Role of Vitamin D in the Prevention and Progression of Urinary Incontinence

维生素 D 在预防和治疗尿失禁中的作用

• 批准号: 9901526
• 负责人: Alayne Denise Markland
• 金额: $ 35.39万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9901526
• 关键词: Adipose tissue; Adult; Affect; African American; Aging; Ancillary Study; Attention; Biological Availability; Bladder; Blood specimen; Cholecalciferol; Clinical; Clinical Trials; Data; Dietary intake; Dose; Early treatment; Extravasation; Fracture; Frequencies; Future; Goals; Health; High Prevalence; Incidence; Inflammation; Intake; Intervention; Italy; Knowledge; Lead; Link; Longitudinal Studies; Low Prevalence; Measures; Mental Health; National Health and Nutrition Examination Survey; Nocturia; Nurses' Health Study; Nursing Homes; Obesity; Omega-3 Fatty Acids; Organ; Outcome; Overactive Bladder; Participant; Pathway interactions; Patients; Pelvic Floor Muscle; Personal Satisfaction; Pharmaceutical Preparations; Pharmacology; Pigmentation physiologic function; Placebos; Plasma; Prevalence; Prevention; Production; Prostate; Quality of life; Randomized; Research; Risk; Risk Factors; Role; Sampling; Series; Severities; Subgroup; Supplementation; Symptoms; Targeted Research; Text; Time; Urethra; Urge Incontinence; Urinary Incontinence; Urine; Vitamin D; Vitamin D Deficiency; Vitamin D supplementation; Vitamin D3 Receptor; Woman; Work; adult obesity; associated symptom; body system; clinically relevant; cohort; cost; delta opioid receptor; design; detrusor muscle; epidemiology study; falls; follow-up; functional decline; high risk; high risk population; improved; incontinence symptom; innovation; intervention cost; lower urinary tract symptoms; men; micturition urgency; novel; pilot trial; prevent; prospective; randomized trial; side effect; symptomatic improvement; targeted treatment; treatment strategy; trend

PROJECT SUMMARY Overactive bladder (OAB), the presence of urgency, frequency, and nocturia, is common with aging, as is urgency urinary incontinence (UUI). These are among the most bothersome lower urinary tract symptoms – associated with worse mental health, poor physical well-being, and increased falls, fractures, and nursing home placement. Despite treatment options, many patients do not become symptom-free and discontinue medications due to side effects or perceived inefficacy. Attention is shifting to possible prevention and early treatment strategies. Potential benefits of vitamin D may extend to several relevant organ systems, and vitamin D could act via multiple pathways to reduce lower urinary tract symptoms by improving detrusor activity and decreasing inflammation. Indeed, evidence emerging from epidemiologic studies indicate that higher vitamin D levels are associated with decreased risk for OAB and UI. In this revision application, we will leverage two large, complementary epidemiologic studies – the VITamin D and omegA-3 TriaL (VITAL, n=25,000 women and men) and the observational Nurses’ Health Studies (n>100,000 women) -- to conduct a rich exploration of vitamin D and OAB, as well as UUI. In this revision, we extend research to both OAB and UUI, increasing clinical relevance by broadening the outcomes (previously only UI) while focusing on symptoms related to detrusor contractility. We also improve innovation by targeting research in: (1) African Americans (n=2300 in NHS, n=5200 in VITAL), who disproportionately suffer from OAB and UUI, and have higher prevalence of vitamin D deficiency; and in (2) obese adults (n=34,000 in NHS, n=7200 in VITAL), who are at higher risk of OAB and UUI, and have lower bioavailability of vitamin D as it is retained in adipose tissue. Our main Aims are to: 1) assess if vitamin D3 supplementation decreases OAB and UUI in VITAL, where participants have been assigned to 2000IU/day of vitamin D or placebo for five years, and in NHS, where observational data are available on a large range of doses, from <400 IU to >800 and >1000 IU/day; and 2) to prospectively assess if higher plasma 25(OH)D levels at baseline are related to a decreased incidence and progression of UUI in the NHS. In VITAL, where an estimated 50% of participants had 25(OH)D<30ng/mL at baseline, we propose to collect data on OAB and UI symptoms at year 5 by adding new questions on urgency, frequency, nocturia and urine leakage at the close of the trial. The NHS already includes extensive UUI data, and we will newly measure baseline vitamin D levels from stored blood samples and add OAB questions in upcoming follow-up periods. The large samples of African American and of obese adults in these cohorts uniquely enable important and novel research. The expected outcomes will be to provide exciting new knowledge regarding vitamin D as a possible convenient, low-cost intervention for preventing OAB and UUI symptoms and progression among women and men, specifically targeting high-risk subgroups of African Americans and obese adults.

项目概要 膀胱过度活动症（OAB），即尿急、尿频和夜尿的症状，在衰老过程中很常见， 急迫性尿失禁（UUI）。这些是最令人烦恼的下尿路症状 - 与心理健康状况较差、身体健康状况不佳以及跌倒、骨折和护理次数增加有关 居家安置。尽管有多种治疗选择，但许多患者并没有消除症状并停止治疗 由于副作用或认为无效而服用的药物。注意力正在转向可能的预防和早期预防 治疗策略。维生素 D 的潜在益处可能会延伸到多个相关器官系统，并且维生素 D D 可以通过多种途径发挥作用，通过改善逼尿肌活动和减少下尿路症状 减少炎症。事实上，流行病学研究的证据表明，较高的维生素 D 水平与 OAB 和 UI 风险降低相关。 在此修订申请中，我们将利用两项大型、互补的流行病学研究 – 维生素 D 和 omegA-3 TriaL（VITAL，n=25,000 名女性和男性）以及观察性护士健康研究 （n>100,000 名女性）——对维生素 D 和 OAB 以及 UUI 进行丰富的探索。在本次修订中，我们 将研究扩展到 OAB 和 UUI，通过扩大结果来提高临床相关性（之前 仅 UI），同时关注与逼尿肌收缩力相关的症状。我们还通过瞄准来提高创新 研究对象：(1) 非裔美国人（NHS 中 n=2300，VITAL 中 n=5200），他们不成比例地患有 OAB 和 UUI，维生素 D 缺乏症的患病率较高； (2) 肥胖成年人（NHS 中 n=34,000， VITAL 中 n=7200），这些人患有 OAB 和 UUI 的风险较高，并且维生素 D 的生物利用度较低 保留在脂肪组织中。我们的主要目标是：1) 评估补充维生素 D3 是否可以降低 OAB 和 VITAL 中的 UUI，参与者被分配每天 2000IU 的维生素 D 或安慰剂，为期五年，以及 在 NHS 中，可以获得大范围剂量的观察数据，从 <400 IU 到 >800 和 >1000 国际单位/天； 2) 前瞻性评估基线时血浆 25(OH)D 水平较高是否与血浆 25(OH)D 水平降低有关 NHS 中 UUI 的发生率和进展。在 VITAL 中，估计有 50% 的参与者 基线时 25(OH)D<30ng/mL，我们建议在第 5 年通过添加新的内容来收集 OAB 和 UI 症状的数据 试验结束时询问尿急、尿频、夜尿和漏尿情况。 NHS 已经包括 广泛的 UUI 数据，我们将重新测量储存的血液样本中维生素 D 的基线水平，并添加 OAB 在接下来的后续阶段提出问题。非洲裔美国人和肥胖成年人的大量样本 这些群体独特地促进了重要且新颖的研究。预期成果将是提供 关于维生素 D 的令人兴奋的新知识可能是一种方便、低成本的干预措施 预防女性和男性的 OAB 和 UUI 症状及其进展，特别针对 非裔美国人和肥胖成年人的高风险亚群。