Chicago Sickle Cell Clinical Network

芝加哥镰状细胞临床网络

• 批准号: 7224149
• 负责人: JOSEPH DESIMONE
• 金额: $ 14.77万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-17 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7224149
• 关键词: Accounting; Adult; C-reactive protein; Cessation of life; Chicago; Clinical; Clinical Markers; Clinical Research; Clinical Treatment; Clinical Trials; Coagulation Process; Complement; Cutaneous; Cytochromes; Dacogen; Data; Decitabine; Disease Management; Dose; Double-Blind Method; End Point; Event; Fetal Hemoglobin; Fibrin fragment D; Frequencies; Functional disorder; Genes; Genetic; Hemoglobin; Hemolysis; Inflammation; Injection of therapeutic agent; Lactate Dehydrogenase; Lactate Dehydrogenases; Marrow; MeSH Thesaurus; Measurement; Measures; Melanocyte stimulating hormone; Mental Depression; Morbidity - disease rate; Narcotics; Normal Statistical Distribution; Numbers; Oral; Oral cavity; P-Glycoprotein; POMC gene; Pain; Patients; Performance; Pharmaceutical Preparations; Phase; Placebos; Pneumonia; Population; Population Study; Purpose; Quality of life; Randomized Controlled Clinical Trials; Rate; Research Design; Reticulocyte count; Review Committee; Safety; Sample Size; Score; Severity of illness; Sickle Cell; Sickle Cell Anemia; Standards of Weights and Measures; Stroke; Sum; Symptoms; System; Testing; Therapy Clinical Trials; Upper arm; Variant; Week; abstracting; acute chest syndrome; base; clinically significant; computerized tools; cytotoxic; day; design; experience; hydroxyurea; mortality; mu opioid receptors; pill; pre-clinical; response; subcutaneous; touchscreen; treatment planning; trial comparing

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)

描述（由申请人提供）： 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）患者的治疗试验的设计和实施。我们建议考虑两项临床试验的性能。1)比较达可金（DAC）和羟基脲（HU）减轻镰状细胞病临床症状的能力。尽管HU对症状性SCD有益，但仍有相当比例的患者在HU治疗后继续遇到问题。 DAC已显示在所有治疗患者（HU无应答和/或不耐受患者）中显著增加HbF水平并降低疾病严重程度的替代临床标志物。研究设计是一项比较DAC 0.2 mg/kg皮下（sq）与HU 15 mg/kg的III期、开放标签、随机试验。这些剂量将增加，直至发生骨髓抑制。两组之间比较的主要终点是危机频率。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治疗镰状细胞病（SCD）患者的多中心治疗试验的设计和实施。2)根据患者经历的疼痛类型为患者制定有效的疼痛治疗计划。并评估它们在许多多态性基因中的基因型变异性，如μ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及其对治疗的反应的全面评估。为了确定治疗变异是否存在遗传基础，我们将使用许多多态性基因（如mu受体、MDR 1蛋白和细胞色素2D 6）评价患者的基因型变异性。(End摘要）