Trial of Vitamin D Supplementation to Prevent TB Infection in Schoolchildren

补充维生素 D 预防学童结核感染的试验

基本信息

批准号：
9127321
负责人：
Ganmaa Davaasambuu
金额：
$ 65.5万
依托单位：
HARVARD SCHOOL OF PUBLIC HEALTH
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-18 至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9127321
关键词：
25-hydroxyvitamin D Adolescent Adult Adverse effects Age Antibiotics Biological Assay Bolus Infusion Cause of Death Cessation of life Child Childhood Cholecalciferol Clinical Trials Communicable Diseases Consensus Controlled Clinical Trials Development Disease Dose Double-Blind Method Emergency Situation HIV Health Immune response Immunity In Vitro Incidence Infection Interferon Type II Intervention Investments Lead Measures Meta-Analysis Mongolia Morbidity - disease rate Multidrug-Resistant Tuberculosis Mycobacterium tuberculosis Natural Immunity Oral Participant Pharmaceutical Preparations Phase Phase II Clinical Trials Placebo Control Placebos Policies Population Populations at Risk Predisposition Public Health Randomized Randomized Clinical Trials Regimen Risk Role Serum Supplementation Testing Time Tuberculosis Tuberculosis Vaccines United States Vaccination Vaccines Vitamin D Vitamin D Deficiency Vitamin D supplementation World Health Organization acquired immunity active method aged capsule cost dietary supplements editorial follow-up immune resistance improved mathematical model meetings mortality novel vaccines prevent primary outcome protective effect public health relevance scale up transmission process tuberculosis immunity vaccine candidate

项目摘要

DESCRIPTION (provided by applicant): Tuberculosis (TB) is an infectious disease that is a major global cause of morbidity and mortality: the World Health Organization (WHO) estimates that 8.7 million cases resulted in 1.4 million deaths worldwide in 2011. Most active TB cases arise in adults as a consequence of reactivation of a latent TB infection (LTBI) acquired in childhood. An estimated 2.3 billion people have LTBI, including 10-15 million people in the US. WHO aims to eliminate TB as a public health problem by 2050, and this will require measures to prevent acquisition of LTBI. Vitamin D has long been known to enhance innate immunity to Mycobacterium tuberculosis (MTB), and Phase 2 clinical trials show that vitamin D supplementation enhances innate immune resistance to MTB infection. We propose to conduct a Phase 3 double-blind randomized placebo-controlled clinical trial to determine whether vitamin D supplementation reduces risk of acquisition of LTBI in 7,350 uninfected schoolchildren aged 6-15 years in Ulaanbaatar, Mongolia, where rates of LTBI acquisition in children are particularly high as is vitamin D deficiency. Study medication will be administered over 3 years as 72 directly observed bi-weekly oral doses of 28,000 IU Vitamin D3 or placebo. We will employ a well-validated interferon-gamma release assay to determine whether participants have acquired LTBI at 3 years of follow-up (primary outcome). There is professional consensus, as highlighted in recent editorials in the Lancet [2011; 377:189-90] and PNAS [2011; 108, 18861-18862], that the trial we propose needs to be conducted. The PNAS editorial concludes that "It is a tragic irony that vitamin D, which costs a penny a day and may enhance innate and acquired immunity to TB, is not considered a worthy investment for critical clinical trials that could determine whether supplementation can prevent disease." The results of this trial will inform global TB control policy by determining whether vitamin D supplementation prevents acquisition of LTBI. More than one billion people worldwide are Vitamin D deficient, and supplementation is safe and inexpensive: intermittent bolus doses of vitamin D are effective in correcting deficiency, are inexpensive, easy to administer, have a very low incidence of adverse effects and much higher degree of acceptability than vaccines and antibiotics. The results of our trial will be readily generalizable to the vitamin D deficient populations at risk of TB worldwide and to the billions already infected with LTBI.

描述（由申请人提供）：结核病 (TB) 是一种传染病，是全球发病和死亡的主要原因：世界卫生组织 (WHO) 估计 2011 年全球有 870 万病例导致 140 万人死亡。最活跃的结核病成人病例的出现是由于儿童期获得的潜伏性结核感染 (LTBI) 重新激活所致。据估计，有 23 亿人患有 LTBI，其中美国有 10-1500 万人。世卫组织的目标是到 2050 年消除结核病这一公共卫生问题，这需要采取措施防止感染 LTBI。人们早就知道维生素 D 可以增强对结核分枝杆菌 (MTB) 的先天免疫，2 期临床试验表明补充维生素 D 可以增强对 MTB 感染的先天免疫抵抗力。我们建议开展一项 3 期双盲随机安慰剂对照临床试验，以确定补充维生素 D 是否可以降低蒙古乌兰巴托 7,350 名 6-15 岁未感染学童获得 LTBI 的风险，该国儿童 LTBI 获得率是尤其是维生素 D 缺乏症。研究药物将在 3 年的时间里进行，72 名直接观察者每两周口服 28,000 IU 维生素 D3 或安慰剂。我们将采用经过充分验证的干扰素-γ释放测定来确定参与者是否在 3 年随访时感染了 LTBI（主要结果）。正如《柳叶刀》最近的社论所强调的那样，存在专业共识[2011； 377:189-90] 和 PNAS [2011； 108, 18861-18862]，我们建议的试验需要进行。《美国国家科学院院刊》的社论总结道：“维生素 D 每天花费一便士，可能会增强对结核病的先天和后天免疫力，但它并不被认为是一项值得投资的关键临床试验，这些临床试验可以确定补充是否可以预防疾病，这是一个悲剧性的讽刺。 ”该试验的结果将确定补充维生素 D 是否可以预防 LTBI 的感染，从而为全球结核病控制政策提供参考。全球有超过 10 亿人缺乏维生素 D，补充维生素 D 既安全又便宜：间歇性推注剂量的维生素 D 可有效纠正缺乏症，价格便宜，易于管理，不良反应发生率极低，且改善程度更高。比疫苗和抗生素更容易接受。我们的试验结果很容易推广到全世界有结核病风险的缺乏维生素 D 的人群以及已经感染 LTBI 的数十亿人。