A Randomized Study to Investigate the Presence of Tocopherol Metabolites in the Prostate
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 65
- Locations
- 1
- Primary Endpoint
- Effect of tocopherol supplementation on plasma and urine levels of α-, γ-, and δ-tocopherols, PSA, and prostaglandin E2
Study Overview
Brief Summary
RATIONALE: Vitamin E supplements may stop or delay the development of prostate cancer in patients who are at risk of prostate cancer or who have prostate cancer. It is not yet known which vitamin E regimen is more effective in preventing prostate cancer.
PURPOSE: This randomized phase I trial is comparing vitamin E supplement regimens to see how well they work in preventing cancer in patients at risk of prostate cancer or who have prostate cancer.
Detailed Description
OBJECTIVES:
- Determine the effect of tocopherol supplementation on plasma and urine levels of α-, γ-, and δ-tocopherols, PSA, and prostaglandin E_2 by comparing the blood and urine samples collected before and after the supplementation in patients with prostate cancer.
- Test the hypothesis that the supplementation reduced 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 prostate tissues and analyze immunohistochemically (IHC) for cell proliferation, apoptosis, cyclooxygenase-2, 8-OHdG, and 3-nitropyrosine levels in prostate cancer/tissue slides.
OUTLINE: Patients are randomized into 1 of 3 arms.
- Arm I: Patients receive no supplementation.
- Arm II: Patients receive oral high γ-tocopherol vitamin E supplementation once daily for 1 week.
- Arm III: Patients receive oral high γ-tocopherol vitamin E supplementation once daily for 2 weeks.
Blood, urine, and tissue samples are collected periodically and analyzed for oxidative/nitrosative stress and other markers (i.e., F2-isoprostane, 8-OHdG, 3-nitrotyrosine, prostaglandin E2, C-reactive protein, and PSA), biomarkers in prostate tumors and nontumorous tissues (i.e., 8-OHdG, 3-nitrotyrosine, and cyclooxygenase-2) by IHC, and pharmacokinetics by high-performance liquid chromatography.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •DISEASE CHARACTERISTICS:
- •Meets one of the following criteria:
- •Abnormal digital rectal examination or abnormal prostate specific antigen (> 4.0 ng/mL)
- •Obstructing prostate
- •Biopsy-proven prostate cancer
- •Scheduled to undergo prostate surgery (i.e., transurethral prostatectomy or prostatectomy)
- •PATIENT CHARACTERISTICS:
- •No uncontrolled diabetes, uncontrolled blood pressure, chronic congestive heart failure, or history of renal insufficiency
- •No personal or family history of a bleeding disorder
- •No known history of problems absorbing dietary fats (e.g., Crohn's disease, cystic fibrosis)
- •PRIOR CONCURRENT THERAPY:
- •More than 2 weeks since prior NSAIDs or corticosteroids
- •No concurrent supplementation of vitamin E (a multivitamin containing ≤ 60 IU of vitamin E is allowed)
- •No concurrent colestipol or orlistat
- •No concurrent warfarin or dicumarol
Exclusion Criteria
- Not provided
Arms & Interventions
Arm I
Patients receive no supplementation.
Intervention: sham intervention (Procedure)
Arm II
Patients receive oral high γ-tocopherol vitamin E supplementation once daily for 1 week.
Intervention: vitamin E (Dietary Supplement)
Arm III
Patients receive oral high γ-tocopherol vitamin E supplementation once daily for 2 weeks.
Intervention: vitamin E (Dietary Supplement)
Outcomes
Primary Outcomes
Effect of tocopherol supplementation on plasma and urine levels of α-, γ-, and δ-tocopherols, PSA, and prostaglandin E2
Time Frame: 4 years
Oxidative stress and nitrosative stress as assessed by plasma levels of F2-isoprostane, C-reactive protein, and 3-nitrotyrosine as well as urinary levels of 8-hydroxy-2-deoxyguanosine (8-OHdG)
Time Frame: 4 years
Levels of α-, γ-, and δ-tocopherols in prostate tissues and cell proliferation, apoptosis, cyclooxygenase-2, 8-OHdG, and 3-nitropyrosine levels as assessed by IHC
Time Frame: 4 years
Secondary Outcomes
No secondary outcomes reported