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: 8122356
• 负责人: VIRGINIA A. STALLINGS
• 金额: $ 55.28万
• 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 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8122356
• 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中的关键作用早已被认识到，但其在调节先天免疫应答和炎症反应中的作用最近才得到积极研究。因此，维生素D是一种越来越频繁选择和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健康人群以及慢性疾病（包括艾滋病毒/艾滋病）患者的免疫和炎症状态。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状态差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HIV/AIDS及其治疗复杂化。维生素D缺乏症在所有年龄段的艾滋病毒/艾滋病患者中很常见，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缺乏症的风险。在多中心美国REACH青少年研究（72%的非洲裔美国人）中，有和没有艾滋病毒，显示87%的血清25-羟基维生素D3（25 D）浓度低（<15 ng/mL），而最近来自费城的健康非洲裔美国儿童样本中的这一比例为34%。在美国，年轻的非洲裔美国人不成比例地受到艾滋病毒感染的影响（13至24岁的艾滋病毒感染者中约55%是非洲裔美国人），并且也处于维生素D缺乏症的高风险中。维生素D疗法在改善艾滋病毒/艾滋病患者的主要医疗条件和生活质量方面有很大的希望，但维生素D在治疗艾滋病毒/艾滋病方面的潜在作用尚未得到正式测试。迫切需要设计良好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的研究，以确定高剂量维生素D补充剂在儿童和成人中的安全性和有效性。在I期研究中，在44名年龄为5.0至24.9岁的受试者中确定了两种口服维生素D3剂量（4000和7000 IU/d）在12周内的安全性和疗效。关键的安全性指标是同时升高血清钙和25 D浓度。通过血清25 D浓度和抗菌肽（先天免疫，抗菌蛋白）mRNA表达评价疗效。II期研究是一项为期12个月、双盲、随机、安慰剂对照补充研究（n=52）。关键结果包括安全性和目标范围内的长期25 D浓度（32至160 ng/mL），改善的cathecidin mRNA表达，以及骨骼、肌肉、炎症、生长和身体组成状态以及HIV/AIDS疾病严重程度的测量。根据证据和承诺，维生素D显然应该成为国家免费和替代医学中心（NCCAM）艾滋病毒研究计划中评估的第一批营养素之一。 公共卫生相关性：最佳的维生素D浓度和代谢对于HIV/AIDS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补充剂价格便宜，易于管理，可能被证明是一种有效和可行的治疗症状和预防副作用的人的所有年龄的艾滋病毒/艾滋病在美国和世界各地。