CHILDHOOD ASTHMA PREVENTION STUDY (CAPS) FOR PACRN

PACRN 儿童哮喘预防研究 (CAPS)

• 批准号: 6669158
• 负责人: ROBERT S ZEIGER
• 金额: $ 20.67万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6669158
• 关键词: antiantibody; asthma; child (0-11); clinical research; clinical trials; cooperative study; disease /disorder prevention /control; human subject; human therapy evaluation; immunoglobulin G; longitudinal human study; monoclonal antibody; placebos; respiratory disorder chemotherapy

Asthma is the most common chronic respiratory disease of childhood with prevalence, morbidity and mortality increasing in epidemic proportions throughout the world despite better diagnosis and improved anti-inflammatory treatment. Recombinant humanized monoclonal anti-IgE is the most promising immunomodulatory agent available today to non-specifically modulate IgE, the major effector molecule in allergic asthma. Anti-IgE reduces free IgE and IgE receptors more than 95 percent, improves asthma symptoms, lung function, and reduces prn bronchodilator use and corticosteroid use in moderate to severe persistent allergic asthma in adolescents and adults. Proposed here are two projects, each prospective, randomized, masked, and placebo-controlled, to evaluate the effectiveness and safety of anti-IgE in primary and secondary asthma prevention in children. Proposal number 1 or primary asthma prevention will determine whether anti-IgE can prevent the development of asthma in 232 high-risk infants 1 to 2 years of age with atopic dermatitis, food allergy, or allergic rhinitis and specific IgE and a parental history of atopy. Patients will be randomized into anti-IgE or placebo groups, given bimonthly subcutaneous injections of anti-IgE or placebo, and followed for the development of asthma for 3 years. Secondary objectives include determination if anti-IgE compared to placebo differ with respect to (1) the onset of at least mild persistent asthma, (2) lung impedance and bronchial responsiveness determined by impulse oscillation, (3) skin test reactivity and markers of inflammation, (4) effect on atopic disorders, and (5) long-term safety and growth. Proposal number 2 or secondary asthma prevention will determine the effectiveness of anti-IgE compared to placebo to reduce inhaled corticosteroid (ICS) requirements (steroid sparing) in 140 children 5-12 years of age with moderate to severe persistent allergic asthma requiring ICS. Subjects will be randomized into anti-IgE or placebo groups, given bimonthly subcutaneous injections of anti-IgE or placebo for 1 year, and followed in two phases. During Phase I or the 12-week adjunctive phase, patients will maintain their stable dose of ICS, and during Phase II or the 40-week ICS withdrawal phase, subjects will have their ICS reduced according to protocol. The efficacy and safety of anti- IgE therapy versus placebo will be compared in terms of (1) the reduction in ICS dose measured by real time monitoring of ICS use electronically (primary aim), (2) asthma symptom scores, medication use, and peak expiratory flow levels monitored electronically, (3) levels of lung function and bronchial responsiveness, (4) humanistic and pharmacoeconomic measures, (6) skin test reactivity and markers of inflammation, (7) somatic growth, and (8) adverse events.

哮喘是儿童期最常见的慢性呼吸道疾病，尽管诊断和改善了抗炎治疗，但全世界流行比例的流行率和死亡率增加。 重组人性化的单克隆抗IgE是当今可用于非特异性调节IgE的最有希望的免疫调节剂，这是过敏性哮喘中的主要效应分子。抗IgE可降低自由IgE和IgE受体超过95％，可改善哮喘症状，肺功能，并减少PRN支气管扩张剂的使用，皮质类固醇在中度至重度持续的持续过敏性哮喘中使用，在青少年和成人中。 这里提出的两个项目，每个项目，每个项目，随机，掩盖和安慰剂对照，以评估儿童抗IGE的有效性和安全性。提案数字1或原发性哮喘预防将确定抗IGE是否可以防止232名高危婴儿1至2岁的哮喘发育，而特应性皮炎，食物过敏或过敏性鼻炎和特定的IGE以及特定的IGE以及ATOPY的父母历史。 将患者随机分为抗IGE或安慰剂组，给定两次皮下注射抗IGE或安慰剂，然后进行3年哮喘的发育。 次要目标包括确定与安慰剂相比是否相对于（1）至少轻度持续性哮喘的发作，（（2）通过脉冲振荡确定的肺阻抗和支气管反应能力，（3）皮肤测试的反应性和炎症标记，（4）对植物疾病的影响，以及（4）对型疾病的影响，以及（5）长期安全和（5）长期安全。与安慰剂相比，预防2号或继发性哮喘的提案将确定抗IGE的有效性，以减少140名5-12岁儿童中吸入的皮质类固醇（ICS）需求（类固醇保留），中度至重度持续性过敏性哮喘需要ICS。 受试者将被随机分为抗IGE或安慰剂组，并给予双月皮下注射抗IGE或安慰剂1年，然后分为两个阶段。 在第一阶段或12周的辅助阶段，患者将保持其稳定的ICS剂量，在II期或40周的ICS戒断阶段，受试者将根据方案减少ICS。 （1）通过以电子方式进行实时监测ICS剂量测量的ICS剂量的降低（主要目的），（2）哮喘症状得分，药物使用和峰值呼气水平以电子方式监测，（3）肺部功能性验证性，（4）人类验证性，（4），（3），（3），将对抗IGIN疗法与安慰剂的安全性与安慰剂的安全性进行比较（主要目的），（2）哮喘症状得分，药物使用和峰值呼气流量水平，以电子方式监测，（3）肺部功能性验证性，（3），（3）具有人性化的人，（3），（4）人类的人性化，（4），（4）（4）（4）（4），（4）（4）（4）（4）（4）（4）（4）（4）（4）炎症，（7）体细胞生长和（8）不良事件的反应性和标记。