A Phase II, Randomized, Controlled Trial of The Safety and Efficacy of S-Adenosyl-L-Methionine Disulphate P-Toluene-Sulfonate (SAMe) in Reducing Serum Alpha-Fetoprotein (AFP) in Patients With Hepatitis C and Moderately Elevated AFP
PRIMARY OBJECTIVE:
I. To determine whether treatment with SAMe for 24 weeks reduces serum level of
alpha-fetoprotein (AFP) in patients with advanced liver disease due to chronic hepatitis C.
SECONDARY OBJECTIVE:
I. To determine whether treatment with SAMe for 24 weeks reduces serum levels of des-gamma
carboxyprothrombin (DCP) and alpha-fetoprotein-L3 (AFP-L3) in patients with advanced liver
disease due to chronic hepatitis C (hepatocellular carcinoma tumor markers).
II. To determine whether treatment with SAMe for 24 weeks alters biochemical markers of
liver disease (e.g., serum alanine aminotransferase [ALT], aspartate aminotransferase [AST],
albumin, or bilirubin, etc.) and hepatitis C viral load in patients with advanced liver
disease due to chronic hepatitis C (hepatitis C liver disease).
III. To determine whether treatment with SAMe for 24 weeks reduces serum levels of tumor
necrosis factor-alpha (TNF-alpha), plasma levels of malondialdehyde (MDA), 4-hydroxynonenal
(4-HNE) and urine levels of F2-isoprostane in patients with advanced liver disease due to
chronic hepatitis C (oxidative stress).
IV. To determine whether treatment with SAMe for 24 weeks reduces plasma levels of
methionine and homocysteine and increases plasma glutathione (GSH) and SAMe in patients with
advanced liver disease due to chronic hepatitis C (SAMe metabolites).
V. To determine the safety, tolerability and quality of life of SAMe treatment (up to 2,400
mg/day) for 24 weeks in patients with advanced liver disease due to chronic hepatitis C.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive SAMe orally (PO) twice daily (BID) for 24 weeks in the absence of
disease progression or unacceptable toxicity.
ARM II: Patients receive placebo PO once daily (QD) for weeks 1-4, PO BID for weeks 5-8, and
PO three times daily (TID) for weeks 9-24 in the absence of disease progression or
unacceptable toxicity.
After completion of study treatment, patients are followed up at 6 weeks.
Interventional
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention
Change in serum AFP levels
Measured using an Food and Drug Administration (FDA)-approved assay. Mean change over time (and 95% confidence intervals) for the SAMe and placebo groups will be estimated. Differences in the change over time between the treated and control groups will be tested using a two-group repeated measures analysis of variance model.
Baseline to week 24
No
John Hoefs
Principal Investigator
Chao Family Comprehensive Cancer Center
United States: Food and Drug Administration
NCI-2009-00897
NCT00513461
October 2007
December 2013
Name | Location |
---|---|
Chao Family Comprehensive Cancer Center | Orange, California 92868 |
University of California at San Diego | La Jolla, California 92093 |
University of Arizona Health Sciences Center | Tucson, Arizona 85724 |
Veterans Administration Long Beach Medical Center | Long Beach, California 90822 |
Veterans Administration Los Angeles Healthcare System | Los Angeles, California 90073 |