Safe and Effective Vitamin D Supplementation in HIV

描述(申请人提供)：维生素D(维生素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反应和炎症反应中的作用直到最近才受到积极研究。因此，维生素D是一种越来越频繁地被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的健康人以及包括艾滋病毒/艾滋病在内的慢性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状态不佳会导致抗逆转录病毒治疗(ART)相关的骨量减少/骨质疏松。维生素D可以改善胰岛素/糖/脂代谢、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艾滋病毒/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。在美国REACH多中心对青少年(72%的非裔美国人)、感染和未感染艾滋病毒的研究中，显示87%的人血清25-羟基维生素D3(25D)浓度较低(15 ng/毫升)，相比之下，最近费城健康的非裔美国儿童样本中的这一比例为34%。在美国，年轻的非裔美国人不成比例地受到艾滋病毒感染的影响(在13至24岁的艾滋病毒感染者中，约55%是非裔美国人)，并且也是维生素D缺乏症的高危人群。维生素D疗法很有希望改善我们艾滋病毒/艾滋病患者的主要医疗条件和生活质量，但维生素D在艾滋病毒/艾滋病治疗中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。研究人员建议进行两个阶段的研究，以确定大剂量维生素D补充在患有艾滋病毒/艾滋病的儿童和成人中的安全性和有效性。在研究第一阶段，对44名年龄在5.0到24.9岁的受试者进行了为期12周的两次口服维生素D3剂量(4000和7000IU/d)的安全性和有效性的测定。关键的安全措施是同时提高血钙和25D浓度。通过血清25D浓度和放线菌素(先天免疫，抗菌蛋白)mRNA的表达来评估疗效。第二阶段研究是一个为期12个月的双盲、随机、安慰剂对照补充研究(n=52)。主要结果包括安全和长期的25D浓度在目标范围内(32至160 ng/毫升)，改善了阳春素mRNA的表达，以及对骨骼、肌肉、炎症、生长和身体成分状况以及艾滋病毒/艾滋病严重程度的测量。根据证据和承诺，维生素D显然值得成为国家免费和替代医学中心(NCCAM)艾滋病毒研究计划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浓度和代谢对儿童、青少年和成人艾滋病毒/艾滋病患者的正常免疫功能、生长、肌肉、骨骼和炎症状态至关重要。维生素D补充剂的影响将根据临床上重要的结果进行安全性和有效性评估，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，易于管理，可能会被证明是一种有效和可行的治疗方法，可以治疗美国和世界各地所有年龄段的艾滋病毒/艾滋病患者的症状和预防副作用。

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.