SUBCUTANEOUS INTERFERON-GAMMA FOR TB/HIV

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定是研究者机构。本研究的目的是随机分配结核病（TB）患者，根据本方案接受重组干扰素-γ（rIFN-g）200 μ g皮下注射，每周3次，持续4个月，或接受同时资助的研究（TB和AIDS的宿主应答）（NIH 059832; SPID编号826）的两个随机化组（IFN气雾剂或安慰剂）之一的治疗。InterMune为这项研究以及结核病和艾滋病的宿主反应免费提供rIFN-g。由于NIH资助的方案不能改变以增加第三个治疗组，因此本方案将提供额外患者的随机化至皮下组，以使皮下IFN与气雾剂和安慰剂组的无偏倚比较成为可能。特别是，待检验的假设是给药类型（皮下vs.气雾剂）是否影响肺结核的免疫和纤维化功能终点。 具体目的如下：1）随机分配患者以如该方案中所述接受皮下IFN-g，对比NIH 059832中的气雾剂或安慰剂。本研究将在轻度至中度肺结核患者中进行，以评估每周三次皮下注射200 mcg rIFN-g 1b 16周+短期直接观察治疗（DOTS）的疗效。TB患者将以2：1的随机化比例进行分配，即每1例患者分配至该单独子研究，就有2例患者分配至NIH方案。2)评价rIFN-g治疗前后的支气管肺泡灌洗液细胞和PBMC，以表征Th 1应答的诱导。3)通过检查TGF-β系统和肺功能基因组研究，确定rIFN-g与改善双侧空洞性TB纤维化和组织破坏相关的体内分子效应

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. The purpose of this study is to randomize tuberculosis (TB) patients to receive recombinant interferon-gamma (rIFN-g) 200 micrograms subcutaneously 3 times a week for 4 months on this protocol or to receive treatment on one of the two randomized arms (aerosol IFN or placebo) of the concurrent funded study, Host Response to TB and AIDS (NIH 059832; SPID no. 826). InterMune is providing the rIFN-g free of charge for this study as well as for Host Response to TB and AIDS. Because the NIH-funded protocol cannot be altered to add a third treatment arm, this protocol will provide the randomization of the additional patients to the subcutaneous arm to enable an unbiased comparison of the subcutaneous IFN to the aerosol and placebo arm. In particular, the hypothesis to be tested is whether type of administration (subcutaneous vs. aerosol) affects the endpoints of immune and fibrotic functions in pulmonary TB. The specific aims are as follows: 1) Randomize patients to receive subcutaneous IFN-g as described in this protocol vs. aerosol or placebo in NIH 059832. This study will be conducted in minimal to moderate pulmonary TB patients to evaluate the efficacy of 16 weeks of 200 mcg rIFN-g 1b by subcutaneous injection three times a week plus Directly Observed Therapy Short Course (DOTS). TB patients will be allocated in a 2:1 randomization that allocates 2 patients to the NIH protocol for every 1 patient to this separate substudy. 2) Evaluate bronchoalveolar lavage cells and PBMCs before and after rIFN-g treatment to characterize the induction of a Th1 response. 3) Determine the in vivo molecular effects of rIFN-g that relate to amelioration of fibrosis and tissue destruction in bilateral, cavitary TB by examining the TGF-b system and pulmonary functional genomic studies