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 此应用程序用于CA098286的续订，这是一种多中心，双盲，随机，安慰剂 补充维生素D和/或钙的对照试验预防结直肠腺瘤。 该研究以广泛的流行病学和实验数据为基础，表明维生素D和 钙在大肠中发挥抗肿瘤作用。 该研究涉及美国的11个临床中心，一个病理中心和一个协调中心。每个 受试者在研究入学前的4个月中至少要去除一个大肠腺瘤，完整 结肠直肠粘膜的结肠镜检查和肠道中没有已知的息肉。受试者在 排除研究剂的毒性风险（例如，肾结石的近期历史）被排除在外， 可能需要研究治疗（例如骨质疏松症）。参与者同意避免学习 审判外的代理商。合适的受试者以2 x 2阶乘方式随机分配给碳酸钙 （1200毫克钙/天），维生素D（1000 IU/天），包括药剂或安慰剂。我们为女性提供选择 被随机化为单独的钙或钙加维生素D。结肠镜随访发生在任何一个3 根据每个受试者的胃肠病学家计划，在合格考试后数年或5年。作为安全 措施，血清钙，肌酐和25-（OH）维生素D水平将在基线时以及在 治疗期。该研究的主要终点是肠道上的一个或多个肿瘤息肉。 向上;评估晚期病变的影响将包括在次级分析中。在保守派之下 关于事件率和研究行为的假设，我们将拥有超过89％的功率来检测20％ 维生素D与安慰剂相比，腺瘤复发的降低，并降低了85％的功率，可检测25％的降低 单独使用钙加维生素D与钙复发。其他分析也将具有良好的统计 力量。 在资金的前5年中，入学人数几乎按时间表进行；我们将 在2007年11月30日满足或超过我们的目标入学率。迄今为止，受试者表现出色 遵守研究程序和药物，很少有受试者不得不停止随机治疗 由于不良事件（例如Kidney Stones）或对研究剂的需求（例如骨质疏松症）。我们现在 要求资金完成所有2200名随机受试者的计划治疗和随访，准备 第一个功效分析并实施后续后续行动。 7。项目叙述 大肠癌是美国最常见的癌症之一，这项研究的目的是 在临床试验中确认补充钙或维生素D可以减少 结直肠腺瘤，良性肿瘤，如果留在原位，可以演变成癌症。 研究代理人是安全的，并且已经广泛使用，因此，如果它们有效干扰 随着大肠中的致癌作用，公共卫生的意义可能是 重大的。