Study of Cerebral Function in Patients With Chronic Hepatitis C Infection (HCV/CNS)
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| ClinicalTrials.gov Identifier: NCT00788918 |
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Recruitment Status :
Completed
First Posted : November 11, 2008
Last Update Posted : January 11, 2013
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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 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 |
| Arm | Intervention/treatment |
|---|---|
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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.
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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) |
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No Intervention: Healthy Controls
50 age, sex and education matched controls (matched 1:1 to participants in the HCV patient groups (+/- treatment)
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No Intervention: Former HCV infected
20 Subjects with prior HCV infection identified through positive HCV antibodies, but negative HCV RNA.
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No Intervention: Chronic HCV patient - no treatment
20 chronic HCV patients without pending antiviral treatment.
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- 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.
- Interferon-induced depression [ Time Frame: 8-12 weeks after treatment inititation ]
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| Ages Eligible for Study: | 18 Years to 60 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00788918
| Denmark | |
| Department of Infectious Diseases, Aarhus University Hospital, Skejby | |
| Aarhus, Jylland, Denmark, 8200 | |
| Principal Investigator: | Peter Leutscher, MD, PhD | Aarhus University Hospital, Dept. Infectious Diseases |
Additional Information:
Publications:
| 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 Key Record Dates |
| Last Update Posted: | January 11, 2013 |
| Last Verified: | January 2013 |
Keywords provided by University of Aarhus ( Aarhus University Hospital ):
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Chronic Hepatitis C cognitive dysfunction MRI MR spectroscopy |
interferon ribavirin sustained virologic response, major depressive disorder |
Additional relevant MeSH terms:
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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 |