Hepatitis C, ChronicNCT00788918
Study of Cerebral Function in Patients With Chronic Hepatitis C Infection (HCV/CNS)
A study testing Interferon and ribavirin in people with Hepatitis C, Chronic and Cognition Disorders, run by Aarhus University Hospital at 1 site in Denmark.
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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatitis C, Chronic, Cognition Disorders, Fatigue Syndrome, Chronic
- What is being tested?
- Interferon and ribavirin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteDenmark
- Study dates
- Nov 2008to Nov 2012
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Department of Infectious Diseases, Aarhus University Hospital, Skejby
Aarhus, Jylland, 8200
About this study
Official title: 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.
Read more
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.
- Conditions
- Hepatitis C, Chronic, Cognition Disorders, Fatigue Syndrome, Chronic, Major Depressive Disorder
- Being tested
- Interferon and ribavirin
- Keywords
- Chronic Hepatitis C, cognitive dysfunction, MRI, MR spectroscopy, interferon, ribavirin, sustained virologic response, major depressive disorder
- Medical subject headings
- Hepatitis C, Chronic, Cognition Disorders, Fatigue Syndrome, Chronic, Depressive Disorder, Major, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Interferon and ribavirinDrug
Also called Pegasys (ATC Code: L03AB11) and Copegus (ATC Code: J05AB04)
Interferon 180 microgram weekly s.c. and ribavirin (800/100/1200 mg daily) p.o.
| Study group | Role | What they receive |
|---|---|---|
| Chronic hepatitis C treatment | Experimental | 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. Receives: Drug: Interferon and ribavirin |
| Healthy Controls | No intervention | 50 age, sex and education matched controls (matched 1:1 to participants in the HCV patient groups (+/- treatment) |
| Former HCV infected | No intervention | 20 Subjects with prior HCV infection identified through positive HCV antibodies, but negative HCV RNA. |
| Chronic HCV patient - no treatment | No intervention | 20 chronic HCV patients without pending antiviral treatment. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 8 weeks before starting IFN+RIB therapy
Secondary outcomes (1)
Interferon-induced depression
Measured: 8-12 weeks after treatment inititation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2008 (estimated)
- Study startNov 2008
- Primary completionNov 2012
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Hepatitis C, ChronicStudies of the same condition, open and under way.
- More trials run by Aarhus University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aarhus University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Peter Leutscher, MD, PhD, Principal investigator, Aarhus University Hospital, Dept. Infectious Diseases
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00788918
- Sponsor's protocol ID
- SKS-0078-HCVCNS
- Other IDs
- EudraCT 2007-005707-18
- Status last verified
- Jan 2013
- First submitted
- 10 Nov 2008
- Last updated
- 11 Jan 2013
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 17703362Forton 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.
PubMed 18538439McAndrews 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.
PubMed 15793853Golden 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.
PubMed 16271658Laskus 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.
PubMed 16251811
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Cerebral Function in Patients With Chronic Hepatitis C Infection Before and After Pegylated Interferon Alfa-2a and Ribavirin Therapy
- ClinicalTrials.gov ID
- NCT00788918
- Acronym / sponsor ID
- SKS-0078-HCVCNS
- 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
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Aarhus University HospitalUniversity, hospital or other
- Study start
- Nov 2008
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 11 Nov 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Chronic hepatitis C treatment | Experimental | Drug: Interferon and ribavirin30 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. |
| Healthy Controls | No intervention | –50 age, sex and education matched controls (matched 1:1 to participants in the HCV patient groups (+/- treatment) |
| Former HCV infected | No intervention | –20 Subjects with prior HCV infection identified through positive HCV antibodies, but negative HCV RNA. |
| Chronic HCV patient - no treatment | No intervention | –20 chronic HCV patients without pending antiviral treatment. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Interferon and ribavirinAlso: Pegasys (ATC Code: L03AB11) and Copegus (ATC Code: J05AB04)Interferon 180 microgram weekly s.c. and ribavirin (800/100/1200 mg daily) p.o. | Drug | Chronic hepatitis C treatment |
Primary outcome
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.
1 secondary outcome
Interferon-induced depression
Time frame: 8-12 weeks after treatment inititation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2013.
- Background: PubMed 17703362Perry 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.
- Background: PubMed 18538439Forton 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.
- Background: PubMed 15793853McAndrews 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.
- Background: PubMed 16271658Golden 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.
- Background: PubMed 16251811Laskus 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.
- Center for Functionally Integrative Neuroscience, Aarhus University HospitalLink provided by the sponsor.
- Center for Psychiatric Research, Aarhus University HospitalLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Leutscher, MD, PhD principal investigator
Aarhus University Hospital, Dept. Infectious Diseases
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Interferon and ribavirin in people with Hepatitis C, Chronic and Cognition Disorders, run by Aarhus University Hospital at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neuropsychological test results, cytokine profile and MRI findings (time frame: 8 weeks before starting IFN+RIB therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00788918, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2013.