Phase 2 Study of Sildenafil for the Treatment of Lymphatic Malformations

项目摘要 淋巴管畸形（LM）是局部区域的异常发展， 淋巴系统，通常发生在头部和颈部的儿童。LM被认为是 罕见或罕见疾病，引起并发症，包括疼痛、溃疡、继发性 感染，其他器官的渗透，和死亡。目前的治疗方法包括手术切除或 化学或物理破坏病变部分的方法。没有一种治疗方法是统一的 有效，并且都有发生重大不良事件的风险。我们最近目睹了几乎 1例接受西地那非口服治疗的儿童LM病变完全消退， 肺动脉高压我们随后评估了其他受试者， 西地那非改善了本临床研究试验的目的是记录获益或 西地那非治疗LM缺乏获益，并确定哪种类型的患者将获益 来自西地那非。本研究是一项双盲安慰剂对照试验， 使用MRI记录与治疗或安慰剂相关的体积变化 分割技术我们还将观察和记录西地那非的临床反应 或安慰剂使用临床评估分数和调查。研究结果应确定 LM病变的特征，这可能表明对西地那非治疗的有益反应。 在本试验中使用的剂量中，西地那非的副作用风险非常低。文件的一个 LMs对西地那非的有效反应将加速对以下方面的兴趣和能力： 了解LM的形成和治疗机制。

Project Summary Lymphatic malformations (LMs) are localized areas of abnormal development of the lymphatic system that commonly occur in the head and neck of children. LMs are considered a rare or orphan disease which causes complications including pain, ulceration, secondary infection, infiltration of other organs, and death. Current therapies involve surgical excision or methods of chemical or physical destruction of portions of lesions. No therapies are uniformly effective and all have the risk of significant adverse events. We recently witnessed almost complete resolution of a LM lesion in a child who was treated with sildenafil oral therapy for pulmonary arterial hypertension. We have subsequently evaluated additional subjects who improved with sildenafil. The goal of this clinical research trial is to document the benefit or absence of benefit of sildenafil therapy for LMs and identify which type of patient will benefit from sildenafil. This study is a double-blind placebo-controlled trial which involves precise documentation of volume changes associated with therapy or placebo by using MRI segmentation techniques. We will also observe and document the clinical response to sildenafil or placebo using clinical evaluation scores and surveys. The results of the study should identify characteristics of LM lesions which may suggest a beneficial response to sildenafil therapy. Sildenafil has very low risk of side effects in the dosage used in this trial. Documentation of an effective response of LMs to sildenafil will accelerate the interest in, and the ability to understand, the mechanisms of LM formation and treatment.