A Pilot Trial of Simvastatin Alone and Added to Tenofovir or Entecavir for the Treatment of Chronic Hepatitis B
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- Reduction of HBV DNA by one log.
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Hepatitis B positive by HBV DNA within 180 days.
- •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.
Arms & Interventions
Simvastatin
Simvastatin orally
Intervention: Simvastatin (Drug)
Simvastatin and tenofovir
Simvastatin combined with tenofovir
Intervention: Simvastatin (Drug)
Simvastatin and tenofovir
Simvastatin combined with tenofovir
Intervention: Tenofovir (Drug)
Simvastatin and entecavir
Simvastatin combined with entecavir
Intervention: Simvastatin (Drug)
Simvastatin and entecavir
Simvastatin combined with entecavir
Intervention: Entecavir (Drug)
Outcomes
Primary Outcomes
Reduction of HBV DNA by one log.
Time Frame: 14 days
Simvastatin will be given in doses of 5,10,20,and 40mg per day
Secondary Outcomes
- Alanine aminotransferase (ALT) reduction(14 days)
Investigators
Ted Bader, MD
Director of Liver Diseases, OUHSC/VAMC
Bader, Ted, M.D.