Simvastatin for the Treatment of Chronic Hepatitis B

Study Overview
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Brief Summary
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The investigators have shown robust in vitro anti-hepatitis B activity of simvastatin alone and synergistic activity with all four FDA-approved anti-hepatitis B oral drugs tested. The investigators propose phase 1 studies in 48 chronic hepatitis B human carriers who have never been treated before. Doses of drugs will remain at or below FDA-approved dosage levels for cholesterol lowering (simvastatin) or hepatitis B (tenofovir or entecavir). Arm 1 will have simvastatin monotherapy only. Arm 2 will combine simvastatin with tenofovir. Arm 3 will combine simvastatin with entecavir. For maximum safety, the 3 arms and the dose groups in each arm will be filled consecutively and not concurrently. The definition of efficacy for simvastatin alone will be a 1 log drop of hepatitis B virus in 14 days. Efficacy for combination of drugs will require a 2 log drop of hepatitis B virus in 14 days. Numerous safety tests and stop rules are noted in the protocol.

Official Title
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A Pilot Trial of Simvastatin Alone and Added to Tenofovir or Entecavir for the Treatment of Chronic Hepatitis B

Conditions
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Hepatitis B

Intervention / Treatment
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* Drug: Simvastatin
* Drug: Tenofovir
* Drug: Entecavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hepatitis B positive by HBV DNA within 180 days. Ages 18-70. Men and non-pregnant women eligible. Veteran's eligibility or appropriate health insurance. Exclusion Criteria: Use of any anti-HBV medicine within 30 days. Decompensated cirrhosis as evidenced by esophageal varices, ascites, or encephalopathy. (grade 1 varices without history of bleeding will be allowed, if patient meets Child's-Pugh functional classification grade A). A positive urine test for marijuana or alcohol within 2 months of screening.(Allowed to repeat tests on different days, if positive first time in order to become eligible for study. Severe cardiovascular disease (ejection fraction <20%)* or uncontrolled angina. Severe pulmonary disease (FEV1 < 1.0). Chronic renal insufficiency (creatinine clearance <50 ml/min. HIV positive patients.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Simvastatin<br>Simvastatin orally | Drug: Simvastatin<br>* daily doses for 14 days<br>* Other names: Zocor;|
| Experimental: Simvastatin and tenofovir<br>Simvastatin combined with tenofovir | Drug: Simvastatin<br>* daily doses for 14 days<br>* Other names: Zocor;Drug: Tenofovir<br> <br> |
| Experimental: Simvastatin and entecavir<br>Simvastatin combined with entecavir | Drug: Simvastatin<br>* daily doses for 14 days<br>* Other names: Zocor;Drug: Entecavir<br>* Entecavir<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of HBV DNA by one log. | Simvastatin will be given in doses of 5,10,20,and 40mg per day | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alanine aminotransferase (ALT) reduction | ALT changes will be noted | 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis B, simvastatin, HBV DNA