Safe and Effective Vitamin D Supplementation in HIV

治疗艾滋病毒时安全有效的维生素 D 补充剂

• 批准号: 8325453
• 负责人: VIRGINIA A. STALLINGS
• 金额: $ 55.03万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8325453
• 关键词: AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Adolescent; Adult; Adverse effects; Adverse event; Affect; African American; Age; Age Factors; Alkaline Phosphatase; Alternative Medicine; Biological Markers; Blood Pressure; Body Composition; Calcifediol; Calcium; Centers for Disease Control and Prevention (U.S.); Child; Childhood; Cholecalciferol; Chronic Disease; Classification; Clinical Trials; Complex; Cyclophosphamide; Data; Dietary Intervention; Disease Progression; Dose; Double-Blind Method; Equilibrium; Evaluation; Fat-Soluble Vitamin; Gender; Glucose; Goals; Growth; HIV; HIV Infections; Hand; Health; Height; Host Defense; Immune; Immune response; Incidence; Infection; Inflammation; Inflammatory; Insulin; Intake; Intervention Studies; Investigation; Lactose Intolerance; Life; Malignant Neoplasms; Measures; Medical; Metabolism; Muscle; Muscle function; Mycobacterium tuberculosis; Natural Immunity; Neopterin; Nutrient; Oral; Osteopenia; Osteoporosis; Outcome; Participant; Pathway interactions; Patients; Persons; Phase; Philadelphia; Pigments; Pilot Projects; Placebo Control; Placebos; Play; Prevention; Proteins; Quality Indicator; Quality of life; Race; Randomized; Reaction; Recommendation; Research; Research Personnel; Resources; Risk; Role; Safety; Sampling; Serum; Severity of illness; Skin Aging; Source; Sun Exposure; Supplementation; Symptoms; Testing; Vitamin D; Vitamin D Deficiency; Weight; Youth; aged; animal data; antimicrobial; antiretroviral therapy; base; bone; bone health; bone mass; bone strength; cathelicidin; clinical care; design; dietary supplements; experience; grasp; high risk; immune function; improved; lipid metabolism; mRNA Expression; muscle strength; nutrition; patient population; phase 1 study; phase 2 study; prepuberty; programs; public health relevance; quadriceps muscle; randomized trial; treatment trial

DESCRIPTION (provided by applicant): The key role of vitamin D (vit D) in maintaining optimal bone health has long been recognized, but its role in modulating the innate immune response and inflammatory reaction has only recently come under active investigation. As such, vit D is an increasingly frequently chosen and prescribed high dose dietary supplement, because it is thought to improve immune and inflammatory status in healthy people of all ages, and in those with chronic diseases including HIV/AIDS. Vit D also has calciotrophic functions essential for bone health, and poor vit D status contributes to the osteopenia/osteoporosis associated with antiretroviral therapy (ART). Vit D may improve insulin/glucose/lipid metabolism, blood pressure, and risk of some cancers, all of which may complicate HIV/AIDS and its treatments. Poor vit D status is common in HIV/AIDS patients of all ages and factors such as age, skin pigment, lactose intolerance, and sun exposure alter the risks for vit D deficiency. In the multicenter U.S. REACH study of adolescents (72% African American), with and without HIV, showed that 87% had low serum 25-hydroxyvitamin D3 (25D) concentrations (<15 ng/mL), compared to 34% in a recent sample of healthy African American children from Philadelphia. Young African Americans are disproportionately affected by HIV infection in the US (~ 55% among persons with HIV aged 13 to 24 years are African American), and are also at high risk for vit D deficiency. Vit D therapy has great promise to improve major medical conditions and the quality of life for our HIV/AIDS patients, yet the potential role of vitamin D in the treatment of HIV/AIDS has not been formally tested. Well-designed randomized trials are urgently needed to determine vit D supplementation safety and efficacy. The investigators propose a two-phase study to establish safety and efficacy of high dose vit D supplementation in children and adults with HIV/AIDS. In Study Phase I, the safety and efficacy of two oral vit D3 doses (4000 and 7000 IU/d) are determined over 12 weeks in 44 subjects ages 5.0 to 24.9 years. The key safety measure is concurrently elevated serum calcium and 25D concentrations. Efficacy is evaluated by serum 25D concentration and cathelicidin (innate immune, antimicrobial protein) mRNA expression. Study Phase II is a 12 month, double blind, randomized, placebo controlled supplementation study (n=52). Key outcomes include safety and long- term 25D concentration within the goal range (32 to 160 ng/mL), improved cathecidin mRNA expression, and measures of bone, muscle, inflammation, growth and body composition status, and HIV/AIDS disease severity. Based on the evidence and promise, vit D clearly deserves to be among the first nutrients evaluated in the National Center for Complimentary and Alternative Medicine (NCCAM) HIV research program. PUBLIC HEALTH RELEVANCE: Optimal vitamin D concentration and metabolism are essential for normal immune function, growth, muscle, bone, and inflammatory status in children, adolescents and adults with HIV/AIDS. The impact of vitamin D supplementation will be evaluated for safety and efficacy using clinically important outcomes, and this will overcome the critical barrier for use of vitamin D supplementation in research and clinical care. Inexpensive and easy to administer, vitamin D supplementation may prove to be an effective and feasible treatment for symptoms and prevention of side effects for people of all ages living with HIV/AIDS in the US and around the world.

描述（由申请人提供）：维生素 D (vit D) 在维持最佳骨骼健康方面的关键作用早已被认识到，但其在调节先天免疫反应和炎症反应中的作用直到最近才得到积极研究。因此，维生素 D 成为越来越多地被选择和开处方的高剂量膳食补充剂，因为它被认为可以改善所有年龄段的健康人群以及患有艾滋病毒/艾滋病等慢性疾病的人的免疫和炎症状态。维生素 D 还具有对骨骼健康至关重要的钙营养功能，维生素 D 状态不佳会导致与抗逆转录病毒治疗 (ART) 相关的骨质减少/骨质疏松症。维生素 D 可以改善胰岛素/葡萄糖/脂质代谢、血压和某些癌症的风险，所有这些都可能使艾滋病毒/艾滋病及其治疗复杂化。维生素 D 状况不佳在所有年龄段的 HIV/艾滋病患者中都很常见，年龄、皮肤色素、乳糖不耐受和阳光照射等因素会改变维生素 D 缺乏的风险。在针对感染或未感染 HIV 的青少年（72% 非洲裔美国人）进行的多中心美国 REACH 研究中，87% 的青少年血清 25-羟基维生素 D3 (25D) 浓度较低（<15 ng/mL），而最近的一项研究中这一比例为 34%。来自费城的健康非洲裔美国儿童样本。在美国，年轻的非裔美国人受 HIV 感染的影响尤为严重（13 至 24 岁的 HIV 感染者中约 55% 是非裔美国人），而且维生素 D 缺乏的风险也很高。维生素 D 疗法有望改善 HIV/AIDS 患者的主要医疗状况和生活质量，但维生素 D 在 HIV/AIDS 治疗中的潜在作用尚未得到正式测试。迫切需要精心设计的随机试验来确定维生素 D 补充剂的安全性和有效性。 研究人员提出了一项两阶段研究，以确定高剂量维生素 D 补充剂对感染艾滋病毒/艾滋病的儿童和成人的安全性和有效性。在研究 I 期中，在 44 名年龄为 5.0 至 24.9 岁的受试者中，在 12 周内确定了两种口服 vit D3 剂量（4000 和 7000 IU/天）的安全性和有效性。关键的安全措施是同时升高血清钙和 25D 浓度。通过血清 25D 浓度和导管素（先天免疫、抗菌蛋白）mRNA 表达来评估疗效。研究 II 期是一项为期 12 个月的双盲、随机、安慰剂对照补充研究 (n=52)。主要成果包括安全性和长期 25D 浓度在目标范围内（32 至 160 ng/mL）、改善的组织肽 mRNA 表达以及骨骼、肌肉、炎症、生长和身体成分状态以及 HIV/AIDS 疾病严重程度的测量。基于证据和承诺，维生素 D 显然值得成为国家补充和替代医学中心 (NCCAM) HIV 研究计划评估的首批营养素之一。 公众健康相关性：最佳维生素 D 浓度和代谢对于艾滋病毒/艾滋病儿童、青少年和成人的正常免疫功能、生长、肌肉、骨骼和炎症状态至关重要。将使用临床重要结果评估维生素 D 补充剂的安全性和有效性，这将克服在研究和临床护理中使用维生素 D 补充剂的关键障碍。维生素 D 补充剂价格低廉且易于管理，对于美国和世界各地所有年龄段的艾滋病毒/艾滋病感染者来说，维生素 D 补充剂可能被证明是一种有效且可行的症状治疗方法和预防副作用的方法。