Chronic Hepatitis BPhase 2NCT00001457
Lamivudine for Chronic Hepatitis B
A Phase 2 study testing Lamivudine in people with Chronic Hepatitis B and Chronic Hepatitis D, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
Trial summary
Chronic hepatitis B is a disease of the liver caused by the hepatitis B virus. It affects nearly 1 million Americans. Approximately 25% of patients with chronic hepatitis B will develop liver cirrhosis and 5% of patients will develop liver cancer. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Chronic Hepatitis B, Chronic Hepatitis D, Glomerulonephritis
- What is being tested?
- Lamivudine
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 1995to Sep 2005
- Phase
- Phase 2
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age 18 years or above, male or female.
- Known presence of HBsAg in serum for at least 6 months.
- Liver biopsy histology showing chronic hepatitis with or without cirrhosis.
- Previous therapy with alpha interferon without a lasting effect or intolerance to alpha interferon, due to side effects.
- Written informed consent.
- Group A: For patients with chronic hepatitis B with atypical serology: absence of HBeAg from serum despite elevations in serum aminotransferases, such as that the average levels are greater than 55 U/L (approximately 1.3 times the upper limit of the normal range) based upon two determinations taken at least one month apart during the 6 months before entry.
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- Group B: For patients with glomerulonephritis: proteinuria of greater than 1 gm per 24 hours. For patients with polyarteritis, radiological proof of arteritis and involvement of at least on organ system outside of the liver.
- Group C: For patients with chronic delta hepatitis: anti-HDV in serum and HDV antigen in liver biopsy or HDV RNA in serum and elevations in serum aminotransferases, such that the average levels are greater than 55 U/L based upon two determinations taken at least one month apart during the 6 months before entry.
- Group D: For patients with chronic hepatitis B and typical serology: HBeAg and HBV DNA in serum but ineligibility to enter the multicenter trial of lamivudine either because of previous receipt of interferon and intolerable side effects, refusal to receive interferon again, because of normal serum aminotransferases, or lack of availability of the trial.
Who cannot join
- Pregnant or if capable of bearing or fathering children must practice adequate contraception.
- Significant systemic illnesses other than liver diseases, including congestive heart failure, renal failure, chronic pancreatitis, diabetes mellitus with poor control.
- Pre-existing bone marrow compromise: hematocrit must be greater than 30%, white blood cell count must be greater than 2000 mm(3), platelets must be greater than 70,000 mm(3).
- Creatinine clearance must be greater than 50 cc/min.
- A history of clinically apparent pancreatitis or evidence of subclinically pancreatitis as shown by serum amylase values twice the upper limits of the normal range and abnormalities of the pancreas on computerized tomography or other imaging studies of the abdomen.
- Irreversibly severe cirrhosis as defined by Child's stage C.
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- Presence of anti-HIV or anti-HCV with HCV RNA in serum.
- Immunosuppressive therapy requiring use of more than 10 mg of prednisone (or its equivalent) per day.
- Other antiviral therapy for chronic hepatitis B within the previous 3 months.
- Sensory or motor neuropathy apparent from medical history and physical examination.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Bethesda, Maryland, 20892
About this study
Chronic hepatitis B is a disease of the liver caused by the hepatitis B virus. It affects nearly 1 million Americans. Approximately 25% of patients with chronic hepatitis B will develop liver cirrhosis and 5% of patients will develop liver cancer.
Presently, two medications have been shown effective in the treatment of hepatitis B: lamivudine and alpha interferon. Alpha interferon (an antiviral drug that acts through the immune system) is given by injection once daily or three times a week for four to six months. Lamivudine (also known as 3-thiacytidine: 3TC) is an antiviral medication given as a pill once a day for twelve months. These treatments have been known to provide long-term improvement in one third of patients receiving them.
Read more
In previous research, the drug lamivudine was shown to stop the growth of the hepatitis B virus and to lead marked decreases in the levels of hepatitis B virus and to improvements in the disease in 50 to 70% of patients. However, once lamivudine therapy was discontinued the virus returned to levels noted before the therapy began. In those studies lamivudine was given for 3 to 12 months then discontinued. This study will investigate the safety and effectiveness of long-term therapy with lamivudine.
This study will select 60 patients diagnosed with hepatitis B. After a thorough medical examination and liver biopsy, subjects will be given lamivudine. The drug will be taken by mouth in tablet form (100 mg) once a day for up to 5 years. Subjects will undergo regular check-ups and after 1 year of therapy be admitted to the Clinical Center for another medical examination and liver biopsy to assess progress. Patients who have benefitted from the therapy will continue taking the medication for up to 5 years. A third liver biopsy will be done during the last year of treatment. The effectiveness of lamivudine will be determined by whether levels of hepatitis B virus decrease in the blood, whether liver enzymes improve, and whether inflammation and scarring decreases in the liver biopsies.
Read the detailed description
To assess the safety, antiviral activity and clinical benefit of lamivudine (3-thiacytidine: 3TC) in chronic hepatitis B, we will treat 60 patients with oral lamivudine in a dose of 100 mg daily for up to five years. Lamivudine is a nucleoside analogue which is used extensively in patients with HIV infection and is being studied in controlled trials in chronic hepatitis B. In this study, we will evaluate lamivudine in patients with four different forms of chronic hepatitis B: (A) Atypical serology (HBeAg negative), (B) extra-hepatic manifestations, (C) chronic delta hepatitis, (D) typical HBeAg- positive chronic hepatitis B. After evaluation and liver biopsy, patients will receive lamivudine, 100 mg orally once daily for 1 year, being monitored at regular intervals for symptoms of liver disease, side effects of lamivudine, serum biochemical and hematologic indices, and serologic markers of hepatitis B (and D) virus replication. At one year, patients will have a repeat medical evaluation and liver biopsy. If there is virologic, biochemical or histologic evidence of benefit, therapy will be continued thereafter for up to 5 years. Patients who develop viral resistance to lamivudine may be offered therapy with higher doses of lamivudine (300 mg per day). The activity of lamivudine will be assessed by changes in levels of HBV DNA or HDV RNA during treatment and its efficacy by loss of viral markers and improvements in aminotransferases and liver histology.
- Being tested
- Lamivudine
- Keywords
- Nucleoside Analogues, Delta Hepatitis, Glomerulonephritis, Polyarteritis Nodosa, Hepatitis Mutants, 3TC, Chronic Hepatitis B, Chronic Hepatitis D, Cirrhosis, Lamivudine
- Medical subject headings
- Hepatitis B, Chronic, Hepatitis D, Chronic, Glomerulonephritis, Polyarteritis Nodosa, Hepatitis D, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LamivudineDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study startSep 1995
- Study completionSep 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Chronic Hepatitis BStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The 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 2
- Primary purpose
- Treatment
- Enrolment
- 60 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001457
- Sponsor's protocol ID
- 950199
- Other IDs
- 95-DK-0199
- Status last verified
- Sep 2005
- First submitted
- 3 Nov 1999
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Hoofnagle JH, di Bisceglie AM. The treatment of chronic viral hepatitis. N Engl J Med. 1997 Jan 30;336(5):347-56. doi: 10.1056/NEJM199701303360507. No abstract available.
PubMed 9011789Perrillo RP, Gelb L, Campbell C, Wellinghoff W, Ellis FR, Overby L, Aach RD. Hepatitis B e antigen, DNA polymerase activity, and infection of household contacts with hepatitis B virus. Gastroenterology. 1979 Jun;76(6):1319-25.
PubMed 437428Beasley RP, Hwang LY, Lin CC, Chien CS. Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22 707 men in Taiwan. Lancet. 1981 Nov 21;2(8256):1129-33. doi: 10.1016/s0140-6736(81)90585-7. No abstract available.
PubMed 6118576
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lamivudine for Chronic Hepatitis B
- ClinicalTrials.gov ID
- NCT00001457
- Acronym / sponsor ID
- 950199
- Keywords
- Nucleoside Analogues, Delta Hepatitis, Glomerulonephritis, Polyarteritis Nodosa, Hepatitis Mutants, 3TC, Chronic Hepatitis B, Chronic Hepatitis D
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Study start
- Sep 1995
- Study completion
- Sep 2005
- First posted
- 4 Nov 1999 (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.
Chronic hepatitis B is a disease of the liver caused by the hepatitis B virus. It affects nearly 1 million Americans. Approximately 25% of patients with chronic hepatitis B will develop liver cirrhosis and 5% of patients will develop liver cancer.
Presently, two medications have been shown effective in the treatment of hepatitis B: lamivudine and alpha interferon. Alpha interferon (an antiviral drug that acts through the immune system) is given by injection once daily or three times a week for four to six months. Lamivudine (also known as 3-thiacytidine: 3TC) is an antiviral medication given as a pill once a day for twelve months. These treatments have been known to provide long-term improvement in one third of patients receiving them.
In previous research, the drug lamivudine was shown to stop the growth of the hepatitis B virus and to lead marked decreases in the levels of hepatitis B virus and to improvements in the disease in 50 to 70% of patients. However, once lamivudine therapy was discontinued the virus returned to levels noted before the therapy began. In those studies lamivudine was given for 3 to 12 months then discontinued. This study will investigate the safety and effectiveness of long-term therapy with lamivudine.
This study will select 60 patients diagnosed with hepatitis B. After a thorough medical examination and liver biopsy, subjects will be given lamivudine. The drug will be taken by mouth in tablet form (100 mg) once a day for up to 5 years. Subjects will undergo regular check-ups and after 1 year of therapy be admitted to the Clinical Center for another medical examination and liver biopsy to assess progress. Patients who have benefitted from the therapy will continue taking the medication for up to 5 years. A third liver biopsy will be done during the last year of treatment. The effectiveness of lamivudine will be determined by whether levels of hepatitis B virus decrease in the blood, whether liver enzymes improve, and whether inflammation and scarring decreases in the liver biopsies.
Detailed description
To assess the safety, antiviral activity and clinical benefit of lamivudine (3-thiacytidine: 3TC) in chronic hepatitis B, we will treat 60 patients with oral lamivudine in a dose of 100 mg daily for up to five years. Lamivudine is a nucleoside analogue which is used extensively in patients with HIV infection and is being studied in controlled trials in chronic hepatitis B. In this study, we will evaluate lamivudine in patients with four different forms of chronic hepatitis B: (A) Atypical serology (HBeAg negative), (B) extra-hepatic manifestations, (C) chronic delta hepatitis, (D) typical HBeAg- positive chronic hepatitis B. After evaluation and liver biopsy, patients will receive lamivudine, 100 mg orally once daily for 1 year, being monitored at regular intervals for symptoms of liver disease, side effects of lamivudine, serum biochemical and hematologic indices, and serologic markers of hepatitis B (and D) virus replication. At one year, patients will have a repeat medical evaluation and liver biopsy. If there is virologic, biochemical or histologic evidence of benefit, therapy will be continued thereafter for up to 5 years. Patients who develop viral resistance to lamivudine may be offered therapy with higher doses of lamivudine (300 mg per day). The activity of lamivudine will be assessed by changes in levels of HBV DNA or HDV RNA during treatment and its efficacy by loss of viral markers and improvements in aminotransferases and liver histology.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Age 18 years or above, male or female.
- Known presence of HBsAg in serum for at least 6 months.
- Liver biopsy histology showing chronic hepatitis with or without cirrhosis.
- Previous therapy with alpha interferon without a lasting effect or intolerance to alpha interferon, due to side effects.
- Written informed consent.
Key exclusion criteria (10 listed)
- Pregnant or if capable of bearing or fathering children must practice adequate contraception.
- Significant systemic illnesses other than liver diseases, including congestive heart failure, renal failure, chronic pancreatitis, diabetes mellitus with poor control.
- Pre-existing bone marrow compromise: hematocrit must be greater than 30%, white blood cell count must be greater than 2000 mm(3), platelets must be greater than 70,000 mm(3).
- Creatinine clearance must be greater than 50 cc/min.
- A history of clinically apparent pancreatitis or evidence of subclinically pancreatitis as shown by serum amylase values twice the upper limits of the normal range and abnormalities of the pancreas on computerized tomography or other imaging studies of the abdomen.
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 |
|---|---|---|
| Lamivudine | Drug | – |
Primary outcome
Not reported in the source record.
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 4 Mar 2008.
- Background: PubMed 9011789Hoofnagle JH, di Bisceglie AM. The treatment of chronic viral hepatitis. N Engl J Med. 1997 Jan 30;336(5):347-56. doi: 10.1056/NEJM199701303360507. No abstract available.
- Background: PubMed 437428Perrillo RP, Gelb L, Campbell C, Wellinghoff W, Ellis FR, Overby L, Aach RD. Hepatitis B e antigen, DNA polymerase activity, and infection of household contacts with hepatitis B virus. Gastroenterology. 1979 Jun;76(6):1319-25.
- Background: PubMed 6118576Beasley RP, Hwang LY, Lin CC, Chien CS. Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22 707 men in Taiwan. Lancet. 1981 Nov 21;2(8256):1129-33. doi: 10.1016/s0140-6736(81)90585-7. No abstract available.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lamivudine in people with Chronic Hepatitis B and Chronic Hepatitis D, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
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 9 inclusion and 10 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 4 Mar 2008. 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 United States. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001457, which also lists 3 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 4 Mar 2008.