Evaluating Three Grams Daily Valacyclovir in Patients With Chronic Hepatitis C and HSV-2 Infection (Phase I)
Evaluating Three Grams Daily Valacyclovir in Patients With Chronic Hepatitis C and HSV-2 Infection (Phase I)
The purpose of this study is to study the effects of valacyclovir on patients who have
 hepatitis C and antibodies to herpes simplex type-2. Herpes simplex type 2 is a virus which
 causes genital herpes. Some persons with genital herpes have sores in their private areas but
 most persons do not have any symptoms at all. Valacyclovir is a medication which is commonly
 used to treat or prevent outbreaks of genital herpes. This medication is already approved by
 the Food and Drug Administration to treat genital herpes. Valacyclovir has not been approved
 to treat chronic hepatitis C.

 The study will take 16 weeks. Participants will be assigned to take either the study drug,
 valacyclovir, or a sugar pill that looks exactly like valacyclovir. The researchers and the
 persons participating will not know which medication they are receiving. Study visits will
 occur every two weeks and will take approximately 3-45 minutes. All study visits will occur
 at the G.V. Sonny Montgomery VA Medical Center.
Study is a randomized, double-blinded, placebo-controlled, Phase II clinical trial.
 Participants will be recruited while attending regularly scheduled clinic appointments at the
 Jackson VA Medical Center. Baseline Visit. Participants will be randomized 1:1 in groups of
 10 to receive valacyclovir 1.5 gram orally twice daily or matching placebo. Enrolled
 participants will complete 12 weeks of assigned therapy.

 At the initial visit, participants will complete a short questionnaire detailing past
 medical/social history and relevant symptoms. Venipuncture will be performed to obtain
 samples for the laboratory tests. The baseline de-identified serum sample will be obtained
 from the clinical lab and stored in research-approved freezer space for future confirmation
 with the Biokit HSV-2 rapid assay. Follow-up visits will be scheduled at two-week intervals
 after baseline. At each visit, pill-count, compliance and tolerability of medications will be
 assessed using a short questionnaire. Venipuncture will be performed every four weeks (i.e.,
 at every other follow-up visit) to provide samples for the tests described below. Information
 from each study visit will be recorded into the chart by the PI or Research Assistant (RA)
 and entered into an encrypted database on a VA server. Laboratory Tests. HSV-2 infection will
 be confirmed by performing the Biokit HSV-2 rapid assay on the baseline stored serum sample
 using methods previously described in this proposal. Laboratory tests will include 1)
 complete blood count, comprehensive metabolic profile, and quantitative hepatitis C virus
 (HCV) RNA; and 2) Focus HerpeSelect HSV-1 Immunoglobulin G (IgG) for participants who were
 seronegative for HSV-1 at baseline. Patient's IL28-B genotype will also be assessed at
 baseline. The PI will review all laboratory parameters.

 Baseline characteristics between the groups will be compared using appropriate parametric
 tests. Analysis will be intention to treat with the inclusion of all subjects who were
 randomized to drug or placebo. The primary outcome is change in HCV viral load in the
 treatment group compared with placebo. Because the investigators are expecting a 0.5 log10
 decline in HCV viral load, the investigators will use one-sided parametric tests. All viral
 loads will be log10-transformed before analysis.
Inclusion Criteria:

 -  Documentation of chronic HCV infection with genotype testing and previous positive
 HerpeSelect HSV-2 IgG assay

 Exclusion Criteria:

 -  Antiherpes or immunomodulatory therapy during the past 30 days

 -  HIV or chronic hepatitis B infection

 -  Decompensated liver disease (ascites, hepatic encephalopathy, coagulopathy,
 jaundice/icterus)

 -  Creatinine clearance < 50 ml/min.

 -  Female subject who is pregnant or nursing

 -  Gastrointestinal disorder which might result in malabsorption of valacyclovir

 -  History of erythema multiforme major, thrombotic thrombocytopenia purpura or hemolytic
 uremic syndrome

 -  Therapy for hepatitis C in the previous 6 months