NCT00550563

DNA Changes That Affect Vitamin D Metabolism in Patients With Colorectal Cancer Receiving Vitamin D Supplements

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

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 50 (actual)
• Sponsor: Roswell Park Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years – 120 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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).

Conditions

• Colorectal Cancer

Interventions

Type	Name	Description
DIETARY_SUPPLEMENT	cholecalciferol	Oral
GENETIC	polymerase chain reaction	companion study
GENETIC	polymorphism analysis	companion study
GENETIC	protein expression analysis	companion study
GENETIC	reverse transcriptase-polymerase chain reaction	companion study
GENETIC	western blotting	companion study
OTHER	high performance liquid chromatography	companion study
OTHER	laboratory biomarker analysis	companion study
OTHER	pharmacological study	companion study
PROCEDURE	adjuvant therapy	Additional therapy
PROCEDURE	immunoscintigraphy	additional testing

Timeline

• Start date: 2007-08-01
• Primary completion: 2009-04-01
• Completion: 2010-07-01
• First posted: 2007-10-30
• Last updated: 2017-04-04

Locations

1 site across 1 country: United States