Propranolol vs Prednisolone for Infant Hemangiomas-A Clinical and Molecular Study

描述（由申请人提供）：本提案的长期目标是通过临床和分子基础研究，改善我们对婴儿症状性血管瘤（HOI）的管理，并提高我们对这种常见且有时危及生命的血管异常的理解。 血管瘤是最常见的儿科肿瘤，影响10%的婴儿。尽管他们的自然退化的预期过程中，医疗干预是指在10-25%的患者治疗显着的症状或预防严重的后遗症。HOI抑制疗法最常使用皮质类固醇治疗，但临床反应不可预测，并且这类药物的副作用很常见。最近的一份报告强调普萘洛尔作为HOI的替代治疗引发了极大的热情。虽然有趣，但普萘洛尔用于HOI的使用既没有得到证实也没有研究。本研究的具体临床目的是：1.评估进行一项前瞻性、随机化、医生盲法、多机构研究的可行性，以评价普萘洛尔与泼尼松龙（比较对照）治疗HOI的效果，并评估每种药物在1个月时的失败率。2.评估两种治疗的结果，包括由对治疗组不知情的医生完成的每月综合评价、使用创新的Voxar 3D体积平均软件在成像研究前后测量的躯体生长变化和病变体积变化。3.通过每月一次的父母生活质量调查、躯体生长的变化和由对治疗组不知情的医生完成的综合评估来评估每种治疗的耐受性。该提案还将在分子水平上分析HOI的生物学。将对治疗前、治疗期间和治疗后从受试者采集的尿液进行蛋白质组学和代谢组学分析，以确定对治疗的临床反应的预测因子。此外，将通过微阵列基因分析研究出于诊断目的切除的血管瘤组织，以鉴定与疾病程度相关或预测对治疗的反应的候选基因和RNA。 从这项可行性研究中获得的数据将用于确定是否需要更强大的研究来比较这两种治疗方法，并更好地阐明这种肿瘤进展背后的分子机制，指导进一步研究新的分子生物标志物和潜在的治疗靶点。 公共卫生相关性：这项研究比较了两种不同药物用于治疗血管瘤的效果和副作用，血管瘤是婴儿常见的良性血管肿瘤。血管瘤细胞的遗传组成的研究也被提出来提高我们对这种先天性异常的理解。

DESCRIPTION (provided by applicant): The long term objectives of this proposal are to improve our management of symptomatic hemangiomas of infancy (HOI) and to advance our understanding of this common, and sometimes life-threatening, vascular anomaly through a clinically and molecular based investigation. Hemangiomas are the most common pediatric neoplasm affecting 10% of infants. Despite their anticipated course of natural involution, medical intervention is indicated in 10-25% of patients to treat significant symptoms or to prevent serious sequelae. HOI warranting therapy are most frequently treated with corticosteroids but clinical response is unpredictable and side effects to this class of medications are common. A recent report highlighting propranolol as an alternative treatment of HOI has sparked much enthusiasm. Although intriguing, the use of propranolol for HOI has neither been verified nor studied. The specific clinical aims of this study are: 1. to assess the feasibility of conducting a prospective, randomized, physician-blinded, multi-institutional study to evaluate propranolol versus prednisolone, the comparative control, in treating HOI and to assess the failure rate of each medication at one month. 2. to assess the outcome of both treatments in terms of monthly comprehensive evaluations completed by a physician blinded to treatment arm, changes in somatic growth and changes in lesion volume measured on pre and post imaging studies using innovative Voxar 3D volumetric averaging software. 3. to assess tolerability of each treatment through monthly parental quality of life inventories, changes in somatic growth and comprehensive evaluations completed by a physician blinded to treatment arm. This proposal will also analyze the biology of HOI on molecular level. Proteomic and metabolomic analysis of urine collected from participants before, during and after treatment will be analyzed to identify predictors of clinical response to therapy. Additionally, hemangioma tissue excised for diagnostic purposes will be studied by microarray gene analysis to identify candidate genes and RNA that correlate with disease extent or that predict response to therapy. Data derived from this feasibility study will be used to determine if a more powerful study is indicated to compare these two treatments and to better elucidate the molecular mechanisms behind this neoplasm's progression, guiding further research into novel molecular biomarkers and potential therapeutic targets. PUBLIC HEALTH RELEVANCE: This study compares the effect and side effects of two different medicines used to treat hemangiomas, which are common benign blood vessel tumors that occur in infants. Studies of the genetic make-up of cells from hemangiomas are also proposed to improve our understanding of this congenital anomaly.