Long-Term Lamivudine Therapy for Chronic Hepatitis B
| Status: | Completed |
|---|---|
| Conditions: | Hepatitis, Hepatitis |
| Therapuetic Areas: | Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/21/2016 |
| Start Date: | July 2005 |
| End Date: | March 2007 |
This study will evaluate the long-term safety and effectiveness of lamivudine therapy and
the possibility of stopping therapy in patients whose hepatitis B is chronic, that is, long
lasting, and which has responded to treatment. Chronic hepatitis B, caused by a virus, is a
common form of liver disease affecting about 1 million Americans and about 5 percent of the
world's population. Health effects include a continuous state of being infectious and the
risk of transmitting hepatitis to other people, symptoms of liver disease, and development
of cirrhosis-that is, severe damage to the liver-and liver cancer. Lamivudine is a
medication that blocks hepatitis B effectively but does not make it disappear completely.
Scientists believe that the immune system must also be active to rid the body of the last
traces of hepatitis B.
Patients ages 18 and older who have chronic hepatitis B and are being treated with
lamivudine may be eligible to participate in this study. They will undergo a medical history
and physical examination and will be given lamivudine in 100 mg tablets to be taken as one
tablet, once each day. Patients will be asked to return to the outpatient clinic every 3
months, when they will undergo a brief interview and measurement of vital signs-such as
blood pressure, pulse, and body weight. During the visits, they will fill out questionnaires
about any symptoms or side effects they have, and they will be seen by a doctor and have a
brief medical history and examination. There will be a collection of blood for complete
blood counts, liver enzymes, and hepatitis B virus. Extra blood tests may be done to analyze
patients' immune reactions to hepatitis B. Patients will also receive refills of their
lamivudine tablets. They will continue to be treated with lamivudine as long as it seems to
control the hepatitis infection and liver disease.
At intervals of about 1 year, patients will have ultrasound examinations, lasting about 1
hour, of the liver and abdomen. Then at intervals of about 5 years, patients will undergo
liver biopsies, which require a hospital stay of 2 to 3 days. A liver biopsy is done by
passing a needle through the skin into the liver to obtain a piece of liver about 2 inches
long and 1/16-inch in diameter. A small amount of bleeding probably occurs with most liver
biopsies. Internal bleeding is a risk, which may require that the patient stay in the
hospital a few days longer, for rest, observation and pain medicine. The biopsy provides
information that proves whether lamivudine is controlling the liver disease and preventing
it from worsening or progressing to cirrhosis.
Side effects of lamivudine include fatigue, muscle aches, fever and chills, sore throat,
nausea, stomach pain or cramps, and diarrhea. Serious side effects are rare, occurring in
less than 1% of people taking lamivudine. They include inflammation of the pancreas, nerve
damage, and buildup of lactic acid in the blood. About 25% of patients experience a
temporary worsening, or flare, of hepatitis during the first few months of treatment. If
flares are severe, it is important for researchers to determine whether they are caused by
resistance to lamivudine or by the immune system acting against the hepatitis B virus or
another liver condition. A flare of hepatitis can also occur when lamivudine is stopped,
that is, a withdrawal. In such situations, testing for hepatitis B virus levels and other
liver conditions is important. It may lead to other treatments or stopping lamivudine and
taking another medication instead. While patients are participating in the study, they will
have a careful evaluation of their hepatitis and general condition. They may have an
improvement in their disease as a result of long-term lamivudine therapy.
the possibility of stopping therapy in patients whose hepatitis B is chronic, that is, long
lasting, and which has responded to treatment. Chronic hepatitis B, caused by a virus, is a
common form of liver disease affecting about 1 million Americans and about 5 percent of the
world's population. Health effects include a continuous state of being infectious and the
risk of transmitting hepatitis to other people, symptoms of liver disease, and development
of cirrhosis-that is, severe damage to the liver-and liver cancer. Lamivudine is a
medication that blocks hepatitis B effectively but does not make it disappear completely.
Scientists believe that the immune system must also be active to rid the body of the last
traces of hepatitis B.
Patients ages 18 and older who have chronic hepatitis B and are being treated with
lamivudine may be eligible to participate in this study. They will undergo a medical history
and physical examination and will be given lamivudine in 100 mg tablets to be taken as one
tablet, once each day. Patients will be asked to return to the outpatient clinic every 3
months, when they will undergo a brief interview and measurement of vital signs-such as
blood pressure, pulse, and body weight. During the visits, they will fill out questionnaires
about any symptoms or side effects they have, and they will be seen by a doctor and have a
brief medical history and examination. There will be a collection of blood for complete
blood counts, liver enzymes, and hepatitis B virus. Extra blood tests may be done to analyze
patients' immune reactions to hepatitis B. Patients will also receive refills of their
lamivudine tablets. They will continue to be treated with lamivudine as long as it seems to
control the hepatitis infection and liver disease.
At intervals of about 1 year, patients will have ultrasound examinations, lasting about 1
hour, of the liver and abdomen. Then at intervals of about 5 years, patients will undergo
liver biopsies, which require a hospital stay of 2 to 3 days. A liver biopsy is done by
passing a needle through the skin into the liver to obtain a piece of liver about 2 inches
long and 1/16-inch in diameter. A small amount of bleeding probably occurs with most liver
biopsies. Internal bleeding is a risk, which may require that the patient stay in the
hospital a few days longer, for rest, observation and pain medicine. The biopsy provides
information that proves whether lamivudine is controlling the liver disease and preventing
it from worsening or progressing to cirrhosis.
Side effects of lamivudine include fatigue, muscle aches, fever and chills, sore throat,
nausea, stomach pain or cramps, and diarrhea. Serious side effects are rare, occurring in
less than 1% of people taking lamivudine. They include inflammation of the pancreas, nerve
damage, and buildup of lactic acid in the blood. About 25% of patients experience a
temporary worsening, or flare, of hepatitis during the first few months of treatment. If
flares are severe, it is important for researchers to determine whether they are caused by
resistance to lamivudine or by the immune system acting against the hepatitis B virus or
another liver condition. A flare of hepatitis can also occur when lamivudine is stopped,
that is, a withdrawal. In such situations, testing for hepatitis B virus levels and other
liver conditions is important. It may lead to other treatments or stopping lamivudine and
taking another medication instead. While patients are participating in the study, they will
have a careful evaluation of their hepatitis and general condition. They may have an
improvement in their disease as a result of long-term lamivudine therapy.
The major aims of this study are to evaluate the long-term efficacy and safety of lamivudine
therapy and the possibility of stopping therapy in a cohort of patients with chronic
hepatitis B who have a maintained response to treatment. Lamivudine is a nucleoside analogue
with potent activity against hepatitis B virus (HBV), which is approved for use in the
United States and is used extensively throughout the world to treat HBV and HIV infection.
Lamivudine is well tolerated and adverse events are rare. Its major shortcoming is the
development of antiviral resistance after prolonged therapy which results in loss of
effectiveness, marked by rise in viral levels and return of disease activity. Some patients,
however, have a maintained response to lamivudine therapy and in these individuals treatment
is continued indefinitely or until hepatitis B surface antigen (HBsAg) is lost and therapy
can be permanently stopped. This protocol will allow for the long-term treatment and
evaluation of these patients. Patients will be maintained on lamivudine at a dose of 100 mg
daily and seen every three months for interim medical history and serum testing for
aminotransferase levels and hepatitis B markers, with liver biopsies done every 5 years.
Lamivudine will be stopped if HBsAg is lost. The protocol also includes an option to attempt
withdrawal of therapy under controlled conditions focusing on inducing immune reactivity to
HBV and clearance of HBsAg. Patients will stop lamivudine for short periods (1 week, and
later for 2, 4 and 8 weeks) and be monitored during and for 12 weeks afterwards for
aminotransferase levels, HBV DNA levels and CD4+ and CD8+ T cell responses to HBV antigens.
Patients who demonstrate significant worsening of hepatitis will not undergo further
attempts at withdrawal. The endpoint to successful therapy is defined as loss of hepatitis B
surface antigen (HBsAg) and development of antibody (anti-HBs).
therapy and the possibility of stopping therapy in a cohort of patients with chronic
hepatitis B who have a maintained response to treatment. Lamivudine is a nucleoside analogue
with potent activity against hepatitis B virus (HBV), which is approved for use in the
United States and is used extensively throughout the world to treat HBV and HIV infection.
Lamivudine is well tolerated and adverse events are rare. Its major shortcoming is the
development of antiviral resistance after prolonged therapy which results in loss of
effectiveness, marked by rise in viral levels and return of disease activity. Some patients,
however, have a maintained response to lamivudine therapy and in these individuals treatment
is continued indefinitely or until hepatitis B surface antigen (HBsAg) is lost and therapy
can be permanently stopped. This protocol will allow for the long-term treatment and
evaluation of these patients. Patients will be maintained on lamivudine at a dose of 100 mg
daily and seen every three months for interim medical history and serum testing for
aminotransferase levels and hepatitis B markers, with liver biopsies done every 5 years.
Lamivudine will be stopped if HBsAg is lost. The protocol also includes an option to attempt
withdrawal of therapy under controlled conditions focusing on inducing immune reactivity to
HBV and clearance of HBsAg. Patients will stop lamivudine for short periods (1 week, and
later for 2, 4 and 8 weeks) and be monitored during and for 12 weeks afterwards for
aminotransferase levels, HBV DNA levels and CD4+ and CD8+ T cell responses to HBV antigens.
Patients who demonstrate significant worsening of hepatitis will not undergo further
attempts at withdrawal. The endpoint to successful therapy is defined as loss of hepatitis B
surface antigen (HBsAg) and development of antibody (anti-HBs).
- INCLUSION CRITERIA:
- Age 18 years or above, male or female
- Presence of HBsAg in serum for at least 6 months.
- Previous liver biopsy histology showing chronic hepatitis with or without cirrhosis.
- Long-term (greater than 1 year) lamivudine therapy in doses of 100 mg daily.
- Normal or near normal (less than twice the upper limit of normal) serum
aminotransferase levels.
- HBV DNA levels below 10(5) copies per ml while on lamivudine.
- Written informed consent.
EXCLUSION CRITERIA:
- In women, pregnancy, breast feeding, and, in those capable of bearing children,
inability to practice adequate contraception.
- Significant systemic illnesses other than liver disease, including congestive heart
failure, renal failure, chronic pancreatitis, or diabetes mellitus with poor control.
- Serum creatinine greater than 1.5 mg/dL and creatinine clearance less than 50 cc/min.
- A history of clinically apparent pancreatitis or evidence of subclinical 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.
- Severe cirrhosis as defined by Child's stage C (Child-Pugh score of 7 or above).
- HIV infection as indicated by presence of anti-HIV in serum.
- Chronic hepatitis C as shown by the presence of anti-HCV and 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.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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