DOSE OF INHALED CORTICOSTEROID WITH EQUISYSTEMIC EFFECTS (DICE)--PILOT STUDY

在正式方案开始之前，吸入剂量 具有等系统效应的皮质类固醇（DICE），一项初步研究描述了 使用倍氯米松（BDP）以84 mcg/喷进行以下操作 氟替卡松（FP）44 mcg/喷。 大约5名受试者将 在六个中心（最终总数为27个）进行研究， 关于吸入的 在轻度-中度哮喘受试者中使用皮质类固醇（ICS）， 确保所有技术在每个中心正常工作， 启动正式协议。 此外，发展局和粮食计划署 我们将首先确定肾上腺抑制的剂量 演示。 初步研究的结果将指导给药、采样 正式协议的规模和技术。 背景和理由 吸入性皮质类固醇（ICS）被推荐用于哮喘 比以前更频繁地和以更高剂量治疗）。 由于皮质类固醇具有多种潜在的全身不良反应， 必须能够比较不同的可吸入的 类固醇和递送系统的全身作用， 作为哮喘治疗的有效性。 虽然几种吸入性类固醇（ 不同的体外效力和药代动力学特征）和 目前可获得吸入递送系统， 将在未来几年引入，体内全身效应数据 比较这些吸入类固醇和输送系统缺乏。 在这项DICE研究中，我们提出了一个实验范式，其中吸入 类固醇和递送系统的特征在于全身性 因此，“等全身”剂量随后可以在 未来的疗效试验，包括哮喘临床研究网络 （ACRN）题为“测量吸入性皮质类固醇”的疗效试验 功效”（MICE）。 在DICE试验中，将使用肾上腺抑制 作为全身吸收的主要指标。 作为网络，我们 承认儿童的生长和结缔组织参数 是系统吸收的重要指标，但由于缓慢的 这些结果指标的变化率， 快速评估。 因此，我们建议使用血浆皮质醇 曲线（随时间推移测定），其是灵敏且可重现的 基础肾上腺功能指标作为我们全身类固醇指标 吸收 尿皮质醇排泄将是次要指标， 肾上腺抑制 骨重建的标志物， 类固醇，特别是血清骨钙素和尿N端肽， 也将作为全身吸收的次要指标 及效果

Prior to the initiation of the formal protocol, Dose of Inhaled Corticosteroids with Equisystemic Effect (DICE), a pilot study described below is to be performed employing beclomethasone (BDP) at 84 mcg/puff and fluticasone (FP) at 44 mcg/puff. Approximately five subjects will be studied at each of six centers (final total of 27) to obtain preliminary data on the variability of systemic absorption of inhaled corticosteroids (ICS) among subjects with mild-moderate asthma and to ensure all techniques are working appropriately at each center prior to initiation of the formal protocol. Additionally, for both BDP and FP we will establish at what dose adrenal suppression is first demonstrated. The results of the pilot study will guide dosing, sample size and techniques for the formal protocol. Background and Rationale Inhaled corticosteroids (ICS) are being recommended for use in asthma treatment both more frequently and at higher doses than previously). Since corticosteroids have multiple potential adverse systemic effects, it is essential to be able to compare the different available inhaled steroids and delivery systems with respect to both systemic effects and efficacy as an asthma treatment. While several inhaled steroids (with differing in vitro potencies and pharmacokinetic characteristics) and inhaled delivery systems are presently available, and others expected to be introduced in coming years, in vivo systemic effects data comparing these inhaled steroids and delivery systems are lacking. In this DICE study we propose an experimental paradigm in which inhaled steroids and delivery systems are characterized in terms of systemic effects so that "equi-systemic" doses can be subsequently compared in future efficacy trials, including the Asthma Clinical Research Network (ACRN) efficacy trial entitled "Measuring Inhaled Corticosteroid Efficacy" (MICE). In the DICE trial, adrenal suppression will be used as the primary index of systemic absorption. As a network we acknowledge that growth in children and connective tissue parameters are important indicators of systemic absorption, but due to the slow rate of change in these outcome measures, they do not lend themselves to rapid evaluation. We therefore propose to use plasma cortisol profiles (determined over time) which are a sensitive and reproducible indicator of basal adrenal function as our index of systemic steroid absorption. Urine cortisol excretion will be a secondary measure of adrenal suppression. Markers of bone remodelling which are sensitive to steroids, specifically serum osteocalcin and urinary N-telopeptide, will also be incorporated as secondary indices of systemic absorption and effect.