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: 7788041
• 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 2012-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7788041
• 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

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: PROJECT NARRATIVE Vitamin D promotes the differentiation of prostate cancer 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 prostate cancer to clinical disease. We propose to conduct a clinical study aimed at measuring the efficacy of vitamin D3 (4000IU/day) supplementation in Veterans diagnosed with low-risk, early-stage prostate cancer, who elect to have their disease monitored through active surveillance. The successful completion of this proposed clinical study will allow us to determine whether correcting vitamin D deficiency [<20 ng/mL 25(OH)D3 at time of enrollment] in Veterans diagnosed with early- stage prostate cancer will prevent progression of their disease and improve their prognosis.

描述（由申请人提供）： 维生素D促进前列腺癌（PCa）细胞的分化，维持前列腺上皮细胞的分化表型，并且可以诱导前列腺癌细胞死亡，提高了维生素D缺乏随时间推移促进亚临床PCa进展为临床疾病的可能性。这与循环（血清）维生素D缺乏[<20 NG/ML 25（OH）D3]的男性特别相关。这些考虑支持将维生素D3用作化学预防剂，尤其是在维生素D缺乏症受试者中。我们假设每天摄入一定量的维生素D3（4，000 IU）由诊断为低风险，早期PCa的退伍军人服用一年，他们有资格进行主动监测并且缺乏循环（血清）维生素D [<20 NG/ML 25（OH）D3]将：a）导致大量入组受试者血清PSA水平的可测量降低，和B）与其PCa病理学的稳定或改善相关，通过在研究结束时获得的前列腺组织活检标本的组织学检查（Gleason评分和阳性活检的百分比）进行评估，作为他们主动监测的标准医疗护理的一部分。本VA Merit申请拟进行一项随机、安慰剂对照临床研究，旨在测量维生素D3（4000 IU/天）补充剂在诊断为早期前列腺癌的退伍军人中的疗效，这些退伍军人选择通过主动监测（在考虑确定性治疗之前）对其疾病进行监测，并且缺乏循环（血清）维生素D [<20 NG/ML 25（OH）D3]。本拟定临床研究的主要目的如下：1）确定每日补充4，000 IU维生素D3持续12个月是否会导致诊断为低风险早期PCa的退伍军人的血清PSA水平显著降低。（Gleason评分d 6，PSA d10，临床分期T1 C或T2 a），选择通过主动监测至少一年来监测其疾病并且缺乏循环（血清）维生素D [<20 NG/ML 25，OH）D3]。2)通过分析研究结束时的前列腺组织活检标本（Gleason评分和阳性活检百分比），并将其与入组本研究前获得的标本进行比较，确定入组退伍军人的PCa病理状态，作为其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补充剂是否可以用作诊断为低风险早期PCa的退伍军人的化学预防方案，并为主动监测提供有用的补充。 公共卫生相关性： 维生素D可促进前列腺癌细胞的分化，维持前列腺上皮细胞的分化表型，并可诱导前列腺癌细胞死亡，增加了维生素D缺乏随时间推移促进亚临床前列腺癌进展为临床疾病的可能性。我们建议进行一项临床研究，旨在测量维生素D3（4000 IU/天）补充剂在诊断为低风险早期前列腺癌的退伍军人中的疗效，这些退伍军人选择通过主动监测来监测他们的疾病。这项拟议的临床研究的成功完成将使我们能够确定在被诊断患有早期前列腺癌的退伍军人中纠正维生素D缺乏[在招募时<20 ng/mL 25（OH）D3]是否会防止他们的疾病进展并改善他们的预后。