Chronic Hepatitis C Infection
Conditions
Keywords
Chronic hepatitis C infection
Brief summary
The purpose of this study is to examine the effects of valacyclovir in patients who have chronic hepatitis C, antibodies to herpes simplex type 1 infection but do not have antibodies to herpes simplex type 2 infection. Herpes simplex type 1 infection commonly causes cold sores or fever blisters, also known as herpes labialis, but most persons do not have any symptoms at all. Valacyclovir is a medication which is approved by the Food and Drug administration to treat herpes labialis. Valacyclovir has not been approved to treat chronic hepatitis C infection. 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 patients will not know which medication they are receiving. Study visits will occur every two weeks and will take approximately 30-45 minutes. All study visits will occur at the G.V. Sonny Montgomery VA Medical Center in Jackson, Mississippi.
Detailed description
This is a randomized double-blind placebo-controlled clinical trial evaluating the effect of 500 mg valacyclovir twice daily on HCV viral load in HSV-1/HCV co-infected patients seronegative for HSV-2. Potential participants will be recruited from the Jackson VAMC viral hepatitis clinics. Eligible individuals will be invited to enroll in the study in a noncoercive manner. Study personnel will obtain full informed consent. Using a computer generation randomization scheme, patients will be randomized 1:1 in blocks of 4 to receive valacyclovir 500 mg po twice daily or matching placebo. Patients will be counseled on the signs and symptoms of herpes labialis and genital herpes and complete a questionnaire to document medical/social history. Venipuncture will be performed every four weeks (i.e., at every other follow-up visit) to monitor complete blood cell count, liver function tests, serum levels of hepatitis C RNA and Herpeselect IgG HSV-2 ELISA. A de-identified baseline serum sample will be collected and stored in VA approved research space for future testing. At each visit, pill-count and tolerability of medications will be assessed. Patients will be asked about signs or symptoms of genital herpes. Data will be kept in a study chart labeled with the participant's coded study number in a locked office. Information from each study visit will be recorded into the chart by the PI or RA and entered into an encrypted database on a secure VA server. Baseline characteristics of the placebo and intervention group will be compared using appropriate parametric tests. HCV viral loads will be log10 transformed and analyzed using an intention to treat model.
Interventions
DRUGValacyclovir
Valacyclovir 500 mg po bid
DRUGPlacebo
Placebo tablet twice daily
Sponsors
GlaxoSmithKline
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Chronic hepatitis C infection with a detectable HCV RNA in the serum on two occasions, 6 months apart * Focus HSV-2 IgG negative and Focus HSV-1 IgG positive, using manufacturer's cut-offs
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, * Allergy to valacyclovir or related drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HCV RNA Viral Load | Baseline, 12 weeks | Measure change in HCV RNA viral load in treatment group as compared with placebo |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Valacyclovir Valacyclovir 500 mg po bid
Valacyclovir: Valacyclovir 500 mg po bid | 10 |
| Placebo Matching placebo twice daily
Placebo: Placebo tablet twice daily | 9 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 2 |
Baseline characteristics
| Characteristic | Placebo | Valacyclovir | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 10 Participants | 19 Participants |
| Age, Continuous | 57 years STANDARD_DEVIATION 3 | 55 years STANDARD_DEVIATION 2 | 56 years STANDARD_DEVIATION 2 |
| Region of Enrollment United States | 9 participants | 10 participants | 19 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 9 Participants | 10 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 10 | 0 / 9 |
| serious Total, serious adverse events | 0 / 10 | 0 / 9 |
Outcome results
Primary
Change in HCV RNA Viral Load
Measure change in HCV RNA viral load in treatment group as compared with placebo
Time frame: Baseline, 12 weeks
Population: patients who completed 12 weeks of follow up
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Valacyclovir | Change in HCV RNA Viral Load | .24 log(IU/mL) | Standard Deviation 0.2 |
| Placebo | Change in HCV RNA Viral Load | .08 log(IU/mL) | Standard Deviation 0.01 |
p-value: 0.05Fisher Exact