Chicago Sickle Cell Clinical Network

本提案的目的是参与多中心（临床） 研究网络，CRN）治疗镰状细胞病（SCO）患者的治疗试验。我们 建议考虑两项临床试验的性能。1)达可根（DAC）与羟基脲的比较 (HU)减少镰状细胞病临床症状的能力。虽然胡是一个好处， 症状性SCO，尽管HU治疗，仍有相当比例的患者继续遇到问题。 DAC已被证明可显著增加HbF水平并降低疾病的替代临床标志物 所有治疗患者（HU非应答者和/或不耐受患者）的严重程度。研究设计为III期， 比较DAC 0.2 mg/kg皮下（sq）与HU 15 mg/kg的开放标签、随机试验。这些 将增加剂量直至发生骨髓抑制。两组之间比较的主要终点 两个武器将是危机的频率。每组100例患者的样本量将提供90%的把握度来检测 危机频率的33%差异。本提案的目的是参与设计， 治疗镰状细胞病患者的多中心治疗试验的性能 （SCO）。2)根据患者的疼痛类型制定有效的疼痛治疗计划， 经验。并评估它们在许多多态性基因中的基因型变异性，如mu 受体、MDR 1蛋白和细胞色素2D 6。我们将通过使用可靠的触摸屏来实现这一点 计算机化工具，患者将使用该工具来获得对患者疼痛的全面评估， 他们对治疗的反应。为了确定治疗变异是否有遗传基础，我们将评估 使用许多多态性基因，如μ受体，MDR 1蛋白， 细胞色素2D 6

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.