Simvastatin for the Treatment of Chronic Hepatitis B - Full Text View

Sponsor:	Bader, Ted, M.D.
Information provided by:	Bader, Ted, M.D.
ClinicalTrials.gov Identifier:	NCT00994773

Purpose

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.

Condition	Intervention	Phase
Hepatitis B	Drug: Simvastatin Drug: Tenofovir Drug: Entecavir	Phase I

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Pilot Trial of Simvastatin Alone and Added to Tenofovir or Entecavir for the Treatment of Chronic Hepatitis B

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis B

Drug Information available for: Simvastatin Entecavir Tenofovir Tenofovir disoproxil Tenofovir Disoproxil Fumarate Recombinant hepatitis B vaccine Hepatitis B Vaccines Hepatitis A Vaccines

U.S. FDA Resources

Further study details as provided by Bader, Ted, M.D.:

Primary Outcome Measures:

Reduction of HBV DNA by one log. [ Time Frame: 14 days ] [ Designated as safety issue: No ]
Simvastatin will be given in doses of 5, 10, 20, 40 and 80 mg per day

Secondary Outcome Measures:

Alanine aminotransferase (ALT) reduction [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
ALT changes will be noted

Estimated Enrollment:	48
Study Start Date:	January 2010
Estimated Study Completion Date:	January 2014
Estimated Primary Completion Date:	October 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Simvastatin Simvastatin orally	Drug: Simvastatin daily doses for 14 days Other Name: Zocor
Experimental: Simvastatin and tenofovir Simvastatin combined with tenofovir	Drug: Simvastatin daily doses for 14 days Other Name: Zocor Drug: Tenofovir
Experimental: Simvastatin and entecavir Simvastatin combined with entecavir	Drug: Simvastatin daily doses for 14 days Other Name: Zocor Drug: Entecavir Entecavir

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00994773

Contacts

Contact: Paula Allen, MA	405-456-3982	Paula.Allen@va.gov
Contact: Joe Cardello, PA	405-456-3982	Joe-Cardello@va.gov

Locations

United States, Oklahoma
VA Medical Center	Recruiting
Oklahoma City, Oklahoma, United States, 74104
Contact: Paula Allen, MA 405-456-3982 Paula.Allen@va.gov
Principal Investigator: Ted Bader, M.D.

Sponsors and Collaborators

Bader, Ted, M.D.

Investigators

Principal Investigator:

Teddy Bader, M.D.

University of Oklahoma

More Information

No publications provided

Responsible Party:	Ted Bader, M.D., Director of Liver Diseases,, University of Oklahoma Health Sciences Center/VA Medical Center
ClinicalTrials.gov Identifier:	NCT00994773 History of Changes
Other Study ID Numbers:	HBV 106707
Study First Received:	October 10, 2009
Last Updated:	June 14, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by Bader, Ted, M.D.:

Hepatitis B
simvastatin
HBV DNA

Additional relevant MeSH terms:

Hepatitis
Hepatitis A
Hepatitis B
Hepatitis, Chronic
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Simvastatin

Tenofovir
Tenofovir disoproxil
Entecavir
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Enzyme Inhibitors
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Anti-Retroviral Agents

ClinicalTrials.gov processed this record on February 09, 2012