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.

Public Health Relevance

There is no effective medical therapy for lymphatic malformations, which are localized areas of abnormal development of the lymphatic system that commonly occur in the head and neck of children. We have recently identified shrinkage of lymphatic malformations in several children treated with sildenafil oral therapy. The goal of this placebo-controlled trial is to document whether sildenafil is or is not an effective treatment for this orphan condition.

Agency
National Institute of Health (NIH)
Institute
Food and Drug Administration (FDA)
Type
Research Project (R01)
Project #
1R01FD004372-01A1
Application #
8612453
Study Section
Special Emphasis Panel (ZFD1-OPD-N (S1))
Project Start
2014-09-10
Project End
2018-08-31
Budget Start
2014-09-10
Budget End
2015-08-31
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Stanford University
Department
Dermatology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305