TYPE 1 DIABETES GENETICS CONSORTIUM

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a single-center, randomized, open-label, dose-ranging study to characterize the effects of different doses/regimens of aerosolized Baxter/Arriva rAAT therapy on lower respiratory epithelial lining fluid (ELF) AAT enzyme levels, AAT human neutrophil elastase complex concentration, inflammatory mediators, and cytology, and to evaluate safety and immunogenicity of different doses/regimens in subjects with a diagnosis of severe AAT deficiency. A minimum of 15 qualified subjects will be enrolled in the study. The study drug will be administered by inhalation. The delivery device to be used in this study will be the AeroEclipse¿- Breath-Actuated Nebulizer (BAN; Truedell Medical International, Inc, London, Ontario, Canada), in conjunction with the PARI PRONEB¿- ULTRA compressor. In tests with the Baxter/Arriva rAAT solution, the mass median aerodynamic diameter (MMAD) for this nebulizer ranged from 1.4 to 2.3 microns. For a 200 mg dose (nebulizer charge), the nebulizer output averaged 47%.ii