Phase 2 Study of Sildenafil for the Treatment of Lymphatic Malformations

描述：(申请人提供) 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被认为是一种罕见的或孤儿疾病，会导致包括疼痛、溃疡、继发感染、其他器官渗透和死亡在内的并发症。目前的治疗方法包括手术切除或对部分病变进行化学或物理破坏。没有一种疗法是统一有效的，而且所有疗法都有发生重大不良事件的风险。申请人报告了最近一例接受西地那非口服治疗的儿童的肺间质病变几乎完全消失。这项临床研究试验的目标是记录西地那非治疗LMS的益处或无益处，并确定哪种类型的患者将 受益于西地那非。 这项研究是一项双盲安慰剂对照试验，涉及40名6个月至10岁患有大(至少3厘米直径)LMS的儿童，以体重为基础的药物剂量治疗20周。这项试验使用MRI分割技术精确记录了与治疗或安慰剂相关的体积变化。在20周时，服用活性药物的患者将停止使用西地那非12周，而服用安慰剂的患者将有机会服用20周的活性药物。主要终点是通过磁共振成像(MRI)与医生和受试者的次要终点评估的病变体积的变化。研究人员还将使用临床评估分数和调查来观察和记录西地那非或安慰剂的临床反应。这项研究的结果应该确定肺组织病变的特征，这可能表明对西地那非治疗有有益的反应。

DESCRIPTION: (provided by the applicant) 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. The applicant reported a recent almost complete resolution of a LM lesion in a child who was treated with sildenafil oral therapy for pulmonary arterial hypertension. 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 of 40 children aged 6 months to 10 years with large (at least 3 cm diameter) LMs to be treated for 20 weeks with a weight-based dose of the medication. The trial involves precise documentation of volume changes associated with therapy or placebo by using MRI segmentation techniques. At 20 weeks, those on active drug are to discontinue sildenafil for 12 weeks while those on placebo are offered the opportunity to take the active medication for 20 weeks. The primary endpoint is change in lesion volume as evaluated by magnetic resonance imaging (MRI) with secondary endpoints of physician and subject evaluations. The investigators 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.