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.

项目摘要 膀胱过度活动症（OAB），即尿急、尿频和尿急的存在，与衰老有关， 急迫性尿失禁（UUI）。这些是最麻烦的下尿路症状之一- 与心理健康状况恶化、身体健康状况差以及福尔斯、骨折和护理增加相关 家庭安置。尽管有治疗选择，但许多患者并没有完全摆脱疾病，而是停药 药物由于副作用或感知无效。注意力正在转向可能的预防和早期 治疗策略。维生素D的潜在益处可能扩展到几个相关的器官系统， D可以通过多种途径发挥作用，通过改善逼尿肌活动来减轻下尿路症状， 减少炎症。事实上，流行病学研究的证据表明， 水平与OAB和UI风险降低相关。 在本修订申请中，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。在这次修订中，我们 将研究扩展到OAB和UUI，通过扩大结局（以前）增加临床相关性 仅UI），同时关注与逼尿肌收缩性相关的症状。我们还通过针对 研究对象：（1）非裔美国人（NHS中n=2300，VITAL中n=5200），不成比例地患有OAB 和UUI，并且具有较高的维生素D缺乏症患病率;以及在（2）肥胖成年人（NHS中n= 34，000， n=7200（在VITAL中），他们患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。我们的主要目的是：1）评估维生素D3补充是否会降低OAB， VITAL中的UUI，参与者被分配接受2000 IU/天的维生素D或安慰剂治疗五年， 在NHS中，可获得大范围剂量的观测数据，从<400 IU to >800到&gt;1000 IU/天;和2）前瞻性评估基线时较高的血浆25（OH）D水平是否与 NHS中UUI的发病率和进展。在VITAL中，估计有50%的参与者 基线时25（OH）D&lt;30 ng/mL，我们建议通过添加新的 试验结束时询问有关尿急、尿频、夜尿和漏尿的问题。NHS已经包括 广泛的UUI数据，我们将从储存的血液样本中重新测量基线维生素D水平，并添加 在接下来的随访期间，OAB问题。美国黑人和肥胖成年人的大样本 这些群体独特地使重要和新颖的研究成为可能。预期的结果将是提供 令人兴奋的新知识，关于维生素D作为一种可能的方便，低成本的干预， 预防女性和男性的OAB和UUI症状和进展，特别针对 非裔美国人和肥胖成年人的高风险亚组。