Vitamin D Supplementation in Veterans with Early-Stage Prostate Cancer

患有早期前列腺癌的退伍军人补充维生素 D

• 批准号: 8195961
• 负责人: SEBASTIANO GATTONI-CELLI
• 金额: --
• 依托单位: RALPH H JOHNSON VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-10-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8195961
• 关键词: Biopsy; Biopsy Specimen; Caring; Cell Death; Chemopreventive Agent; Cholecalciferol; Clinical; Clinical Research; Diagnosis; Disease; Dose; Enrollment; Epithelial Cells; Evaluation; Gleason Grade for Prostate Cancer; Histologic; Malignant neoplasm of prostate; Measurable; Measurement; Measures; Medical; Monitor; Needle biopsy procedure; PSA level; Pathology; Phenotype; Placebo Control; Prostate; Randomized; Regimen; Risk; Serum; Staging; Supplementation; Testing; Time; Tissues; Veterans; Vitamin D; Vitamin D Deficiency; Vitamin Deficiency; base; cancer cell; improved; men; outcome forecast; prevent; public health relevance; serum PSA

Vitamin D promotes the differentiation of prostate cancer (PCa) cells, maintains the differentiated phenotype of prostate epithelial cells, and can induce prostate cancer cell death, raising the possibility that vitamin D deficiency over time promotes the progression of subclinical PCa to clinical disease. This is particularly relevant to men WHO ARE DEFICIENT IN CIRCULATING (SERUM) VITAMIN D [<20 NG/ML 25(OH)D3]. These considerations support the use of vitamin D3 as a chemopreventive agent, especially in SUBJECTS WITH HYPOVITAMINOSIS D. We hypothesize that a daily dose of vitamin D3 (4,000 IU) taken for one year by Veterans diagnosed with low- risk, early-stage PCa, who are eligible for active surveillance AND ARE DEFICIENT IN CIRCULATING (SERUM) VITAMIN D [<20 NG/ML 25(OH)D3]will: a) result in a measurable decrease of serum PSA levels in a significant number of enrolled subjects, and b) be associated with a stabilization or improvement of their PCa pathology, as assessed through histologic examination of prostate tissue biopsy specimens (Gleason score and percent of positive biopsies) obtained at the end of the study, as part of their standard medical care for active surveillance. This VA Merit application proposes to conduct a randomized, placebo-controlled clinical study aimed at measuring the efficacy of vitamin D3 (4000IU/day) supplementation in Veterans diagnosed with early-stage prostate cancer, who elect to have their disease monitored through active surveillance (before considering definitive therapy) AND ARE DEFICIENT IN CIRCULATING (SERUM) VITAMIN D [<20 NG/ML 25(OH)D3]. The main objectives of this proposed clinical study are as follows: 1) To determine whether a daily supplement of 4,000 IU of vitamin D3 taken for twelve months will result in a measurable and significant decrease of serum PSA levels in Veterans diagnosed with low-risk, early stage PCa (Gleason score d6, PSA d10, clinical stage T1C or T2a), who elect to have their disease monitored through active surveillance for at least one year AND ARE DEFICIENT IN CIRCULATING (SERUM) VITAMIN D [<20 NG/ML 25(OH)D3]. 2) To determine in enrolled Veterans the pathology status of their PCa by analyzing prostate tissue biopsy specimens at the end of the study (Gleason score and percentage of positive biopsies), and by comparing them with those obtained before enrollment in this study, as part of their standard medical care. The implementation of these proposed studies will allow us to assess whether vitamin D3 supplementation can be utilized as a chemopreventive regimen in Veterans diagnosed with low- risk, early stage PCa, and provide a useful addition to active surveillance.

维生素 D 促进前列腺癌 (PCa) 细胞的分化，维持其分化表型 前列腺上皮细胞，并且可以诱导前列腺癌细胞死亡，这增加了维生素 D 的可能性 随着时间的推移，缺乏会促进亚临床 PCa 进展为临床疾病。这一点特别 与循环（血清）维生素 D 缺乏 [<20 NG/ML 25(OH)D3] 的男性相关。这些 考虑因素支持使用维生素 D3 作为化学预防剂，特别是在患有以下疾病的受试者中： 维生素缺乏症 D. 我们假设被诊断患有低血压的退伍军人每天服用维生素 D3 剂量（4,000 IU）一年。 有风险、早期 PCa、有资格接受主动监测且循环（血清）不足的人 维生素 D [<20 NG/ML 25(OH)D3] 将： a) 导致血清 PSA 水平明显降低 入组受试者的数量，以及 b) 与其 PCa 病理学的稳定或改善相关， 通过前列腺组织活检标本的组织学检查进行评估（格里森评分和百分比 阳性活检）在研究结束时获得，作为其标准医疗护理的一部分 监视。 该 VA Merit 申请建议进行一项随机、安慰剂对照的临床研究，旨在 测量被诊断为早期阶段的退伍军人补充维生素 D3（4000IU/天）的功效 前列腺癌，选择通过主动监测来监测其疾病（在考虑之前 根治性治疗）并且缺乏循环（血清）维生素 D [<20 NG/ML 25(OH)D3]。主要 这项拟议的临床研究的目标如下： 1) 确定每日补充 4,000 IU 维生素 D3 连续 12 个月是否会导致 诊断为低风险早期阶段的退伍军人血清 PSA 水平可测量且显着降低 PCa（格里森评分 d6、PSA d10、临床分期 T1C 或 T2a），选择接受疾病监测 通过至少一年的主动监测并且缺乏循环（血清）维生素 D [<20 NG/ML 25(OH)D3]。 2) 通过分析前列腺组织活检来确定已登记退伍军人的 PCa 病理状态 研究结束时的标本（格里森评分和阳性活检百分比），并通过比较 将他们与参加本研究之前获得的数据进行比较，作为他们标准医疗护理的一部分。 这些拟议研究的实施将使我们能够评估维生素 D3 是否 补充剂可用作诊断患有低血压的退伍军人的化学预防方案 风险、早期 PCa，并为主动监测提供有用的补充。