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: 7580381
• 负责人: JOAN LAPPE
• 金额: $ 82.9万
• 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/7580381
• 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; Disease; Double-Blind Method; Enrollment; Epidemiologic Studies; Epidemiology; Esophagus; Foundations; Future; Genetic Markers; Genus Cola; 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; leukemia/lymphoma; malignant breast neoplasm; men; mortality; population based; prevent; primary outcome; public health relevance; 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 (vit D), has been found for cancers of the breast, colon, rectum, ovary, prostate, stomach, and numerous other cancers. Dietary and serum studies also demonstrate that vit D is a risk factor in colonic adenomas and for numerous cancers. The anticancer effect of vit D is strongly supported by in vitro and animal studies. However, no randomized clinical trials have used a vit D intervention sufficient to raise serum 25OHD to optimum levels and have targeted a cancer outcome. We reported a double-blind, placebo-controlled, randomized trial of calcium (Ca) and vit D supplementation in a population-based sample of postmenopausal women. A secondary objective of that study was to determine the efficacy of Ca alone and of Ca plus vit D3 in reducing risk of cancer of all types. We found that vit D3 significantly reduced the risk of all-types cancer by 60%. These findings need to be confirmed with a clinical trial designed with incidence of cancer as the primary outcome. In this application we propose to test whether increasing serum 25OHD to optimal levels, while maintaining adequate Ca 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 rural counties; 2. Enroll 2300 women into an intervention study, assign them randomly to 1 of 2 treatment groups: 1) vit D3 (2000 IU/d) and Ca (1200 mg/d), or 2) vit D3 placebo and Ca 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; 4. Determine the effect of supplementation with vit D3 on incidence of all types of cancer combined; 5. Determine in a nested-case control study the association of serum 25OHD collected at baseline and the end of year 1 with risk of cancer over 4 years; 6. Determine the effect of supplementation with calcium and vit D3 on incidence of specific cancers: breast, lung, colon and myeloma, leukemia, lymphoma. 7. Determine the effect of supplementation on incidence of other disorders, specifically hypertension, cardiovascular disease, osteoarthritis, colonic adenomas and diabetes, upper respiratory infections and falls. At each 6-mo visit, we will assess: medical and social history; adverse events; cancer diagnoses; and adherence to supplement/placebo. Annually, we will obtain height and weight and analyze serum 25OHD. At baseline and end of 4 yrs, 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 nutritional intervention study will result in an inexpensive, safe method of preventing cancer. PUBLIC HEALTH RELEVANCE: Project Narrative The purpose of this project is to determine whether, in a rigorous clinical trial, vitamin D3 and calcium supplementation decreases risk of all types of cancer. Positive findings will provide support for health policy changes to promote optimal vitamin D levels in the population.

描述（由申请人提供）： 癌症死亡率与区域太阳UV-B辐射暴露之间存在反比相关性，即维生素D（VIT D）的主要来源，是针对乳腺癌，结肠癌，直肠，卵巢，卵巢，前列腺，前列腺，胃和许多其他癌症的主要来源。饮食和血清研究还表明，VIT D是结肠腺瘤和许多癌症的危险因素。 VIT D的抗癌作用得到了体外和动物研究的强烈支持。但是，尚无随机临床试验使用足以将血清25OHD提高到最佳水平的VIT D干预措施，并针对癌症结果。我们报道了在绝经后妇女的基于人群的钙（CA）和VIT D补充的双盲，安慰剂对照，随机试验。该研究的次要目标是确定单独的CA和CA加VIT D3在降低所有类型癌症风险方面的功效。我们发现，VIT D3将全型癌症的风险显着降低了60％。这些发现需要通过以癌症为主要结果的临床试验来确认这些发现。在此应用中，我们建议测试将血清25OHD提高到最佳水平，同时保持足够的CA摄入量，从而降低了60岁以上的绝经后妇女样本中的癌症发生率。具体的目的是：1。随机样本从9个乡村县的60岁及60岁以上的健康独立后妇女的人口进行样本； 2。将2300名妇女纳入干预研究，将其随机分配给2个治疗组中的1个：1）VIT D3（2000 IU/D）和CA（1200 mg/d），或2）Vit D3安慰剂和CA安慰剂，并遵循每个受试者4年； 3.如果发现干预措施有效，则从每个受试者中收集和存储白细胞进行遗传标记的测试； 4。确定补充VIT D3对所有类型癌症的发生率的影响； 5。在一项嵌套对照研究中确定血清25OHD在基线和第1年底收集的血清25OHD与4年以内的癌症风险。 6。确定补充钙和VIT D3对特定癌症发生率的影响：乳腺癌，肺，结肠癌和骨髓瘤，白血病，淋巴瘤。 7。确定补充对其他疾病的发生的影响，特别是高血压，心血管疾病，骨关节炎，结肠腺瘤和糖尿病，上呼吸道感染和跌倒。在每次6点访问时，我们将评估：医学和社会历史；不利事件；癌症诊断；并遵守补充/安慰剂。每年，我们将获得身高和体重，并分析血清25OHD。在基线和4年结束时，我们将评估饮食摄入和体育锻炼。拟议的研究旨在解决NCI战略计划的目标，即“消除到2015年癌症引起的痛苦和死亡。”它专门针对战略目标2，以“加速预防癌症的进展”。我们的营养干预研究的积极发现将导致一种廉价，安全的预防癌症方法。公共卫生相关性：项目叙述该项目的目的是确定在严格的临床试验中，维生素D3和补充钙补充剂是否会降低所有类型的癌症的风险。积极的发现将为健康政策变化提供支持，以促进人群中最佳的维生素D水平。