Colorectal Chemoprevention with Calcium and Vitamin D

使用钙和维生素 D 进行结直肠化学预防

• 批准号: 8305757
• 负责人: John Anthony Baron
• 金额: $ 322.67万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-17 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8305757
• 关键词: Adverse event; Aftercare; Benign; Calcium; Calcium Carbonate; Caliber; Chemoprevention; Cholecalciferol; Clinical; Clinical Trials; Colonoscopy; Colorectal; Colorectal Adenoma; Colorectal Cancer; Creatinine; Data; Data Files; Double-Blind Method; Dysplasia; Effectiveness; Enrollment; Epidemiology; Event; Funding; Gastroenterologist; Genetic Polymorphism; Histology; Hospitalization; Imagery; Individual; Intestines; Kidney Calculi; Large Intestine; Left; Lesion; Malignant Neoplasms; Measures; Mucous Membrane; Neoplastic Polyp; Osteoporosis; Participant; Pathology; Patients; Phase; Placebos; Polyps; Prevention; Procedures; Public Health; Qualifying; Questionnaires; Randomized; Reading; Receptor Gene; Recording of previous events; Recurrence; Risk; Safety; Schedule; Serum; Supplementation; Toxic effect; Villous; Vitamin D; Vitamin D3 Receptor; Woman; Work; abstracting; adenoma; carcinogenesis; double-blind placebo controlled trial; follow-up; meetings; neoplastic; pre-clinical; prevent; randomized placebo controlled trial; treatment duration; treatment planning; tumor

6. Project Summary/Abstract This application is for the renewal of CA098286, a multicentered, double-blind, randomized, placebo controlled trial of supplementation with vitamin D and/or calcium for the prevention of colorectal adenomas. The study builds on extensive epidemiological and experimental data indicating that both vitamin D and calcium exert anti-neoplastic effects in the large bowel. The study involves 11 clinical centers in the US, a pathology center and a coordinating center. Each subject has at least one large bowel adenoma removed in the 4 months prior to study entry, with complete colonoscopic visualization of the colorectal mucosa and no known polyps remaining in the bowel. Subjects at risk for toxicity from study agents (e.g. with a recent history of kidney stones) are excluded, as are those with a likely need for the study treatments (e.g. with osteoporosis). Participants agree to avoid taking study agents outside the trial. Suitable subjects are randomized in a 2 x 2 factorial manner to calcium carbonate (1200 mg calcium/day), vitamin D (1000 IU/day), both agents, or placebo. We offer women the choice of being randomized to calcium alone or calcium plus vitamin D. Colonoscopic follow-up occurs at either 3 years or 5 years after the qualifying exam, as planned by each subject's gastroenterologist. As safety measures, serum calcium, creatinine and 25-(OH) vitamin D levels will be obtained at baseline, and during the treatment period. The main endpoint of the study is one or more neoplastic polyps of the bowel on follow- up; assessment of effects for advanced lesions will be included in secondary analyses. Under conservative assumptions regarding event rates and study conduct, we will have greater than 89% power to detect a 20% reduction in adenoma recurrence with vitamin D versus placebo, and 85% power to detect a 25% reduction in recurrence with calcium plus vitamin D versus calcium alone. Other analyses will also have good statistical power. During the first 5 years of funding, enrollment has proceeded almost exactly according to schedule; we will meet or exceed our target enrollment on November 30, 2007. To date, subjects have shown excellent compliance with study procedures and agents, and few subjects have had to stop randomized treatment because of adverse events (e.g.kidney stones) or a need for the study agents (e.g. osteoporosis). We now request funds to complete the planned treatment and follow-up for all 2,200 randomized subjects, prepare for the first efficacy analyses, and implement a post-treatment follow-up. 7. Project Narrative Colorectal cancer is one of the most common cancers in the U.S. This study aims to confirm in a clinical trial that supplementation with calcium or vitamin D can reduce the risk of colorectal adenomas, benign tumors that can evolve into cancer if left in place. The study agents are safe and already widely used, so if they are effective in interfering with carcinogenesis in the large bowel, the public health significance could be substantial.

6.项目摘要/摘要 本申请是为多中心、双盲、随机、安慰剂CA098286续期的 补充维生素D和/或钙预防结直肠腺瘤的对照试验 这项研究建立在广泛的流行病学和实验数据的基础上，表明维生素D和 钙在大肠中发挥抗肿瘤作用。 这项研究涉及美国的11个临床中心，一个病理中心和一个协调中心。每个人 受试者在进入研究前的4个月内至少切除了一个大肠腺瘤，并完成 结肠镜下可见大肠粘膜，肠内无息肉残留。科目： 研究试剂(例如，最近有肾结石病史)的毒性风险被排除在外，那些具有 可能需要进行研究治疗(例如骨质疏松症)。参与者同意避免参加学习 庭审外的探员。合适的受试者以2×2因子的方式随机服用碳酸钙 (1200毫克钙/天)，维生素D(1000国际单位/天)，两种药物，或安慰剂。我们为女性提供以下选择 随机接受单独钙剂或钙剂加维生素D的治疗，结肠镜检查的随访时间为 按照每个受试者的胃肠病专家的计划，在合格考试后的五年或五年内。作为安全 测量时，将在基线和期间获得血钙、肌酐和25-(OH)维生素D水平。 治疗周期。研究的主要终点是一个或多个肠道肿瘤性息肉。 对晚期病变的影响评估将包括在二次分析中。在保守之下 关于事件发生率和研究进行的假设，我们将有超过89%的能力检测20% 与安慰剂相比，维生素D减少腺瘤复发，85%的力量检测到25%的 钙剂加维生素D与单独使用钙剂相比复发。其他分析也会有很好的统计数据 权力。 在资助的前5年，招生几乎完全按计划进行；我们将 在2007年11月30日达到或超过我们的目标注册人数。到目前为止，受试者表现得非常出色 遵守研究程序和药物，很少有受试者不得不停止随机治疗 因为不良事件(例如肾结石)或需要研究药物(例如骨质疏松症)。我们现在 申请资金完成所有2,200名随机受试者的计划治疗和随访，为 首先进行疗效分析，并实施治疗后的随访。7.项目叙事 结直肠癌是美国最常见的癌症之一。这项研究旨在 在一项临床试验中证实，补充钙或维生素D可以减少 结直肠腺瘤的风险，良性肿瘤如果留在原地可能演变为癌症。 研究试剂是安全的，而且已经被广泛使用，所以如果它们在干预方面有效 由于大肠癌变，对公共卫生的意义可能是 相当可观。