Identification of 24-Hydroxylase Polymorphisms and Splicing Variants That Modulate Vitamin D Oxidative Metabolism and Serum Pharmacokinetics in Patients With Colorectal Cancer on Cholecalciferol Therapy

Roswell Park Cancer Institute1 个研究点分布在 1 个国家目标入组 50 人开始时间: 2007年8月1日最近更新: 2017年4月4日

适应症

干预措施

试验速览

阶段: 不适用
状态: 已完成
发起方: Roswell Park Cancer Institute
入组人数: 50
试验地点: 1
主要终点: Effect of CYP24 SNPs on serum vitamin D3 metabolites and PTH levels during cholecalciferol treatment

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

RATIONALE: Studying samples of blood from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer.

PURPOSE: This clinical trial is studying changes in DNA that affect vitamin D metabolism in patients with colorectal cancer receiving vitamin D supplements.

详细描述

OBJECTIVES:

To identify CYP24 single nucleotide polymorphisms (SNPs) using peripheral blood mononuclear cell genomic DNA from patients with colorectal cancer receiving cholecalciferol supplementation.
To evaluate the effects of these CYP24 SNPs on baseline serum vitamin D_3 metabolites (25-D_3, 24,25-D_3, and 1,25-D_3), and parathyroid hormone levels (PTH).
To evaluate the effects of these CYP24 SNPs on serum vitamin D_3 metabolites and PTH levels during cholecalciferol treatment.
To examine CYP24 splicing, protein expression, and enzyme activity at baseline and during cholecalciferol treatment.
To determine the relationship, if any, between serum cholecalciferol pharmacokinetic parameters and CYP24 SNPs, splicing variants, and enzyme activity.

OUTLINE: Patients receive oral cholecalciferol 2000 IU once daily for 1 year. Patients without response to vitamin D supplementation (serum 25-D_3 level < 32 ng/mL) by 6 months will have their cholecalciferol dose increased to 4000 IU once daily.

Blood is collected at baseline and on days 14, 30, 60, 90, 180, 270, and 360. Peripheral blood mononuclear cells for CYP24 genotyping, protein expression, enzyme activity, and splicing variants are analyzed by polymerase chain reaction (PCR), western blot, high performance liquid chromatography, and reverse transcriptase PCR, respectively. Serum is analyzed for vitamin D_3 metabolite levels (by radioimmunoassay), calcium (to monitor for hypercalcemia), and parathyroid hormone assays (to measure vitamin D effect).

研究设计

研究类型: Interventional
分配方式: Na
干预模型: Single Group
主要目的: Supportive Care
盲法: None

入排标准

年龄范围: 18 Years 至 120 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•DISEASE CHARACTERISTICS:
•Prior or current documented diagnosis of colorectal cancer
•All stages
•25OH-D3 level < 50 ng/mL
•PATIENT CHARACTERISTICS:
•ECOG performance status 0-2
•Life expectancy > 6 months
•Serum creatinine < 2.0 mg/dL
•Serum bilirubin < 2.0 mg/dL
•No prior or current hypercalcemia (defined as albumin corrected serum calcium < 10.2 mg/dL)
•No known contraindication for vitamin D supplementation
•No genitourinary stones within the past 5 years
•No severe comorbid conditions such as uncompensated heart failure or active infection
•PRIOR CONCURRENT THERAPY:
•No supplemental vitamin D beyond what is provided through the study
•At least 2 months since prior vitamin D supplementation exceeding 800 International Units (IU)
•Nondietary vitamin D supplements should not have exceeded 800 IU/day within the past 2 months

排除标准

未提供