918 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: December 19, 2011)	Interferon-induced depression [ Time Frame: 8-12 weeks after treatment inititation ]
Original Secondary Outcome Measures ICMJE; (submitted: November 10, 2008)	Pre and post treatment cerebral MRI and MR spectroscopic examination. [ Time Frame: 24/48 weeks Rx plus 24 weeks follow-up ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Study of Cerebral Function in Patients With Chronic Hepatitis C Infection (HCV/CNS)
Official Title ICMJE	Study of Cerebral Function in Patients With Chronic Hepatitis C Infection Before and After Pegylated Interferon Alfa-2a and Ribavirin Therapy
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 Provided
Study Type ICMJE	Interventional
Study Phase	Not Applicable
Study Design ICMJE	Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label)
Condition ICMJE	Hepatitis C, Chronic; Cognition Disorders; Fatigue Syndrome, Chronic; Major Depressive Disorder
Intervention ICMJE	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)
Study Arms	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. Intervention: Drug: Interferon and ribavirin; 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.
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.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: December 6, 2012)	100
Original Estimated Enrollment ICMJE; (submitted: November 10, 2008)	120
Actual Study Completion Date	November 2012
Actual Primary Completion Date	November 2012 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 60 Years (Adult)
Accepts Healthy Volunteers	Yes
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Denmark
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00788918
Other Study ID Numbers ICMJE	SKS-0078-HCVCNS; EudraCT 2007-005707-18
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	University of Aarhus ( Aarhus University Hospital )
Study Sponsor ICMJE	Aarhus University Hospital
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Peter Leutscher, MD, PhD Aarhus University Hospital, Dept. Infectious Diseases
PRS Account	University of Aarhus
Verification Date	January 2013
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP