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

Not Applicable

Completed

• Conditions: Colorectal Cancer
• Interventions: Dietary Supplement: cholecalciferol; Genetic: polymerase chain reaction; Genetic: polymorphism analysis; Genetic: protein expression analysis; Genetic: reverse transcriptase-polymerase chain reaction; Genetic: western blotting; Other: high performance liquid chromatography; Other: laboratory biomarker analysis; Other: pharmacological study; Procedure: adjuvant therapy; Procedure: immunoscintigraphy

• Registration Number: NCT00550563
• Lead Sponsor: Roswell Park Cancer Institute

Brief 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).

Study Timeline

• Study Start: 2007-08
• Study First Submitted: 2007-10-25
• Study First Submitted QC: 2007-10-25
• Study First Posted: 2007-10-30
• Primary Completion: 2009-04
• Study Completion: 2010-07
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-31
• Last Update Posted: 2017-04-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Oral Cholecalciferol	western blotting	Patients receive oral cholecalciferol 2000 IU once daily for 1 year
Oral Cholecalciferol	polymorphism analysis	Patients receive oral cholecalciferol 2000 IU once daily for 1 year
Oral Cholecalciferol	adjuvant therapy	Patients receive oral cholecalciferol 2000 IU once daily for 1 year
Oral Cholecalciferol	cholecalciferol	Patients receive oral cholecalciferol 2000 IU once daily for 1 year
Oral Cholecalciferol	polymerase chain reaction	Patients receive oral cholecalciferol 2000 IU once daily for 1 year
Oral Cholecalciferol	protein expression analysis	Patients receive oral cholecalciferol 2000 IU once daily for 1 year
Oral Cholecalciferol	reverse transcriptase-polymerase chain reaction	Patients receive oral cholecalciferol 2000 IU once daily for 1 year
Oral Cholecalciferol	laboratory biomarker analysis	Patients receive oral cholecalciferol 2000 IU once daily for 1 year
Oral Cholecalciferol	pharmacological study	Patients receive oral cholecalciferol 2000 IU once daily for 1 year
Oral Cholecalciferol	high performance liquid chromatography	Patients receive oral cholecalciferol 2000 IU once daily for 1 year
Oral Cholecalciferol	immunoscintigraphy	Patients receive oral cholecalciferol 2000 IU once daily for 1 year

Primary Outcome Measures

Name	Time	Method
Identification of CYP24 single nucleotide polymorphisms (SNPs)	Baseline, days 14, 30, 60, 90, 180, 270, 360
Effect of CYP24 SNPs on serum vitamin D3 metabolites and PTH levels during cholecalciferol treatment	Baseline, days 14, 30, 60, 90, 180, 270, 360
CYP24 splicing, protein expression, and enzyme activity at baseline and during cholecalciferol treatment	Baseline, days 14, 30, 60, 90, 180, 270, 360
Effect of CYP24 SNPs on baseline serum vitamin D3 metabolites (25-D3, 24,25-D3, and 1,25-D3), and parathyroid hormone levels (PTH)	At baseline
Relationship between serum cholecalciferol pharmacokinetic parameters and CYP24 SNPs, splicing variants, and enzyme activity	Baseline, days 14, 30, 60, 90, 180, 270, 360

Trial Locations

Locations (1)

Roswell Park Cancer Institute; 🇺🇸 Buffalo, New York, United States