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: 6929876
• 负责人: John Anthony Baron
• 金额: $ 367.45万
• 依托单位: DARTMOUTH COLLEGE
• 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 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6929876
• 关键词: adenomatous polyps; biopsy; calcium carbonate; chemoprevention; clinical research; clinical trials; colorectal neoplasms; combination chemotherapy; dietary supplements; endoscopy; gastrointestinal imaging /visualization; genetic polymorphism; human subject; human therapy evaluation; longitudinal human study; neoplasm /cancer chemotherapy; nutrition aspect of cancer; nutrition related tag; patient oriented research; questionnaires; statistics /biometry; vitamin D; vitamin D receptors; vitamin therapy

DESCRIPTION (provided by applicant): Epidemiological and experimental data indicate that both vitamin D and calcium exert anti-neoplastic effects in the large bowel. However, evidence from clinical trials is required to clarify the synergistic and independent chemo preventive effects of these two agents. Neoplastic polyps (adenomas) of the bowel are recognized pre-malignant lesions and effective endpoints for chemoprevention studies. Our research consortium has successfully conducted several chemoprevention trials using these endpoints, and in this resubmission, we propose a multi-centered randomized, double blind, partial factorial trial of the efficacy of calcium carbonate and vitamin D in preventing the recurrence of neoplastic polyps of the large bowel. The study will involve 10 clinical centers in North America, a pathology center and a coordinating center. Each subject will have had 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. Participants will agree to avoid taking study agents outside the trial and will initially be observed in a 3- month placebo run-in period during which suitability for the study will be assessed. Suitable subjects will be randomized in a 2 x 2 factorial manner to calcium carbonate (1200 mg calcium/day), vitamin D (1000 IU/day), both agents, or placebo. Since many women may decline to forgo calcium supplementation, we will offer women the choice of being randomized to calcium alone or calcium plus vitamin D. Colonoscopic follow-up will occur at either 3 years or 5 years after the qualifying exam, as planned by each subject's physician. As safety measures, serum calcium, creatinine and 25-(OH) vitamin D levels will be obtained at baseline, and 1 year and 3 years after randomization. We anticipate enrolling about 2456 participants to reach a total of 1966 randomized subjects. Under conservative assumptions regarding event rates and study conduct, we will have greater than 89 percent power to detect a 20 percent reduction in adenoma recurrence with vitamin D versus placebo, and 85 percent power to detect a 25 percent reduction in recurrence with calcium plus vitamin D versus calcium alone.

描述（由申请人提供）：流行病学和实验数据表明，维生素D和钙都在大肠中发挥抗肿瘤作用。 但是，需要进行临床试验的证据来阐明这两种药物的协同和独立的化学预防作用。肠道的肿瘤息肉（腺瘤）是公认的恶性病变和化学预防研究的有效终点。 我们的研究联盟已成功地使用了这些终点进行了几项化学预防试验，在此重新提交中，我们提出了一项以碳酸钙和维生素D在防止大肠中碳酸盐再现的碳酸钙和维生素D疗效的多中心的随机，双盲，部分阶级试验。 该研究将涉及北美的10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四个月中至少要清除一个大肠腺瘤，并完全结肠镜下可视化结直肠粘膜，肠道中没有剩下的已知息肉。参与者将同意避免将研究人员带到试验外，并在3个月的安慰剂磨合期中被观察到，在此期间将评估该研究的适用性。 合适的受试者将以2 x 2的阶乘方式随机分配给碳酸钙（1200 mg钙/天），维生素D（1000 IU/天），包括药剂或安慰剂。由于许多女性可能拒绝放弃钙补充，因此我们将为妇女选择单独使用钙或钙加维生素D。结肠镜检查的随访将发生在合格检查后的3年或5年后，按照每个受试者的医生计划。 作为安全措施，将在基线时以及随机分组后的1年零3年中获得血清钙，肌酐和25-（OH）维生素D水平。 我们预计将招收约2456名参与者将达到1966名随机受试者。 在关于事件率和研究行为的保守假设下，我们将拥有超过89％的功率，以检测维生素D与安慰剂相对于安慰剂的腺瘤复发降低20％，以及85％的功率可检测钙的复发降低25％，而钙加上维生素D相对于钙的复发率降低了25％。