TCD Ultrasound of Subjects Enrolled in Baby HUG

描述(由申请人提供)： 婴儿TCD是婴儿拥抱初始阶段的拟议辅助研究，婴儿拥抱是一项由NHLBI/NIH(合同号：N01-HB-07160)。在婴儿拥抱中，患有镰状细胞病(SCD)的婴儿(12-17个月大)将被随机分为羟基尿素(HU)或安慰剂，并跟踪观察24个月。在被研究的儿童中，HU对中枢神经系统的影响引起了广泛的兴趣。中风发生在1岁以后，有证据表明，在一些患者中，脑血管疾病的过程开始得很早。镰状细胞病的合作研究记录了2-6岁年龄组发生中风的高风险。这项辅助研究建议通过使用经颅多普勒(TCD)超声作为中风风险的生物标记物来探索HU可能如何发挥作用。这项拟议的研究将在基线和研究结束时对40名接受婴儿拥抱的儿童进行TCD。TCD已被证明在评估2-16岁SCD儿童的卒中风险方面非常有用，并且处于NHLBI基于STOP研究推荐的一级卒中预防范例的中心。如果中风风险可以在更早的阶段被检测到(即，比2-16岁的受试者更年轻)，那么医生将能够在疾病的早期阶段提供预防性治疗。治疗前和治疗24个月后进行经颅多普勒超声检查。TCD的性能和读数将得到集中控制和停止一致。提倡者有婴儿经颅多普勒超声的经验，这是父母研究的目标年龄。治疗前后比较HU组与对照组的TCD变化。此外，提倡者还可以访问400多名2-4岁儿童的数据，这些儿童的年龄范围从20世纪90年代中期到后期的停止筛查计划开始。由于这些患者没有接受HU或输血，这个数据集将被用来估计不接受HU治疗的高中风风险的患病率，并可以与婴儿拥抱中的HU组进行比较，这为分析增加了另一个重要的比较维度。尽管父母研究设计的样本量故意较小，但通过Baby TCD可以检测到治疗结束时高危患者患病率的巨大差异。

DESCRIPTION (provided by applicant): Baby TCD is a proposed ancillary study to the initial phase of Baby HUG, a multicenter clinical trial funded by NHLBI/NIH (Contract No. N01-HB-07160). In Baby HUG, infants (12-17 months old) with sickle cell disease (SCD) will be randomized to either hydroxyurea (HU) or placebo and followed for 24 months. There is broad interest in the effect of HU on the central nervous system in the children being studied. Stroke occurs after age 1 year and there is evidence that the process of cerebrovascular disease starts very early in some patients. The Cooperative Study of Sickle Cell Disease documented a high risk of incident stroke in the 2-6 year age group. This ancillary study proposes to explore how HU might work by using transcranial Doppler (TCD) ultrasound as a biomarker of stroke risk. The proposed study will perform TCD on the 40 children in Baby HUG at baseline and at end of study. TCD has proven very useful in estimation of stroke risk in children with SCD ages 2-16 years, and is at the center of a paradigm of primary stroke prevention recommended by NHLBI based on the STOP study. If stroke risk could be detected at an earlier stage (i.e., younger than the 2-16 year-old subjects in STOP), then physicians would be able to provide preventive treatment at an earlier stage of the disease. TCD will be performed before and after 24 months of treatment. TCD performance and reading will be centrally controlled and STOP-consistent. The proposers have experience in TCD of infants, the age targeted by the parent study. TCD will be compared between HU and control groups, before and after treatment. In addition, the proposers have access to data from over 400 children in the 2-4 year age range from the STOP screening program performed in the mid- to late 1990s. Since these patients were not on HU or transfusion this dataset will be used to give an estimate of the prevalence of high stroke risk without HU treatment, and can be compared to the HU group in Baby HUG, adding another important comparative dimension to the analyses. Although the sample size is purposely small as designed by the parent study, large differences in the prevalence of high-risk patients at the end of treatment could be detected by Baby TCD.