Phase 2 Study of Sildenafil for the Treatment of Lymphatic Malformations

项目摘要 淋巴管畸形(LMS)是淋巴管异常发育的局限性区域。 通常发生在儿童头部和颈部的淋巴系统。LMS被认为是 引起疼痛、溃疡、继发性疼痛等并发症的罕见或孤儿疾病 感染，其他器官的渗透，以及死亡。目前的治疗方法包括手术切除或 化学或物理破坏部分病变的方法。没有一种疗法是统一的 有效，所有这些都有发生重大不良事件的风险。我们最近目睹了几乎 接受西地那非口服治疗的儿童肺间质病变完全消失1例 肺动脉高压。我们随后评估了其他受试者 用西地那非改善疗效。这项临床研究试验的目标是记录益处或 缺乏西地那非治疗LMS的益处，并确定哪种类型的患者将受益 来自西地那非。这项研究是一项双盲安慰剂对照试验，涉及精确度 使用MRI记录与治疗或安慰剂相关的容量变化 分段技术。我们还将观察和记录西地那非的临床反应 或使用临床评估分数和调查的安慰剂。研究的结果应该确定 可能提示对西地那非治疗有有益反应的LM病变的特征。 在本试验中使用的剂量中，西地那非的副作用风险非常低。记录以下内容 LMS对西地那非的有效反应将促进对其的兴趣和能力 了解红斑狼疮的形成机制和治疗方法。

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.