Chronic HCV InfectionNCT00842205
Role of Heme Oxygenase in the Pathogenesis of Hepatocellular Injury in Chronic Hepatitis C Virus (HCV) Infection
A study testing pegylated interferon and Ribavarin in people with Chronic HCV Infection and Nonalcoholic Steatohepatitis, run by Charles University, Czech Republic at 1 site in Czechia.
Trial summary
In the presented project, the role of heme oxygenase 1 and 2 in the procesess associated with fibroproduction in the chronic HCV infection will be studied. Heme oxygenase expression will be evaluated by the techniques of molecular genetics and immunohistochemistry, both in the liver tissue and in peripheral blood… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Chronic HCV Infection, Nonalcoholic Steatohepatitis
- What is being tested?
- pegylated interferon and Ribavarin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteCzechia
- Study dates
- Jan 2007to Dec 2009
- 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
- No healthy volunteers
- Adult
Who may be able to join
- chronic HCV infection
- must undergo liver biopsy
- must undergo antiviral treatment
Who cannot join
- liver sample not obtained
- blood samples for HCV testing not obtained in specified time points during antiviral therapy
Trial locations and contacts
1 site in 1 country.
Czechia1 site, 1 recruiting
- Recruiting
Cetral Military Hospital
Prague, 16202
Petr Urbanek, Doc., MD, CSc, +420973203049, petr.urbanek@uvn.cz
Petr Urbanek, Doc., MD, CSc
About this study
Official title: Role of Heme Oxygenase in the Pathogenesis od Hepatocellular Injury in Chronic HCV Infection
In the presented project, the role of heme oxygenase 1 and 2 in the procesess associated with fibroproduction in the chronic HCV infection will be studied. Heme oxygenase expression will be evaluated by the techniques of molecular genetics and immunohistochemistry, both in the liver tissue and in peripheral blood mononuclear cells. These parameters will be correlated with basic virological and clinical characteristics of the chronic HCV infection. The investigators' expected results may help in understanding the mechanisms of fibroproduction in chronic HVC infection and, therefore, contribute to explain individual differences in the development of chronic HCV infection.
Read the detailed description
Hepatitis C virus (HCV) is a single stranded positive RNA virus belonging to the Flaviviridae family. HCV is a major cause of chronic hepatitis and progressive liver fibrosis leading to cirrhosis. Currently, the mechanisms responsible for hepatocellular injury are not fully understood. Oxidative damage has been hypothesized to play a role in HCV-induced liver disease, with reactive oxygen species (ROS), generated from HCV-infected hepatocytes and infiltrating immune cells. Persistence of recurrent hepatocellular injury leads to wound-healing process in which oxidative stress, inflammatory response mediated by immune cells and/or cytokines, and activation of hepatic stellate cells (HSCs) contribute to cascade of fibrogenesis. HCV can infect peripheral blood mononuclear cells (PBMC) of patients with chronic HCV infection . PBMC play key roles both in innate and adaptive antigen-specific immunity and they constitute critical components of the immune response.Heme oxygenase (HO) is the rate-limiting enzyme in the heme catabolic pathway. It cleaves pro-oxidant heme into equimolar amounts of carbon monoxide (CO), free iron, and biliverdin, which is rapidly metabolized to bilirubin by biliverdin reductase.The human HO-1 gene is located at chromosome 22q12 and a variable number of tandem repeat polymorphism (VNTR) was identified in the proximal promoter region. It is suggested that these highly polymorphic (GT)n repeats could alter the transcriptional activity. In recent years, enhanced HO enzymatic activity has been reported - probably through its formation of bioactive products - to possess antioxidant, cytoprotective, and neurotransmitter activity and to play a role in anti-inflammatory functions . AIMS: AIM 1.To characterize HO expression in liver biopsies in patients with chronic hepatitis C comparing to expression in patients with other types of hepatitis (esp. autoimmune) and to normal liver tissue. To investigate the relationship between HO expression and hepatitis C virus concentration, duration of infection, level of fibrosis and inflammation, ALT, AST activities, bilirubin levels, response to the standard treatment and a level of apoptosis. AIM 2. To characterize HO expression in PBMC in patients with chronic hepatitis C before, in the week 12 and after the standard treatment (PEG-IFN+RBV). To correlate HO expression in PBMC with viral concentration in sera and a response to the standard treatment.AIM 3. To investigate HO polymorphisms in patients with chronic hepatitis C. AIM 4. To investigate UGT1A1 28 polymorphism which is responsible for benign hyperbilirubinemia. Expected results: 1. This study could elucidate a relationship between development of liver fibrosis and inflammation and HO expression. 2. This project may, for the first time, show the relationship between chronic HCV infection and regulation of HO expression in PBMC. 3.This project will answer the question whether genetic predisposition, length polymorphism in HO promoter responsible for its lower transcriptional activity, could be a risk factor for fibrosis/cirrhosis development in patients infected with hepatitis C virus. UGT1A1 28 polymorphism is connected with low prevalence of diseases in which the oxidative stress is increased. We suggest that HCV infected persons might have low prevalence of this polymorphism or this polymorphism might be connected to low efficacy of antiviral treatment in these persons.
- Being tested
- pegylated interferon, Ribavarin
- Keywords
- hepatitis C, NASH, Hem Oxygenase, Gene polymorphism
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pegylated interferonDrug
Also called Pegasys, Pegintron
peg-IFN alfa 2a 180ug s.c. QW or peg-IFN alfa 2b 1.5 ug/kg s.c. QW
RibavarinDrug
Also called Copegus, Rebetol
ribavirin 1000-1200mg p.o. daily 48weeks or ribavirin 100-1200mg p.o. daily 48 weeks
| Study group | Role | What they receive |
|---|---|---|
| 1 HCV positive pts | Active comparator | Patients with chronic HCV infection undergoing liver biopsy followed by antiviral treatment.
peg-IFN alfa 2a 180ug s.c. QW + ribavirin 1000-1200mg p.o. daily 48weeks or peg-IFN alfa 2b 1.5 ug/kg s.c. QW + ribavirin 100-1200mg p.o. daily 48 weeks Receives: Drug: pegylated interferon; Drug: Ribavarin |
| 2 Other liver disease | No intervention | pts. with NASH (or other liver disease) undergoing liver biopsy. |
What is being measured
The primary outcome is the main question the study is designed to answer.
1. the relation between HO activity and basic virologic and histologic parameters in chronic HCV patients. 2. changes of HO activity within antiviral treatment 3. relation of HO gene polymorphisms to the course of disease
Measured: from HCV transmission in each individual patient to the time of liver biopsy and begining of antiviral treatment
Secondary outcomes (1)
Relation of HO gene polymorphisms and UGT1A1*28 polymorphism.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2009 (estimated)
- Study startJan 2007
- Primary completionJun 2009 (estimated)
- Study completionDec 2009 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic HCV InfectionStudies of the same condition, open and under way.
- More trials run by Charles University, Czech RepublicThe 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
- Primary purpose
- Basic science
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Charles University, Czech Republic
- Sponsor type
- University, hospital or other
- Collaborators
- IGA MZ, Czech Republic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00842205
- Sponsor's protocol ID
- IGA MZ CR NR9412-3
- Status last verified
- Feb 2009
- First submitted
- 11 Feb 2009
- Last updated
- 12 Feb 2009
- Results posted
- No
- Data monitoring committee
- No
Publications
Urbanek P, Lenicek M, Muchova L, Subhanova I, Dusek L, Kasprikova N, Hrabal P, Bruha R, Vitek L. No association of promoter variations of HMOX1 and UGT1A1 genes with liver injury in chronic hepatitis C. Ann Hepatol. 2011 Oct-Dec;10(4):445-51.
PubMed 21911884
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Heme Oxygenase in the Pathogenesis od Hepatocellular Injury in Chronic HCV Infection
- ClinicalTrials.gov ID
- NCT00842205
- Acronym / sponsor ID
- IGA MZ CR NR9412-3
- Keywords
- hepatitis C, NASH, Hem Oxygenase, Gene polymorphism
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Charles University, Czech RepublicUniversity, hospital or other
- Collaborators
- IGA MZ, Czech Republic
- Study start
- Jan 2007
- Primary completion
- Jun 2009 (estimated)
- Study completion
- Dec 2009 (estimated)
- First posted
- 12 Feb 2009 (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.
In the presented project, the role of heme oxygenase 1 and 2 in the procesess associated with fibroproduction in the chronic HCV infection will be studied. Heme oxygenase expression will be evaluated by the techniques of molecular genetics and immunohistochemistry, both in the liver tissue and in peripheral blood mononuclear cells. These parameters will be correlated with basic virological and clinical characteristics of the chronic HCV infection. The investigators' expected results may help in understanding the mechanisms of fibroproduction in chronic HVC infection and, therefore, contribute to explain individual differences in the development of chronic HCV infection.
Detailed description
Hepatitis C virus (HCV) is a single stranded positive RNA virus belonging to the Flaviviridae family. HCV is a major cause of chronic hepatitis and progressive liver fibrosis leading to cirrhosis. Currently, the mechanisms responsible for hepatocellular injury are not fully understood. Oxidative damage has been hypothesized to play a role in HCV-induced liver disease, with reactive oxygen species (ROS), generated from HCV-infected hepatocytes and infiltrating immune cells. Persistence of recurrent hepatocellular injury leads to wound-healing process in which oxidative stress, inflammatory response mediated by immune cells and/or cytokines, and activation of hepatic stellate cells (HSCs) contribute to cascade of fibrogenesis. HCV can infect peripheral blood mononuclear cells (PBMC) of patients with chronic HCV infection . PBMC play key roles both in innate and adaptive antigen-specific immunity and they constitute critical components of the immune response.Heme oxygenase (HO) is the rate-limiting enzyme in the heme catabolic pathway. It cleaves pro-oxidant heme into equimolar amounts of carbon monoxide (CO), free iron, and biliverdin, which is rapidly metabolized to bilirubin by biliverdin reductase.The human HO-1 gene is located at chromosome 22q12 and a variable number of tandem repeat polymorphism (VNTR) was identified in the proximal promoter region. It is suggested that these highly polymorphic (GT)n repeats could alter the transcriptional activity. In recent years, enhanced HO enzymatic activity has been reported - probably through its formation of bioactive products - to possess antioxidant, cytoprotective, and neurotransmitter activity and to play a role in anti-inflammatory functions . AIMS: AIM 1.To characterize HO expression in liver biopsies in patients with chronic hepatitis C comparing to expression in patients with other types of hepatitis (esp. autoimmune) and to normal liver tissue. To investigate the relationship between HO expression and hepatitis C virus concentration, duration of infection, level of fibrosis and inflammation, ALT, AST activities, bilirubin levels, response to the standard treatment and a level of apoptosis. AIM 2. To characterize HO expression in PBMC in patients with chronic hepatitis C before, in the week 12 and after the standard treatment (PEG-IFN+RBV). To correlate HO expression in PBMC with viral concentration in sera and a response to the standard treatment.AIM 3. To investigate HO polymorphisms in patients with chronic hepatitis C. AIM 4. To investigate UGT1A1 28 polymorphism which is responsible for benign hyperbilirubinemia. Expected results: 1. This study could elucidate a relationship between development of liver fibrosis and inflammation and HO expression. 2. This project may, for the first time, show the relationship between chronic HCV infection and regulation of HO expression in PBMC. 3.This project will answer the question whether genetic predisposition, length polymorphism in HO promoter responsible for its lower transcriptional activity, could be a risk factor for fibrosis/cirrhosis development in patients infected with hepatitis C virus. UGT1A1 28 polymorphism is connected with low prevalence of diseases in which the oxidative stress is increased. We suggest that HCV infected persons might have low prevalence of this polymorphism or this polymorphism might be connected to low efficacy of antiviral treatment in these persons.
Study design
- Primary purpose
- Basic science
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 HCV positive pts | Active comparator | Drug: pegylated interferon, Drug: RibavarinPatients with chronic HCV infection undergoing liver biopsy followed by antiviral treatment. peg-IFN alfa 2a 180ug s.c. QW + ribavirin 1000-1200mg p.o. daily 48weeks or peg-IFN alfa 2b 1.5 ug/kg s.c. QW + ribavirin 100-1200mg p.o. daily 48 weeks |
| 2 Other liver disease | No intervention | –pts. with NASH (or other liver disease) undergoing liver biopsy. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- chronic HCV infection
- must undergo liver biopsy
- must undergo antiviral treatment
Key exclusion criteria (2 listed)
- liver sample not obtained
- blood samples for HCV testing not obtained in specified time points during antiviral therapy
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 |
|---|---|---|
| pegylated interferonAlso: Pegasys, Pegintronpeg-IFN alfa 2a 180ug s.c. QW or peg-IFN alfa 2b 1.5 ug/kg s.c. QW | Drug | 1 HCV positive pts |
| RibavarinAlso: Copegus, Rebetolribavirin 1000-1200mg p.o. daily 48weeks or ribavirin 100-1200mg p.o. daily 48 weeks | Drug | 1 HCV positive pts |
Primary outcome
1. the relation between HO activity and basic virologic and histologic parameters in chronic HCV patients. 2. changes of HO activity within antiviral treatment 3. relation of HO gene polymorphisms to the course of disease
Time frame: from HCV transmission in each individual patient to the time of liver biopsy and begining of antiviral treatment
1 secondary outcome
Relation of HO gene polymorphisms and UGT1A1*28 polymorphism.
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2009.
- Derived from this study: PubMed 21911884Urbanek P, Lenicek M, Muchova L, Subhanova I, Dusek L, Kasprikova N, Hrabal P, Bruha R, Vitek L. No association of promoter variations of HMOX1 and UGT1A1 genes with liver injury in chronic hepatitis C. Ann Hepatol. 2011 Oct-Dec;10(4):445-51.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing pegylated interferon and Ribavarin in people with Chronic HCV Infection and Nonalcoholic Steatohepatitis, run by Charles University, Czech Republic at 1 site in Czechia.
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 3 inclusion and 2 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: status not confirmed, as of the sponsor's last update on 12 Feb 2009. 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 Czechia. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
1. the relation between HO activity and basic virologic and histologic parameters in chronic HCV patients. 2. changes of HO activity within antiviral treatment 3. relation of HO gene polymorphisms to the course of disease (time frame: from HCV transmission in each individual patient to the time of liver biopsy and begining of antiviral treatment). 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 NCT00842205, which also lists 1 linked publication.
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 12 Feb 2009.