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.项目总结/摘要 本申请用于CA 098286（一种多中心、双盲、随机、安慰剂）的更新 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，这些数据表明，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 受试者在进入研究前4个月内至少切除了一个大肠腺瘤， 结肠镜检查显示结直肠粘膜，肠内无已知息肉。受试者 排除研究药物的毒性风险（例如，近期有肾结石病史）， 可能需要研究治疗（例如骨质疏松症）。参加者同意避免参加研究 试验外的特工合适的受试者以2 × 2析因方式随机分配至碳酸钙组 (1200 mg钙/天）、维生素D（1000 IU/天）、两种药物或安慰剂。我们为女性提供以下选择 被随机分配到单用钙或钙加维生素D组。结肠镜随访发生在3 资格考试后5年或5年，由每位受试者的胃肠病学家计划。如安全 在基线和治疗期间，将获得血清钙、肌酐和25-（OH）维生素D水平。 治疗期。该研究的主要终点是随访时的一个或多个肠肿瘤性息肉- 对晚期病变的影响评估将纳入次要分析。在保守 关于事件发生率和研究实施的假设，我们将有超过89%的把握度检测20%的 与安慰剂相比，维生素D可减少腺瘤复发，85%的把握度可检测到维生素D可减少腺瘤复发25%。 钙加维生素D与单纯钙治疗的复发率比较。其他分析也将有良好的统计 动力. 在资助的前5年，招生几乎完全按照计划进行;我们将 在2007年11月30日达到或超过我们的目标入组人数。到目前为止，实验对象表现出了出色的 遵守研究程序和药物，很少有受试者不得不停止随机化治疗 由于不良事件（例如肾结石）或需要研究药物（例如骨质疏松症）。我们现在 申请资金以完成所有2,200名随机受试者的计划治疗和随访， 第一次疗效分析，并实施治疗后随访。7.项目叙述 结直肠癌是美国最常见的癌症之一。 在临床试验中证实，补充钙或维生素D可以减少 结直肠腺瘤的风险，良性肿瘤，如果留在原位，可能演变成癌症。 研究药物是安全的，已经广泛使用，因此如果它们能有效地干扰 在大肠致癌作用中，公共卫生意义可能是 相当可观