Hepatitis BNCT00152880
Apoptosis and Hepatitis B: The Role of Apoptosis in Patients Who Are HBeAg Negative
An observational study of Hepatitis B, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
A large number hepatitis B surface antigen positive individuals are HBeAg negative with normal liver tests. Historically, such patients were thought to have suppressed viral replication and were considered to be at low risk for complications. Read more about this study
- Who is it for?
- Ages 18 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatitis B
- How many people
- 30 participants
- Where
- 1 siteCanada
- Study dates
- Jul 2005to not given
- Phase
- Observational
- 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 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- HBsAg positive.
- Stable HBeAg status for at least one year prior to biopsy.
- Normal ALT levels (defined as <1.5 x the upper limit of normal) for at least 90 days prior to biopsy.
- HBV DNA ≥10,000 copies/mL by PCR measured within 90 days of liver biopsy.
- patients attending Liver Clinic at Toronto Western Hospital, Toronto, ON, Canada
Who cannot join
- Coinfection with viral hepatitis A, C or D.
- Coinfection with HIV.
- Presence of Hepatoma.
- Known presence of other malignancy.
- Previous antiviral treatment.
Trial locations and contacts
1 site in 1 country.
Brandusa Florica contact
Canada1 site, 1 recruiting
- Recruiting
Liver Clinic, Toronto Western Hospital, UHN.
Toronto, Ontario, M5T 2S8
Jenny (E.J.L.) Heathcote, MD, 416-603-5914
E.J.L (Jenny) Heathcote, MD
About this study
Official title: Apoptosis and Hepatitis B: The Role of Apoptosis in Patients Who Are HBeAg Negative, Have Normal ALT, and HBV DNA ≥10,000 Copies/mL
A large number hepatitis B surface antigen positive individuals are HBeAg negative with normal liver tests. Historically, such patients were thought to have suppressed viral replication and were considered to be at low risk for complications. With the use of more sensitive technology, physicians are now able to identify a group of patients who are HBeAg negative, have normal liver enzymes, and detectable HBV DNA. Some of these patients develop signs of liver inflammation and fibrosis on biopsy. We intend to investigate whether normal, programmed cell death (apoptosis) plays a role in causing the silent liver injury in this group of patients. In other words the purpose of this study is to see whether apoptosis may be responsible for the silent liver death and injury that occurs in these so called inactive carriers who are HBeAg negative, have normal serum ALT values and HBV DNA > 10,000 copies/mL. In this study the liver biopsies would be routinely collected in the clinic and investigated for the evidence of inflammation and fibrosis, and special testing would be performed to detect for evidence of apoptosis. Around 30 patients from UHN would be participating in this study. This study will test the hypothesis that subjects who are HBeAg negative, have normal ALT and have HBV DNA ≥10,000 copies/mL will demonstrate an increased rate of apoptosis in liver tissue compared to healthy age-matched controls. If this hypothesis is confirmed, it will imply that the previous assumption that this group of patients has inactive disease is false and would implicate apoptosis as an important mechanism responsible for causing liver damage. If apoptotic activity is indeed elevated, further study of these pathways could potentially yield therapeutic interventions to inhibit apoptosis.
Read the detailed description
Through a retrospective chart review, patients with HBsAg who are HBeAg negative, have normal ALT, and HBV DNA >10,000 copies/mL and who have or who are about to undergo liver biopsy will be identified. These individuals will be patients at the Toronto Western Hospital Liver Clinics. Inclusion criteria:(1) HBsAg positive.(2) Stable HBeAg status for at least one year prior to biopsy.(3) Normal ALT levels (defined as <1.5 x the upper limit of normal) for at least 90 days prior to biopsy.(4) HBV DNA ≥10,000 copies/mL by PCR measured within 90 days of liver biopsy.Exclusion criteria:(1) Coinfection with viral hepatitis A, C or D.(2) Coinfection with HIV.(3) Presence of Hepatoma.(4) Known presence of other malignancy.(5) Previous antiviral treatment.The diagnosis of hepatitis B will be based on standard serological assay results and HBV DNA detected with polymerase chain reaction using the Cobas Amplicor HBV Monitor Test (Roche Diagnostics inc.). This testing is part of the usual blood work regularly performed on these patients.We intend to stain the liver biopsies for quantitative assessment of apoptotic activity using three staining techniques:(1) TUNEL.(2) Immunohistochemistry for activated caspase-3, caspase-9 and cytochrome-C release.(3) Western blotting for caspase 3,6,7,8 and 9. Liver biopsies will only be performed if clinically indicated independent of this study protocol.At the time of liver biopsy, liver tissue was/will be buffered in formalin and embedded in paraffin. Tissue will also be frozen at minus 80 degrees for Western blotting. Two age-matched control groups of patients will also be randomly selected and compared to the study population. These control liver biopsies will be stained for apoptotic activity and for disease activity as well. These control groups will include patients who are:(1) HBeAg negative, unstable (elevated) ALT.(2) Healthy controls (living donor biopsies). All sections will be assessed for apoptotic activity using the appropriate technique that is specific for TUNEL, immunohistochemistry and Western blotting respectively. Liver histology will also be reviewed for grade and stage by an experienced hepatopathologist at the UHN. Necroinflammatory activity will be assessed using Ishak's hepatitis activity index and the Laennec grading system (a minor modification of the METAVIR system) will be used for assessment of hepatic fibrosis. Liver cell apoptosis assessed by the various techniques will be reported for the study group and the control groups as means +/- SEM. To compare the means between groups, ANOVA or Student's t test will be performed. Pearson's correlation coefficient will be used to measure the degree of association between apoptosis and histopathological activity on liver biopsy. Only the principal investigator will have access to personal and demographic information relating to the individuals included. Those performing pathological review and statistical analysis will be blinded to patient information.
- Conditions
- Hepatitis B
- Keywords
- Hepatitis B, apoptosis
- Medical subject headings
- Hepatitis B
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2005 (estimated)
- Study startJul 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis BStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe 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
- Observational
- Observational model
- Defined population
- Time perspective
- Other
- Enrolment
- 30 participants
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Investigators
- E.J.L (Jenny) Heathcote, MD, Principal investigator, UHN - Toronto Western Hospital, University of Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00152880
- Sponsor's protocol ID
- 05-0337-T
- Status last verified
- Sep 2005
- First submitted
- 8 Sep 2005
- Last updated
- 1 Dec 2005
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Dec 2005. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Apoptosis and Hepatitis B: The Role of Apoptosis in Patients Who Are HBeAg Negative, Have Normal ALT, and HBV DNA ≥10,000 Copies/mL
- ClinicalTrials.gov ID
- NCT00152880
- Acronym / sponsor ID
- 05-0337-T
- Conditions
- Hepatitis B
- Keywords
- Hepatitis B, apoptosis
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 30 participants
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- Jul 2005
- First posted
- 9 Sep 2005 (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.
A large number hepatitis B surface antigen positive individuals are HBeAg negative with normal liver tests. Historically, such patients were thought to have suppressed viral replication and were considered to be at low risk for complications. With the use of more sensitive technology, physicians are now able to identify a group of patients who are HBeAg negative, have normal liver enzymes, and detectable HBV DNA. Some of these patients develop signs of liver inflammation and fibrosis on biopsy. We intend to investigate whether normal, programmed cell death (apoptosis) plays a role in causing the silent liver injury in this group of patients. In other words the purpose of this study is to see whether apoptosis may be responsible for the silent liver death and injury that occurs in these so called inactive carriers who are HBeAg negative, have normal serum ALT values and HBV DNA > 10,000 copies/mL. In this study the liver biopsies would be routinely collected in the clinic and investigated for the evidence of inflammation and fibrosis, and special testing would be performed to detect for evidence of apoptosis. Around 30 patients from UHN would be participating in this study. This study will test the hypothesis that subjects who are HBeAg negative, have normal ALT and have HBV DNA ≥10,000 copies/mL will demonstrate an increased rate of apoptosis in liver tissue compared to healthy age-matched controls. If this hypothesis is confirmed, it will imply that the previous assumption that this group of patients has inactive disease is false and would implicate apoptosis as an important mechanism responsible for causing liver damage. If apoptotic activity is indeed elevated, further study of these pathways could potentially yield therapeutic interventions to inhibit apoptosis.
Detailed description
Through a retrospective chart review, patients with HBsAg who are HBeAg negative, have normal ALT, and HBV DNA >10,000 copies/mL and who have or who are about to undergo liver biopsy will be identified. These individuals will be patients at the Toronto Western Hospital Liver Clinics. Inclusion criteria:(1) HBsAg positive.(2) Stable HBeAg status for at least one year prior to biopsy.(3) Normal ALT levels (defined as <1.5 x the upper limit of normal) for at least 90 days prior to biopsy.(4) HBV DNA ≥10,000 copies/mL by PCR measured within 90 days of liver biopsy.Exclusion criteria:(1) Coinfection with viral hepatitis A, C or D.(2) Coinfection with HIV.(3) Presence of Hepatoma.(4) Known presence of other malignancy.(5) Previous antiviral treatment.The diagnosis of hepatitis B will be based on standard serological assay results and HBV DNA detected with polymerase chain reaction using the Cobas Amplicor HBV Monitor Test (Roche Diagnostics inc.). This testing is part of the usual blood work regularly performed on these patients.We intend to stain the liver biopsies for quantitative assessment of apoptotic activity using three staining techniques:(1) TUNEL.(2) Immunohistochemistry for activated caspase-3, caspase-9 and cytochrome-C release.(3) Western blotting for caspase 3,6,7,8 and 9. Liver biopsies will only be performed if clinically indicated independent of this study protocol.At the time of liver biopsy, liver tissue was/will be buffered in formalin and embedded in paraffin. Tissue will also be frozen at minus 80 degrees for Western blotting. Two age-matched control groups of patients will also be randomly selected and compared to the study population. These control liver biopsies will be stained for apoptotic activity and for disease activity as well. These control groups will include patients who are:(1) HBeAg negative, unstable (elevated) ALT.(2) Healthy controls (living donor biopsies). All sections will be assessed for apoptotic activity using the appropriate technique that is specific for TUNEL, immunohistochemistry and Western blotting respectively. Liver histology will also be reviewed for grade and stage by an experienced hepatopathologist at the UHN. Necroinflammatory activity will be assessed using Ishak's hepatitis activity index and the Laennec grading system (a minor modification of the METAVIR system) will be used for assessment of hepatic fibrosis. Liver cell apoptosis assessed by the various techniques will be reported for the study group and the control groups as means +/- SEM. To compare the means between groups, ANOVA or Student's t test will be performed. Pearson's correlation coefficient will be used to measure the degree of association between apoptosis and histopathological activity on liver biopsy. Only the principal investigator will have access to personal and demographic information relating to the individuals included. Those performing pathological review and statistical analysis will be blinded to patient information.
Study design
- Observational model
- Defined population
- Time perspective
- Other
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- HBsAg positive.
- Stable HBeAg status for at least one year prior to biopsy.
- Normal ALT levels (defined as <1.5 x the upper limit of normal) for at least 90 days prior to biopsy.
- HBV DNA ≥10,000 copies/mL by PCR measured within 90 days of liver biopsy.
- patients attending Liver Clinic at Toronto Western Hospital, Toronto, ON, Canada
Key exclusion criteria (5 listed)
- Coinfection with viral hepatitis A, C or D.
- Coinfection with HIV.
- Presence of Hepatoma.
- Known presence of other malignancy.
- Previous antiviral treatment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Dec 2005.
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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.
Brandusa Florica contact
E.J.L (Jenny) Heathcote, MD principal investigator
UHN - Toronto Western Hospital, University of Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hepatitis B, run by University Health Network, Toronto at 1 site in Canada.
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 5 inclusion and 5 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 1 Dec 2005. 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 Canada. 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?
Contact Brandusa Florica (416-603-6232), or a site near the patient. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
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 1 Dec 2005.