Chicago Sickle Cell Clinical Network

本建议书的目的是参与多中心(临床)的设计和性能 CRN)治疗镰状细胞病(SCO)患者的治疗试验。我们 提出两个临床试验，以考虑其性能。1)比较Dacgen(DAC)和羟基脲 (HU)他们有能力减少镰状细胞病的临床症状。虽然胡在中国是一项福利 有症状的SCO，尽管接受了HU治疗，但仍有相当一部分患者继续遇到问题。 DAC已被证明可显著提高HBF水平，降低疾病的替代临床标志物 所有接受治疗的患者(HU无反应和/或不耐受患者)的严重程度。研究设计为第三阶段， DAC 0.2 mg/kg皮下注射(SQ)与HU 15 mg/kg皮下注射的随机开放试验。这些 剂量将会增加，直到出现骨髓抑制。之间要比较的主端点 两只手臂将是危机频发的地方。每只手臂100名患者的样本大小将提供90%的功率来检测 危机频率相差33%。这份提案的目的是参与设计和 镰状细胞病患者多中心治疗试验的效果 (上海合作组织)。2)根据患者的疼痛类型制定有效的疼痛治疗计划 经验，并评估它们在一些多态基因中的基因变异性，例如Mu 受体、mdr1蛋白和细胞色素2D6。我们将使用可靠的触摸屏来实现这一点 一种计算机化的工具，患者将使用它来获得对患者疼痛的全面评估，并 他们对治疗的反应。为了确定治疗差异是否有遗传基础，我们将评估 患者使用一些多态基因，如Mu受体，mdr1蛋白， 和细胞色素2D6。

The purpose of this proposal is to participate in the design and performance of multiple multicenter (Clinical Research Network, CRN) therapeutic trials for the treatment of patients with sickle cell disease (SCO). We propose two clinical trials to be considered for performance. 1) To compare dacogen (DAC)to hydroxyurea (HU) in their ability to decrease clinical symptoms of sickle cell disease. Although HU is a benefit in symptomatic SCO,a significant proportion of patients continue to encounter problems despite HU therapy. DAC has been shown to markedly increase HbF levels and decrease surrogate clinical markers of disease severity in all treated patients (HU non-responder and/or intolerant patients). The study design is a phaseIII, open lable, randomized trial comparing DAC 0.2mg/kg subcutaneously (sq) versus HU 15mg/kg. These doses will be increased until marrow depression occurs. The primary end-point to be compared between the two arms will be crisis frequency. A sample size of 100 patients per arm will provide 90% power to detect a 33% difference in crisis frequency. The purpose of this proposal is to participate in the design and performance of multiple multicenter therapeutic trials for the treatment of patients with sickle cell disease (SCO). 2) To develop an effective pain treatment plan for patients based upon the types of pain they experience., and evaluate them for genotypic variability in a number of polymorphic genes, such as mu receptor, MDR1 protein, and cytochrome 2D6. We will accomplish this by using a reliable touch screen computerized tool that the patient will use to obtain a comprehensive assessment of a patient's pain and their response to treatment. To determine if there is a genetic basis for treatment variation, we will evaluate patients for genotypic variability using a number of polymorphic genes, such as mu receptor, MDR1 protein, and cytochrome 2D6.