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

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ClinicalTrials.gov Identifier: NCT00550563
Recruitment Status : Completed
First Posted : October 30, 2007
Last Update Posted : April 4, 2017
Sponsor:
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Colorectal Cancer 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 Not Applicable

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: 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
Study Start Date : August 2007
Actual Primary Completion Date : April 2009
Actual Study Completion Date : July 2010

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Oral Cholecalciferol
Patients receive oral cholecalciferol 2000 IU once daily for 1 year
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




Primary Outcome Measures :
  1. Identification of CYP24 single nucleotide polymorphisms (SNPs) [ Time Frame: Baseline, days 14, 30, 60, 90, 180, 270, 360 ]
  2. Effect of CYP24 SNPs on baseline serum vitamin D3 metabolites (25-D3, 24,25-D3, and 1,25-D3), and parathyroid hormone levels (PTH) [ Time Frame: At baseline ]
  3. Effect of CYP24 SNPs on serum vitamin D3 metabolites and PTH levels during cholecalciferol treatment [ Time Frame: Baseline, days 14, 30, 60, 90, 180, 270, 360 ]
  4. CYP24 splicing, protein expression, and enzyme activity at baseline and during cholecalciferol treatment [ Time Frame: Baseline, days 14, 30, 60, 90, 180, 270, 360 ]
  5. Relationship between serum cholecalciferol pharmacokinetic parameters and CYP24 SNPs, splicing variants, and enzyme activity [ Time Frame: Baseline, days 14, 30, 60, 90, 180, 270, 360 ]


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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00550563


Locations
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
Sponsors and Collaborators
Roswell Park Cancer Institute
Investigators
Principal Investigator: Marwan Fakih, MD Roswell Park Cancer Institute

Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT00550563     History of Changes
Other Study ID Numbers: I 99207
RPCI-I-99207
First Posted: October 30, 2007    Key Record Dates
Last Update Posted: April 4, 2017
Last Verified: March 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Roswell Park Cancer Institute:
recurrent colon cancer
stage I colon cancer
stage II colon cancer
stage III colon cancer
stage IV colon cancer
recurrent rectal cancer
stage I rectal cancer
stage II rectal cancer
stage III rectal cancer
stage IV rectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Vitamins
Vitamin D
Cholecalciferol
Micronutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents