Clinical Trial of Vitamin D3 to Reduce Cancer Risk in Postmenopausal Women

维生素 D3 降低绝经后妇女癌症风险的临床试验

• 批准号: 8026866
• 负责人: JOAN LAPPE
• 金额: $ 76.2万
• 依托单位: CREIGHTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-01 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8026866
• 关键词: 1,25 (OH) vitamin D; 25-hydroxyvitamin D; 9 year old; Address; Adherence; Adverse event; Age-Years; Animals; Bladder; Breast; Calcium; Cardiovascular Diseases; Cell Differentiation process; Cells; Cessation of life; Chemopreventive Agent; Cholecalciferol; Clinical Trials; Clinical Trials Design; Cohort Studies; Colon; Colon Carcinoma; Colonic Adenoma; County; Data; Degenerative polyarthritis; Diabetes Mellitus; Dietary Intervention; Dietary intake; Dihydroxycholecalciferols; Disease; Double-Blind Method; Enrollment; Epidemiologic Studies; Epidemiology; Esophagus; Foundations; Fracture; Future; Genetic Markers; Goals; Health; Health Policy; Height; Hypertension; In Vitro; Incidence; Intake; Intervention; Intervention Studies; Kidney; Leukocytes; Life; Link; Lung; Malignant Neoplasms; Malignant neoplasm of pancreas; Mediating; Medical; Methods; Mixed Function Oxygenases; Multiple Myeloma; Nebraska; Nested Case-Control Study; Non-Hodgkin' s Lymphoma; Nurses; Nutritional; Outcome; Outcome Study; Ovary; Pancreas; Paper; Participant; Patient Self-Report; Physical activity; Placebos; Population; Postmenopause; Prostate; Publishing; Radiation; Randomized; Randomized Clinical Trials; Randomized Controlled Clinical Trials; Receptor Activation; Recording of previous events; Rectum; Reporting; Research; Risk; Risk Factors; Rural; Sampling; Science; Serum; Source; Stimulus; Stomach; Strategic Planning; Study of serum; Sunlight; Supplementation; Testing; Time; Tissues; Upper Respiratory Infections; Uterus; Visceral; Visit; Vitamin D; Vitamin D Nutrition; Vitamin D3 Receptor; Vitamins; Weight; Woman; angiogenesis; animal data; autocrine; base; calcium intake; cancer diagnosis; cancer prevention; cancer risk; cancer type; chemical carcinogenesis; cohort; dimethylbenzanthracene; falls; follow-up; leukemia/lymphoma; malignant breast neoplasm; men; mortality; population based; prevent; primary outcome; randomized placebo controlled trial; response; social

DESCRIPTION (provided by applicant): An inverse correlation between cancer mortality rates and regional solar UV-B radiation exposure, a major source of vitamin D, has been found for cancers of the breast, colon, rectum, ovary; prostate, stomach, bladder, esophagus, kidney, lung, pancreas, and uterus, as well as non-Hodgkins lymphoma, and multiple myeloma. The anticancer effect of vitamin D is strongly supported by in vitro, animal, and epidemiological studies. Although a large body of evidence now links low vitamin D intake and low serum 25- hydroxyvitamin D (25OHD) to increased risk of various types of cancer, no reports were found of the effects of vitamin D status on all-cancer incidence. Furthermore, no randomized clinical trials have been reported that used a vitamin D intervention sufficient to raise serum 25OHD to optimum levels and that targeted a cancer outcome. A recent population-based study done by our group to determine the anti-fracture efficacy of calcium and vitamin D3 supplementation in healthy postmenopausal women demonstrated that vitamin D3 reduces all-cancer incidence. These findings need to be confirmed with a randomized controlled clinical trial designed with incidence of cancer as the primary outcome variable. In this application we propose to test whether increasing serum 25OHD to optimal levels, while maintaining adequate calcium intake, reduces the incidence of cancer in a population-based sample of postmenopausal women 60+ years of age. The Specific Aims are to: 1. Sample randomly the population of healthy independently-living postmenopausal women 60 years and older from 9 adjacent rural counties in Nebraska; 2. Enroll 2300 women into an intervention study, assign them randomly to 1 of 2 treatment groups: 1) vitamin D3 (2000 ID/d) and calcium (1200 mg/d), or 2) vitamin D3 placebo and calcium placebo, and to follow each subject for 4 years; 3. Collect and store white blood cells from every subject to test for genetic markers should the intervention be found effective in decreasing the incidence of cancer; 4. Determine the effect of supplementation with vitamin D3on incidence of all types of cancer combined; 5. Determine in a nested-case control study the association of serum 25OHD collected at randomization and at the end of year 1 of study with risk of cancer over 4 years. At each semiannual visit, the following will be assessed: medical and social history; adverse events; cancer diagnoses; and adherence to supplement/placebo. Annually, we will obtain height and weight and analyze serum 25OHD and1,25-dihydroxyvitamin D. At baseline and end of follow-up, we will assess dietary intake and physical activity. The proposed study addresses the goal of NCI's Strategic Plan to "eliminate the suffering and death due to cancer by 2015." It specifically addresses Strategic Objective 2, to "accelerate progress in cancer prevention." Positive findings from our proposed nutritional intervention study will result in an inexpensive, safe method of preventing cancer.

描述（由申请人提供）：已发现乳腺癌、结肠癌、直肠癌、卵巢癌的癌症死亡率与区域太阳 UV-B 辐射暴露（维生素 D 的主要来源）之间存在负相关；前列腺、胃、膀胱、食道、肾、肺、胰腺和子宫，以及非霍奇金淋巴瘤和多发性骨髓瘤。维生素 D 的抗癌作用得到了体外、动物和流行病学研究的有力支持。尽管现在有大量证据表明低维生素 D 摄入量和低血清 25-羟基维生素 D (25OHD) 与各种癌症风险增加有关，但尚未发现维生素 D 状态对所有癌症发病率影响的报告。此外，尚无随机临床试验报道使用维生素 D 干预足以将血清 25OHD 提高至最佳水平并针对癌症结果。我们小组最近进行的一项基于人群的研究旨在确定健康绝经后女性补充钙和维生素 D3 的抗骨折功效，结果表明维生素 D3 可以降低所有癌症的发病率。这些发现需要通过以癌症发病率作为主要结果变量设计的随机对照临床试验来证实。在此应用中，我们建议在 60 岁以上绝经后妇女的人群样本中测试将血清 25OHD 提高到最佳水平，同时保持足够的钙摄入量是否可以降低癌症的发病率。具体目标是： 1. 从内布拉斯加州 9 个邻近农村县随机抽取 60 岁及以上健康独立生活的绝经后妇女群体； 2. 招募 2300 名女性参加干预研究，将她们随机分配到 2 个治疗组中的 1 个：1）维生素 D3（2000 ID/天）和钙（1200 mg/天），或 2）维生素 D3 安慰剂和钙安慰剂，并对每个受试者进行 4 年跟踪； 3. 如果发现干预措施可有效降低癌症发病率，则收集并储存每位受试者的白细胞以检测遗传标记； 4.确定补充维生素D3对所有类型癌症综合发病率的影响； 5. 在巢式病例对照研究中确定随机和研究第 1 年结束时收集的血清 25OHD 与 4 年以上癌症风险之间的关联。每次半年访视时，将评估以下内容：病史和社会史；不良事件；癌症诊断；以及坚持服用补充剂/安慰剂。每年，我们将获取身高和体重并分析血清 25OHD 和 1,25-二羟基维生素 D。在基线和随访结束时，我们将评估饮食摄入量和体力活动。拟议的研究旨在实现 NCI 战略计划的目标，即“到 2015 年消除癌症造成的痛苦和死亡”。它具体涉及战略目标 2，即“加速癌症预防的进展”。我们提出的营养干预研究的积极结果将带来一种廉价、安全的预防癌症的方法。