Phase 2 Study of Sildenafil for the Treatment of Lymphatic Malformations

西地那非治疗淋巴管畸形的 2 期研究

基本信息

批准号：
9446776
负责人：
Anna Lee Bruckner
金额：
$ 8.68万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-10 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9446776
关键词：
Phase Study Sildenafil Treatment Lymphatic

项目摘要

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.

描述：（申请人提供）淋巴畸形（LMS）是异常发展的局部区域通常发生在儿童头部和颈部的淋巴系统。 LMS被认为是一种罕见或孤儿疾病，会引起并发症，包括疼痛，溃疡，继发感染，其他器官的浸润以及死亡。当前的疗法涉及一部分病变的化学或物理破坏方法的手术切除或方法。没有疗法均匀有效，所有疗法都有重大不良事件的风险。申请人报告说，最近在接受西地那非口服治疗治疗肺动脉高压治疗的儿童中几乎完全解决了LM病变。这项临床研究试验的目的是记录西地那非治疗对LMS的好处或缺乏，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，对40名6个月至10岁的儿童进行了较大（至少3厘米）LMS的儿童，并通过基于体重的药物治疗20周。该试验涉及使用MRI分割技术的精确文献与治疗或安慰剂相关的体积变化。在20周的时候，那些活跃药物的人将停止西地那非12周，而安慰剂上的人有机会服用活性药20周。主要终点是通过磁共振成像（MRI）评估的病变体积变化，并具有医师和受试者评估的继发终点。研究人员还将使用临床评估分数和调查观察并记录对西地那非或安慰剂的临床反应。该研究的结果应确定LM病变的特征，这可能表明对西地那非治疗有益反应。