A Randomized Study to Investigate the Presence of Tocopherol Metabolites in the Colon
- Determine the effect of high γ-tocopherol vitamin E mixture supplementation on plasma
levels of α-, γ-, and δ-tocopherols, and prostaglandin E_2 in patients planning to
undergo surgery for colorectal cancer by comparing the blood samples collected before
and after the supplementation in each of the groups and analyzing levels of tocopherols
and their metabolites in urine samples.
- Test the hypothesis that the supplementation reduces oxidative and nitrosative stress
by measuring plasma levels of F_2-isoprostane, C-reactive protein, and 3-nitrotyrosine
as well as urinary levels of 8-hydroxy-2-deoxyguanosine (8-OHdG).
- Determine the levels of α-, γ-, and δ-tocopherols in colon tissues and analyze
immunohistochemically for cell proliferation, apoptosis, β-catenin localization, RXR
expression, cyclooxygenase-2, 8-OHdG, and 3-nitrotyrosine levels in colon cancer tissue
OUTLINE: This is a multicenter study. The first 5 patients receive no supplements (to
establish laboratory standards), all other patients are randomized to 1 of 3 treatment arms.
- Arm I: Patients receive no intervention before undergoing planned surgery.
- Arm II: Patients receive oral high γ-tocopherol vitamin E mixture supplementation once
daily for 1 week before undergoing planned surgery.
- Arm III: Patients receive oral high γ-tocopherol vitamin E mixture supplementation once
daily for 2 weeks before undergoing planned surgery.
Blood and urine samples are collected at baseline and on the day of surgery for tocopherol
and biomarker analysis. A sample of colon tissue is removed during standard surgical
resection for chemical analysis. Plasma, tumor tissue, and nontumorous tissues are analyzed
for levels of F_2-isoprostane, 8-OHdG, 3-nitrotyrosine, and prostaglandin E_2 via enzyme
immunoassays and for levels of α-, γ-, and δ-tocopherols via HPLC.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Plasma and urine levels of α-, γ-, and δ-tocopherols, and prostaglandin E2
Susan Goodin, PharmD, FCCP, BCOP
Cancer Institute of New Jersey
United States: Institutional Review Board
|Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School||New Brunswick, New Jersey 08903|