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：（由申请人提供）淋巴管畸形 (LM) 是淋巴管异常发育的局部区域。淋巴系统，常见于儿童的头颈部。 LM 被认为是一种罕见或孤儿疾病，会导致并发症，包括疼痛、溃疡、继发感染、其他器官浸润和死亡。目前的疗法涉及手术切除或对部分病变进行化学或物理破坏的方法。没有一种疗法是一致有效的，并且所有疗法都有发生重大不良事件的风险。申请人报告了一名接受西地那非口服疗法治疗肺动脉高压的儿童的 LM 病变最近几乎完全消退。该临床研究试验的目的是记录西地那非治疗对 LM 的益处或缺乏益处，并确定哪种类型的患者会受益受益于西地那非。这项研究是一项双盲安慰剂对照试验，受试者为 40 名 6 个月至 10 岁的儿童，这些儿童患有较大的 LM（直径至少 3 厘米），接受基于体重的药物剂量治疗 20 周。该试验涉及通过使用 MRI 分割技术精确记录与治疗或安慰剂相关的体积变化。 20 周时，服用活性药物的患者将停用西地那非 12 周，而服用安慰剂的患者将有机会服用活性药物 20 周。主要终点是通过磁共振成像 (MRI) 评估的病灶体积变化，次要终点是医生和受试者评估。研究人员还将使用临床评估评分和调查来观察和记录对西地那非或安慰剂的临床反应。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有有益的反应。