Study of Acid Reflux Therapy for Children with Asthma

儿童哮喘胃酸反流治疗研究

• 批准号: 7288749
• 负责人: Janet T. Holbrook
• 金额: $ 45.37万
• 依托单位: JOHNS HOPKINS 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 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7288749
• 关键词: Acids; Adrenal Cortex Hormones; Adverse event; Age-Years; Agonist; Asthma; Breathing; Bronchial Spasm; CYP2C19 gene; Child; Clinical; Clinical Trials Data Monitoring Committees; Communication; Cytochrome P450; Data; Data Analyses; Data Collection; Data Coordinating Center; Disease; Documentation; Dose; Electronics; Esophageal; Frequencies; Gastric Acid; Gastroesophageal reflux disease; Genetic Polymorphism; Grant; Healthcare; Hour; Inflammatory; Informed Consent; Interleukin-1 beta; Interview; Label; Lansoprazole; Lead; Leadership; Manuals; Masks; Measures; Monitor; Online Systems; Operative Surgical Procedures; Outcome Measure; Participant; Pathway interactions; Patients; Performance; Pharmaceutical Preparations; Placebos; Plasma; Procedures; Production; Protocols documentation; Proton Pump Inhibitors; Publications; Random Allocation; Randomized; Randomized Clinical Trials; Reflux; Reporting; Research Ethics Committees; Research Infrastructure; Research Personnel; Respiratory physiology; Score; Severities; Site; Subgroup; Symptoms; System; Testing; Training; Variant; airway inflammation; base; cytokine; data management; design; diaries; follow-up; knowledge base; quality assurance; response; symposium; web based interface

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）： 胃食管反流 (GER) 在哮喘儿童中很常见，可诱发支气管痉挛并增加气道反应性。患有哮喘的儿童通常会使用抑制胃酸产生的药物来治疗 GER。然而，这种治疗方法价格昂贵，而且疗效尚未得到证实。该提案的主要目的是进行一项多中心、随机、临床试验，以检验以下假设：用兰索拉唑（一种已批准的质子泵抑制剂）治疗 GER 将降低哮喘控制不佳的儿童病情恶化的频率。该研究将包括 300 名接受吸入皮质类固醇治疗的 6-16 岁哮喘儿童，这些儿童因症状频繁、过度使用 β 受体激动剂或频繁恶化而控制不佳。参与者将被随机分配接受兰索拉唑或安慰剂治疗，为期六个月。 GER 的存在、严重程度以及与哮喘症状的关系将通过 24 小时食道 pH 监测来确定，但治疗的随机化不会受到 GER 的存在或严重程度的影响。主要结果指标是根据日记和访谈确定的哮喘恶化的参与者比例。次要结果指标包括哮喘症状和控制评分、GER 症状、肺功能和计划外的医疗保健接触。预先定义的亚组分析将检查特定临床特征与兰索拉唑反应之间的关系。 治疗反应也将通过给药后 3 小时血浆兰索拉唑浓度进行评估，并与 CYP2C19、细胞色素 P450 途径和 IL-1 beta（一种促炎细胞因子）的多态性相关。第三项研究将确定 GER 的大小如何影响气道炎症，通过呼气中 H+ (pH) 和 NO 的浓度来测量。 该试验的结果将对哮喘儿童 GER 的理解和治疗产生重大影响。