NCT00120354

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
50

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Jul 2005

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 11, 2005

Completed
4 days until next milestone

First Submitted

Initial submission to the registry

July 15, 2005

Completed
Same day until next milestone

First Posted

Study publicly available on registry

July 15, 2005

Completed
1.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 31, 2007

Completed
Last Updated

July 2, 2017

Status Verified

March 31, 2007

First QC Date

July 15, 2005

Last Update Submit

June 30, 2017

Conditions

Keywords

Hepatitis B VirusAntiviral ResistanceDrug WithdrawalImmune ResponseHepatitis B Surface AntigenLiver BiopsyHepatitis B

Interventions

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

  • Lok AS, McMahon BJ; Practice Guidelines Committee, American Association for the Study of Liver Diseases (AASLD). Chronic hepatitis B: update of recommendations. Hepatology. 2004 Mar;39(3):857-61. doi: 10.1002/hep.20110. No abstract available.

    PMID: 14999707BACKGROUND

MeSH Terms

Conditions

Hepatitis B, ChronicHepatitis BSubstance Withdrawal Syndrome

Interventions

Hematologic Tests

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsHepadnaviridae InfectionsDNA Virus InfectionsVirus DiseasesHepatitis, Viral, HumanHepatitis, ChronicHepatitisLiver DiseasesDigestive System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsSubstance-Related DisordersChemically-Induced DisordersMental Disorders

Intervention Hierarchy (Ancestors)

Clinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisInvestigative Techniques

Study Design

Study Type
interventional
Phase
phase 4
Purpose
TREATMENT
Sponsor Type
NIH

Study Record Dates

First Submitted

July 15, 2005

First Posted

July 15, 2005

Study Start

July 11, 2005

Study Completion

March 31, 2007

Last Updated

July 2, 2017

Record last verified: 2007-03-31

Locations