A Pilot Metabolomic Study of the Effects of Vitamin D and Calcium Supplementation

维生素 D 和钙补充剂影响的初步代谢组学研究

基本信息

批准号：
8637394
负责人：
John Anthony Baron
金额：
$ 16.33万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-09-17 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8637394
关键词：
Affect Androgen Receptor Antineoplastic Agents Bile Acids Bioinformatics Biological Markers Biometry Biopsy Calcium Catabolism Cataloging Catalogs Cell Cycle Characteristics Chemoprevention Chemopreventive Agent Cholecalciferol Chronic Disease Clinical Clinical Data Clinical Investigator Clinical Trials Collaborations Colorectal Colorectal Adenoma Colorectal Cancer Colorectal Neoplasms Controlled Clinical Trials Correlation Studies Data Databases Development Diet Dissociation Double-Blind Method Estrogen Receptors Fourier Transform Future Genes Genetic Variation Genome Goals Growth Factor Human Human Genome Individual Inflammation Intervention Trial Investigation Ions Laboratories Lead Life Style Lipids Liquid Chromatography Maps Mass Spectrum Analysis Measures Metabolic Metabolic Pathway Methodology Methods Mucous Membrane Myocardial Ischemia North Carolina Parents Participant Pathway interactions Patients Phenotype Pilot Projects Placebo Control Placebos Plasma Prevention Randomized Recurrence Reducing Agents Research Personnel Resolution Risk Risk-Benefit Assessment Sample Size Sampling Signal Transduction Spectrum Analysis Supplementation Testing Tissues Universities Variant Visit Vitamin D adenoma carcinogenesis disorder risk efficacy testing follow-up immune function innovation metabolomics novel pre-clinical prevent rectal tool

项目摘要

This collaborative proposal between the University of North Carolina ¿ Chapel Hill and Emory University is an adjunct pilot metabolomic study to an ongoing multi-center, randomized, double-blind, placebo-controlled, modified 2 x 2 factorial chemoprevention clinical trial (R01 CA98286; PI: J. Baron) (n = 2,259) that is testing the efficacy of supplemental vitamin D3 (1,000 IU daily) and calcium (1,200 mg elemental calcium daily), alone and in combination vs. placebo over 3 ¿ 5 years in preventing sporadic colorectal adenoma recurrence (the ¿parent study¿). The objective of this proposal is to establish a new interactive collaboration between clinical researchers in the parent study and metabolomics experts, and to incorporate a novel high-resolution metabolomics approach into the parent study to better understand the independent and synergistic antineoplastic actions and other effects of vitamin D and calcium in humans. Our innovative approach utilizes high-resolution mass spectrometry to measure >20,000 metabolites, and provides a unique workflow using false discovery rates (FDR) to prioritize metabolites for subsequent study, correlation analysis to enhance identification of relevant metabolic modules associated with these prioritized metabolites, pathway mapping using available online tools to identify relevant metabolic pathways, and post-hoc application of ion dissociation (MS/MS) spectroscopy to representative metabolites to confirm pathway identification. In the pilot study we will obtain preliminary data on the effects of supplementation with vitamin D and/or calcium on individual metabolites and metabolic pathways in a sub-set of participants (n = 120) with baseline and follow-up biopsies of normal-appearing rectal mucosa. The preliminary results obtained from this pilot study will lead to larger, full-scale, metabolomic investigations to elucidate 1) the individual and combined effects of vitamin D and calcium on metabolomic pathways in humans (thus providing a more comprehensive assessment of the benefits and risks of these heavily promoted agents as supplements), 2) whether these metabolomic changes correlate with genetic variation and systemic and tissue-specific biomarkers in humans (and thus their direct relevance to the chemoprevention of colorectal neoplasms), and 3) whether the metabolomic changes predict the occurrence of sporadic colorectal adenomas in humans, thus paving the way for the development of treatable biomarkers of risk for colorectal neoplasia that are analogous to lipid profiles for the prevention of ischemic heart disease. Elucidating the effects of vitamin D and/or calcium supplementation on individual metabolites and metabolomic pathways may inform the potential use of these chemopreventive agents for preventing colorectal neoplasms, and, possibly, other chronic diseases.

北卡罗来纳大学（Chapel Hill）与埃默里大学（Emory University）之间的这项合作提议是一项辅助试验代谢组学研究，对正在进行的多中心，随机，双盲，安慰剂对照，修改2 x 2 fortorial化学疗程临床试验（R01 CA98286; PI：J. BARON; PI：N = 2,259）（每天1,000 IU）和钙（每天1,200毫克元素钙），单独使用，组合与安慰剂相比3年以上，可预防零星的结直肠腺瘤复发（父母研究）。该建议的目的是在父母研究中建立临床研究人员与代谢组学专家之间的新互动合作，并将一种新型的高分辨率代谢组学方法纳入父母研究中，以更好地了解人类中维生素D和钙的独立和有效的抗肿瘤作用和其他影响。 Our innovative approach utilizes high-resolution mass spectrometry to measure >20,000 metabolites, and provides a unique workflow using false discovery rates (FDR) to prioritize metabolites for subsequent study, correlation analysis to enhance identification of relevant metabolites associated with these prioritized metabolites, pathway mapping using available online tools to identify relevant metabolic pathways, and post-hoc application of ion dissociation (MS/MS)光谱法代表代谢物以确认途径鉴定。在试点研究中，我们将获取有关补充维生素D和/或钙对参与者的单个代谢产物和代谢途径的效果的初步数据（n = 120），其基线和正常现代直肠粘膜的随访活检。从这项试验研究中获得的初步结果将导致更大的，全尺度的代谢组合研究以阐明1）1）维生素D和钙对人类代谢途径的个体和联合影响，从而更全面地评估了这些因素和系统，这些剂量和风险与这些属性和统一的依赖性相关，2）是否会改变属性，2）2）是否会改变属性，2）2） biomarkers in humans (and thus their direct relevance to the chemoprevention of colorectal neoplasms), and 3) whether the metabolomic changes predict the occurrence of sporadic colorectal adenomas in Humans, thus pasting the way for the development of treatable biomarkers of risk for colorectal neoplasia that are analogous to lipid profiles for the prevention of ischemic heart disease.阐明维生素D和/或钙补充对单个代谢产物和代谢组途径的影响可能会为这些化学预防剂的潜在用途提供了预防结肠直肠肿瘤的使用，以及其他可能的其他慢性疾病。