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: 7890574
• 负责人: John Anthony Baron
• 金额: $ 390.02万
• 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/7890574
• 关键词: Adverse event; Aftercare; Benign; Calcium; Calcium Carbonate; Calculi; 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 assessment; follow-up; meetings; neoplastic; pre-clinical; prevent; randomized placebo controlled trial; treatment duration; treatment planning; tumor

DESCRIPTION (provided by applicant): 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 followup; 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.

描述(申请人提供)：本申请是为了续签CA098286，这是一项多中心、双盲、随机、安慰剂对照试验，旨在补充维生素D和/或钙以预防结直肠腺瘤。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和钙在大肠中都具有抗肿瘤作用。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，并在结肠镜下完整地看到了大肠粘膜，肠内没有已知的息肉。有研究试剂毒性风险的受试者(例如，最近有肾结石病史)被排除在外，那些可能需要研究治疗的受试者(例如，骨质疏松症)也被排除在外。参与者同意避免将研究代理带到试验之外。合适的受试者按2×2因素随机分为碳酸钙(每天1200毫克钙)、维生素D(每天1000IU)、两种药物或安慰剂。我们为女性提供了两种选择，一种是随机接受单独补钙，另一种是补钙加维生素D。按照每个受试者的胃肠病专家的计划，结肠镜检查的随访时间是在合格检查后的3年或5年。作为安全措施，在基线和治疗期间将获得血钙、肌酐和25-(OH)维生素D水平。研究的主要终点是随访的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。在事件发生率和研究进行的保守假设下，与安慰剂相比，服用维生素D的患者检测到腺瘤复发率降低20%的能力超过%，与单独服用钙剂的患者相比，服用维生素D+钙的患者复发率降低25%的能力超过85%。其他分析也将具有很好的统计能力。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招生。到目前为止，受试者对研究程序和药物的依从性很好，很少有受试者因为不良事件(如肾结石)或需要研究药物(如骨质疏松症)而不得不停止随机治疗。我们现在申请资金，以完成对所有2200名随机受试者的计划治疗和随访，准备第一次疗效分析，并实施治疗后随访。