- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00788918
Study of Cerebral Function in Patients With Chronic Hepatitis C Infection (HCV/CNS)
Study of Cerebral Function in Patients With Chronic Hepatitis C Infection Before and After Pegylated Interferon Alfa-2a and Ribavirin Therapy
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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Jylland
-
Aarhus, Jylland, Denmark, 8200
- Department of Infectious Diseases, Aarhus University Hospital, Skejby
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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.
|
Interferon 180 microgram weekly s.c. and ribavirin (800/100/1200 mg daily) p.o.
Other Names:
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
8 weeks before starting IFN+RIB therapy
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Interferon-induced depression
Time Frame: 8-12 weeks after treatment inititation
|
8-12 weeks after treatment inititation
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Peter Leutscher, MD, PhD, Aarhus University Hospital, Dept. Infectious Diseases
Publications and helpful links
General Publications
- 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.
- 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. doi: 10.1002/hep.20635.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Behavioral Symptoms
- Mental Disorders
- Digestive System Diseases
- Pathologic Processes
- Central Nervous System Diseases
- Nervous System Diseases
- RNA Virus Infections
- Virus Diseases
- Infections
- Mood Disorders
- Blood-Borne Infections
- Communicable Diseases
- Neurocognitive Disorders
- Liver Diseases
- Musculoskeletal Diseases
- Muscular Diseases
- Neuromuscular Diseases
- Flaviviridae Infections
- Hepatitis, Viral, Human
- Enterovirus Infections
- Picornaviridae Infections
- Encephalomyelitis
- Depression
- Depressive Disorder
- Disease
- Hepatitis
- Hepatitis A
- Hepatitis C
- Hepatitis, Chronic
- Hepatitis C, Chronic
- Depressive Disorder, Major
- Cognition Disorders
- Fatigue Syndrome, Chronic
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Antimetabolites
- Antineoplastic Agents
- Interferons
- Ribavirin
Other Study ID Numbers
- SKS-0078-HCVCNS
- EudraCT 2007-005707-18
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Hepatitis C, Chronic
-
Sohag UniversityRecruiting
-
Tripep ABInovio PharmaceuticalsUnknownChronic Hepatitis C Virus InfectionSweden
-
AbbVieCompletedHepatitis C Virus | Chronic Hepatitis C Virus
-
AbbVie (prior sponsor, Abbott)CompletedHepatitis C | Chronic Hepatitis C Infection | HCV | Hepatitis C Genotype 1United States
-
Humanity and Health Research CentreBeijing 302 Hospital; Nanfang Hospital of Southern Medical University; Yamanashi...Recruiting
-
Sunshine Lake Pharma Co., Ltd.CompletedChronic Hepatitis cChina
-
Ascletis Pharmaceuticals Co., Ltd.CompletedChronic Hepatitis cChina
-
Hospices Civils de LyonCompleted
-
Hadassah Medical OrganizationXTL BiopharmaceuticalsWithdrawnChronic Hepatitis C Virus InfectionIsrael
Clinical Trials on Interferon and ribavirin
-
Kaohsiung Medical University Chung-Ho Memorial...Completed
-
Minneapolis Veterans Affairs Medical CenterUS Department of Veterans Affairs; Kadmon Corporation, LLC; InterMune; San Diego... and other collaboratorsCompletedChronic Hepatitis C
-
Kaohsiung Medical University Chung-Ho Memorial...Completed
-
Kaohsiung Medical University Chung-Ho Memorial...CompletedChronic Hepatitis C | GenotypeTaiwan
-
The First Hospital of Jilin UniversityChinese Academy of SciencesUnknown
-
InterMuneCompletedChronic Hepatitis CUnited States
-
UPECLIN HC FM Botucatu UnespCompletedHepatitis, Viral, Non-A, Non-B, Parenterally-TransmittedBrazil
-
Beth Israel Medical CenterInterMuneCompleted
-
Karolinska InstitutetThe Swedish Research Council; Hoffmann-La RocheCompletedChronic Hepatitis C | Human Immunodeficiency VirusSweden
-
Sociedad Andaluza de Enfermedades InfecciosasCompletedHIV Infections | Hepatitis C, ChronicSpain