Clinical Trial:Lamivudine for Chronic Hepatitis B

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Lamivudine for Chronic Hepatitis B

This study is currently recruiting patients.

Sponsored by

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Purpose

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 Clinial 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.

Condition Phase

Chronic Hepatitis B

Chronic Hepatitis D

Glomerulonephritis

Polyarteritis Nodosa Phase II

MEDLINEplus related topics: Circulatory Disorders; Hepatitis; Kidney

Diseases (General); Skin Diseases (General); Vasculitis; Viral

Infections

Study Type: Interventional

Further Study Details:

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), ( extra-hepatic manifestations, © 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 and 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.

Eligibility

Genders Eligible for Study: Both

Criteria

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.

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.

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.

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.

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.

Must not be pregnant or if capable of bearing or fathering children must

practice adequate contraception.

Must not have significant systemic illnesses other than liver diseases,

including congestive heart failure, renal failure, chronic pancreatitis,

diabetes mellitus with poor control.

Must not have 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.

Must not have 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.

Must not have irreversibly severe cirrhosis as defined by Child's stage C.

Must not have the presence of anti-HIV or anti-HCV with HCV RNA in serum.

Must not have immunosuppressive therapy requiring use of more than 10 mg

of prednisone (or its equivalent) per day.

Must not have had other antiviral therapy for chronic hepatitis B within

the previous 3 months.

Must not have sensory or motor neuropathy apparent from medical history

and physical examination.

Expected Total Enrollment: 60

Location and Contact Information

land

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK),

9000 Rockville Pike Bethesda, land, 20892, United States;

Recruiting

Patient Recruitment and Public Liaison Office 1-800-411-1222

prpl@...

TTY 1-866-411-1010

More Information

Detailed Web Page

Publications

Treatment of chronic viral hepatitis

Hepatitis B e antigen, DNA polymerase activity, and infection of household

contacts with hepatitis B virus

Hepatocellular carcinoma and hepatitis B virus: a prospective study of

22,707 men in Taiwan

Study ID Numbers 950199; 95-DK-0199

Date study started September 28, 1995

Record last reviewed August 3, 2001

Last Updated August 3, 2001

NLM Identifier NCT00001457

ClinicalTrials.gov processed this record on 2001-12-26