PULSE ARGININE BUTYRATE IN SICKLE CELL DISEASE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 这项开放标签II期交叉研究将检验以下假设：1）脉冲式AB将诱导比HU单药治疗更高水平的Hb F，2）评估影响红细胞生成率的因素可能会识别出更有可能对HU + AB产生应答的患者亚组。 该研究仅对单独使用HU未缓解症状且基线Hb F至少为2%的患者开放。 患者将作为自己的对照。 将在接受6个月HU单药治疗的患者中评估临床事件和血液学因素。 然后添加AB治疗（4天，每月一次），并评估联合治疗的Hb F参数和临床事件。 如果发现两种药物的叠加效应，则试验可为选择最有可能从AB（除HU治疗外）获益的患者和III期试验的设计提供基础。 (This小规模试验不能作为FDA批准AB治疗镰状细胞病的关键试验。）

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 open-label Phase II cross-over study will test hypotheses that 1) Pulsed AB will induce higher levels of Hb F than HU alone, and 2) assessment of factors influencing erythropoietic rates may identify patient subsets who are more likely to respond to HU + AB. The study is open only to patients who have not had resolution of their symptoms with HU alone, and have a baseline Hb F of at least 2%. Patients will serve as their own controls. Clinical events and hematologic factors will be assessed in patients on HU alone for 6 months. AB therapy will then be added, (4 days, once/ month), and Hb F parameters and clinical events will be assessed on combined therapy. If additive effects are found with the two agents, the trial may provide a basis for selecting patients most likely to benefit from AB (in addition to HU therapy) and for design of Phase III trials. (This small trial will not serve as a pivotal trial for FDA approval of AB for treatment of sickle cell disease.)