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 和钙在大肠中发挥抗肿瘤作用。 然而，需要临床试验的证据来阐明这两种药物的协同和独立的化疗预防作用。肠道肿瘤性息肉（腺瘤）被认为是癌前病变，也是化学预防研究的有效终点。 我们的研究联盟已经利用这些终点成功地进行了几项化学预防试验，在这次重新提交中，我们提出了一项多中心随机、双盲、部分析因试验，探讨碳酸钙和维生素 D 在预防大肠肿瘤性息肉复发方面的功效。 该研究将涉及北美10个临床中心、一个病理中心和一个协调中心。 每位受试者在进入研究前 4 个月内至少切除一处大肠腺瘤，并通过结肠镜完整观察结直肠粘膜，并且肠道内没有残留已知的息肉。参与者将同意避免在试验之外服用研究药物，并且最初将在 3 个月的安慰剂磨合期内进行观察，在此期间将评估对研究的适合性。 合适的受试者将以 2 x 2 阶乘方式随机分配至碳酸钙（1200 毫克钙/天）、维生素 D（1000 IU/天）、两种药物或安慰剂。由于许多女性可能拒绝放弃钙补充剂，因此我们将为女性提供随机选择，即单独服用钙剂或服用钙剂加维生素 D。根据每位受试者的医生的计划，结肠镜随访将在资格考试后 3 年或 5 年进行。 作为安全措施，将在基线以及随机分组后 1 年和 3 年获取血清钙、肌酐和 25-(OH) 维生素 D 水平。 我们预计招募约 2456 名参与者，总共 1966 名随机受试者。 根据关于事件发生率和研究实施的保守假设，我们将有超过 89% 的功效检测到维生素 D 与安慰剂相比，腺瘤复发率降低 20%，并且有 85% 的功效检测到钙加维生素 D 与单独使用钙剂相比，腺瘤复发率降低 25%。