Clinical Trial: S-Adenosyl-L-Methionine Disulphate P-Toluene-Sulfonate in Preventing Liver Cancer in Patients With Chronic Hepatitis C Infection

Study Status: Active, not recruiting
Recruit Status: Unknown status
Study Type: Interventional

Official Title: 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 Hepatiti

Brief Summary: This randomized phase II trial studies how well S-Adenosyl-L-Methionine Disulphate P-Toluene-Sulfonate (SAMe) works compared to a placebo in preventing liver cancer in patients with chronic hepatitis C infection. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of SAMe may keep cancer from forming in patients with advanced liver disease

Detailed Summary:

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: Pat
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Change in serum AFP levels [ Time Frame: Baseline to week 24 ]

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.


Original Primary Outcome: Change in serum alpha-fetoprotein levels (AFP) from baseline (week 0) to follow-up at week 24

Current Secondary Outcome:

  • Treatment-related changes in additional serum markers for hepatocellular carcinoma [ Time Frame: Baseline to week 24 ]
    DCP assay will be performed by Wako Laboratories. AFP-L3 assay will be performed by Wako Laboratories using their LiBASys platform.
  • Change in markers of liver disease [ Time Frame: Baseline to week 24 ]
    ALT and AST measurements will be performed in a College of American Pathologists (CAP)-certified lab using FDA-approved assays. The hepatitis C viral load will be measured in a CAP-certified clinical laboratory using an FDA-approved assay (quantitative assay).
  • Changes in markers of oxidative stress [ Time Frame: Baseline (week 0) to week 24 ]
    Serum TNF-alpha will be determined by ELISA with the use of R&D Systems Quantikine High Sensitivity Kit. 8-epi-Prostaglandin F2a is extracted from urine using the C18 Sep Pak and Silica Sep Pak column method. Urine 8-isoprostane concentrations will be determined by ELISA using the BIOYTECH 8-Isoprostane kit. Plasma MDA and 4-HNE will be measured by high performance liquid chromatography (HPLC).
  • Change in SAMe metabolites [ Time Frame: Baseline to week 24 ]
    Plasma GSH, methionine and homocysteine will be measured using HPLC with fluorescence detection.
  • Safety and tolerability of SAMe [ Time Frame: Up to week 24 ]
  • Changes in quality of life [ Time Frame: Baseline to week 24 ]
    Measured using the Short Form (SF)-36 Health Survey (Version II) and the Chronic Liver Disease Questionnaire.


Original Secondary Outcome:

  • Change from baseline to week 24 in other serum markers of hepatocellular carcinoma (i.e., des-gamma carboxyprothrombin or AFP-L3)
  • Change from baseline to week 24 in markers of liver disease (e.g., serum ALT and AST, albumin, and bilirubin) and in hepatitis C viral load
  • Change from baseline to week 24 in markers of oxidative stress (e.g., serum TNF-alpha, malondialdehyde, glutathione, 4-HNE isoprostane, urine F2 isoprostane)
  • Change from baseline to week 24 in SAMe metabolites (e.g., glutathione, methionine, homocysteine, and S-adenosylmethionine)
  • Safety and tolerability as assessed by NCI CTCAE v3.0
  • Health-Related Quality of life as measured at baseline and week 24 by the SF-36 Health Survey (version II) and the Chronic Liver Disease Questionnaire


Information By: National Cancer Institute (NCI)

Dates:
Date Received: August 6, 2007
Date Started: October 2007
Date Completion: December 2013
Last Updated: February 15, 2013
Last Verified: February 2013