Hepatitis C
Conditions
Brief summary
Hepatitis C is the most common reason for liver transplantation in the United States and affects nearly 4 million Americans. Treatments for hepatitis C are available but are poorly tolerated and are not always effective. Morbidity and mortality from hepatitis C are related to the development and progression of hepatic fibrosis to cirrhosis and end stage liver disease. Efforts to block progression of liver disease would thus result in prevention of morbidity and mortality as well as costs incurred by the health system in the care of these conditions. Scar tissue in the liver is secreted by a type of cell, called the stellate cell, in an activated state. This cell carries a receptor for angiotensin, a hormone, when activated. If this receptor is blocked, the cell becomes inactive and does not participate in scar tissue formation. Thus, we hypothesize that using a drug such as candesartan, which blocks angiotensin receptors, should result in less scar tissue formation in the livers of patients with hepatitis C.
Interventions
DRUGCandesartan
16mg po daily
DRUGPlacebo
once daily
Sponsors
University of California, Davis
Kaiser Permanente
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Adults, age 21 and older * Patients with viral hepatitis C that are not on interferon based therapy. * Detectable viral load * Baseline biopsy within six months or willing to undergo biopsy prior to drug initiation * At least grade 2 inflammation on biopsy, fibrosis of stage 1 or higher * Willing to undergo biopsy at the end of treatment * No interferon for at least 6 months prior to or after initial biopsy for study
Exclusion criteria
* Renal impairment defined by a serum creatinine of \>1.8 * Congestive heart failure * Hepatocellular cancer * Concurrent treatment with pentoxyfylline, steroids, interferon alpha or interferon gamma. * Active psychosis (affective disorders without loss of reality testing acceptable) * Active IV drug use * Prior liver transplant * Pregnancy * Decompensated cirrhosis as defined by the presence of ascites, hepatic encephalopathy or coagulopathy with an INR\>1.4 * HIV seropositivity * Hypotension defined by a baseline systolic blood pressure of less than 90mm of mercury * Contraindication to ARB use or allergy to medication * Treatment with potassium sparing diuretics
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary: • Stellate cell activity by alpha SMA stain quantitated by morphometry | 48 weeks |
| • Hepatic fibrosis by morphometry | 48 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Surrogate markers for fibrosis (liver TGF-beta levels, serum procollagen-III peptide levels) | 48 weeks |
| Functional status- Albumin, INR, T. Bilirubin, MELD score | 48 weeks |
Countries
United States
Outcome results
None listed