Study of Acid Reflux Therapy for Children with Asthma

儿童哮喘胃酸反流治疗研究

• 批准号: 7474764
• 负责人: WILLIAM GERALD TEAGUE
• 金额: $ 38.37万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-20 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7474764
• 关键词: Acids; Adrenal Cortex Hormones; Age; Age-Years; Agonist; Asthma; Breathing; Bronchial Spasm; CYP2C19 gene; Child; Clinical; Clinical Trials; Clinical Trials Cooperative Group; Cytochrome P450; Dose; Effectiveness; Esophageal; Frequencies; Gastric Acid; Gastroesophageal reflux disease; Genetic Polymorphism; Goals; Healthcare; Hour; Improve Access; Individual; Inflammatory; Interleukin-1 beta; Interview; Lansoprazole; Masks; Measures; Medical; Metabolism; Monitor; Multi-Institutional Clinical Trial; Nitric Oxide; Nucleotides; Outcome Measure; Participant; Pathway interactions; Patients; Pharmaceutical Preparations; Placebos; Plasma; Production; Proton Pump Inhibitors; Randomized; Randomized Clinical Trials; Reflux; Research Personnel; Respiratory physiology; Safety; Score; Severities; Site; Subgroup; Symptoms; Teenagers; Testing; airway inflammation; cytokine; diaries; health related quality of life; improved; methacholine; programs; prospective; response

DESCRIPTION (provided by applicant): Gastroesophageal reflux (GER) is frequent in children with asthma, can induce bronchospasm, and increase airways reactivity. Children with asthma are often treated for GER with drugs to suppress gastric acid production. However, this treatment is expensive, and with unproven benefit. The primary objective in this proposal is to conduct a multi-site, randomized, clinical trial to test the hypothesis that treatment of GER with lansoprazole, an approved proton pump inhibitor, will decrease the frequency of exacerbations in children with poorly controlled asthma. The study will include 300 asthmatic children treated with inhaled corticosteroids, 6-16 years of age, with poor control defined by frequent symptoms, excessive beta agonist use, or frequent exacerbations. Participants will be randomly assigned to treatment with either lansoprazole or placebo for six months. The presence, severity, and relationship of GER to asthma symptoms will be determined with 24 hour esophageal pH monitoring, but randomization to treatment will not be influenced by the presences or severity of GER. The primary outcome measure is the proportion of participants who have exacerbations of asthma defined by diaries and interviews. Secondary outcome measures include asthma symptom and control scores, GER symptoms, lung function, and unscheduled health care contacts. Pre-defined subgroup analyses will examine the relationship between specific clinical features and the response to lansoprazole. Treatment response will also be evaluated with 3-hour post-dose plasma lansoprazole concentrations, and related to polymorphisms in CYP2C19, the cytochrome P450 pathway, and IL-1 beta, a pro-inflammatory cytokine. Tertiary studies will determine how the magnitude of GER impacts airways inflammation, as measured by the concentrations of H+ (pH) and NO in expired breath. The results of this trial should have a major impact on the understanding and treatment of GER in children with asthma.

描述（由申请人提供）： 哮喘儿童经常出现胃食管反流（GER），可以诱导支气管痉挛并增加气道反应性。患有哮喘的儿童经常用药物治疗GER，以抑制胃酸的产生。但是，这种治疗量昂贵，并且有未经证实的益处。该提案的主要目的是进行多站点，随机的临床试验，以检验以下假设：用兰索拉唑（一种批准的质子泵抑制剂）治疗GER将降低控制不良哮喘的儿童的加重频率。这项研究将包括300名接受吸入皮质类固醇治疗的哮喘儿童，6-16岁，由频繁症状，过度β激动剂使用或频繁恶化的症状定义不良。参与者将被随机分配给兰索拉唑或安慰剂六个月。 GER与哮喘症状的存在，严重程度和关系将通过24小时的食管pH监测确定，但是与治疗的随机分组不会受到GER的存在或严重程度的影响。主要结局措施是日记和访谈定义的哮喘患者加剧的参与者的比例。次要结局指标包括哮喘症状和控制分数，GER症状，肺功能和外科医疗保健接触。预定义的亚组分析将检查特定临床特征与对兰索拉唑的反应之间的关系。 治疗反应还将用剂量后血浆兰索浓度进行评估，并与CYP2C19，细胞色素P450途径和IL-1β（一种促炎性细胞因子）中的多态性有关。第三级研究将确定GER的大小如何影响气道炎症，如H+（pH）的浓度和无呼吸中的无。 该试验的结果应对哮喘儿童的GER的理解和治疗产生重大影响。