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）：长期以来，维生素D（VIT D）在维持最佳骨骼健康中的关键作用已被认识到，但是它在调节先天免疫反应和炎症反应中的作用直到最近才进行了积极的研究。因此，VIT D是越来越多地选择和处方的高剂量饮食补充剂，因为它被认为可以改善各个年龄段的健康患者的免疫和炎症状态，以及包括HIV/AIDS在内的慢性疾病的人。 VIT D还具有对骨骼健康必不可少的钙化功能，VIT D状态差有助于与抗逆转录病毒疗法相关的骨质减少/骨质疏松症（ART）。 VIT 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，所有这些癌症可能会使HIV/AIDS及其治疗复杂化。 VIT D状态差在所有年龄段的艾滋病毒/艾滋病患者中很常见，例如年龄，皮肤色素，乳糖不耐症和日晒会改变VIT D缺乏症的风险。在美国的多中心涉及青少年（72％的非洲裔美国人）的研究中，有和没有HIV的研究表明，在最近来自Pharadelphia的健康非裔美国儿童中，有87％的血清25-羟基维生素D3（25D）浓度（25D）浓度（<15 ng/ml）。在美国，年轻的非裔美国人受HIV感染的影响不成比例（在13至24岁的艾滋病毒患者中约为55％），非裔美国人也有很高的VIT D缺乏症风险。 VIT D疗法有很大的希望可以改善我们的HIV/AIDS患者的主要医疗状况和生活质量，但是尚未对维生素D在治疗HIV/AIDS治疗中的潜在作用。迫切需要精心设计的随机试验以确定补充维护的安全性和功效。 研究人员提出了一项两阶段的研究，以建立艾滋病毒/艾滋病儿童和成人高剂量补充的安全性和功效。在研究第一阶段，在44名5.0至24.9岁的44名受试者中，确定了两种口服VIT D3剂量（4000和7000 IU/D）的安全性和功效。关键的安全措施同时升高血清钙和25D浓度。通过血清25D浓度和cathelicidin（先天免疫，抗菌蛋白）mRNA表达评估功效。研究阶段II是一个12个月，双盲，随机，安慰剂控制的补充研究（n = 52）。关键结果包括在目标范围内（32至160 ng/mL）内的安全性和长期25D浓度，改善了cate依蛋白mRNA的表达以及骨，肌肉，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。基于证据和诺言，VIT D显然应该成为国家免费医学中心（NCCAM）HIV研究计划中评估的首批营养素之一。 公共卫生相关性：最佳的维生素D浓度和代谢对于儿童，青少年和患有HIV/AIDS的成年人的正常免疫功能，生长，肌肉，骨骼和炎症状态至关重要。将使用临床上重要的结果评估补充维生素D的影响，以确保安全性和功效，这将克服在研究和临床护理中补充维生素D的关键障碍。廉价且易于管理，补充维生素D可能被证明是一种有效且可行的治疗方法，可用于症状和预防美国和世界各地艾滋病毒/艾滋病患者的副作用。