Chicago Sickle Cell Clinical Network

描述(由申请人提供)： 这项建议的目的是参与多中心(临床研究网络，CRN)治疗镰状细胞病(SCO)患者的治疗试验的设计和实施。我们建议进行两项临床试验，以提高疗效。1)比较达克根(DAC)和羟基脲(HU)对镰状细胞病临床症状的改善作用。尽管HU对症状性SCD有好处，但尽管接受HU治疗，仍有相当大比例的患者继续遇到问题。DAC已被证明在所有接受治疗的患者(HU无反应者和/或不耐受患者)中显著提高HBF水平并降低疾病严重程度的替代临床标记物。该研究设计为III期开放式随机试验，比较DAC 0.2 mg/kg皮下注射(SQ)和HU 15 mg/kg皮下注射(SQ)。这些剂量将一直增加，直到出现骨髓抑制。要比较这两个部门的主要终点将是危机频率。每支手臂100名患者的样本规模将提供90%的力量来检测危机频率33%的差异。这项建议的目的是参与设计和实施治疗镰状细胞病(SCD)患者的多个多中心治疗试验。2)根据患者所经历的疼痛类型，制定有效的疼痛治疗计划，并评估他们在一些多态基因，如mu受体、mdr1蛋白和细胞色素2D6中的基因变异性。我们将通过使用可靠的触摸屏计算机化工具来实现这一点，患者将使用该工具来获得对患者疼痛和他们对治疗的反应的全面评估。为了确定治疗变异是否有遗传基础，我们将使用一些多态基因来评估患者的基因变异，如Mu受体、mdr1蛋白和细胞色素2D6。(摘要结束)

DESCRIPTION (provided by applicant): 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 SCD, 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 phase III, 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 (SCD). 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. (End of Abstract)