Trial Information

Phase 1 Study of Topical Beta Blocker to Prevent the Proliferative Stage of Infantile Hemangioma

Infantile hemangiomas (IH) are among the most common, benign vascular tumors of infancy with
an estimated prevalence of 4-5% of the population. IH are not found at birth but become
evident within the first few weeks of life. They are characterized by a rapid proliferative
phase that can last up to 4-6 months or longer and then a period of minimal or absent growth
before an involutive phase where they may resolve with minimal or no scarring over multiple
years. Although frequently thought of as benign lesions, hemangiomas can occur in locations
to cause functional impairment of vital organs, can lead to ulcerations, scarring or
disfigurement, and can lead to life-threatening complications. Management of these
problematic IH includes laser, long-term systemic corticosteroids, interferon, Vincristine,
surgery, and most recently systemic propranolol. Pulsed-dye laser is the only treatment
approved by the FDA; it has been useful for superficial hemangiomas but has little effect on
subcutaneous or deep-seated hemangiomas. The proposed therapeutic effects of propranolol are
vasoconstriction, decreased expression of vascular endothelial growth factor (VEGR) and
basic fibroblast growth factors (bFGF) genes through downregulation of Raf/mitogen-activated
protein kinase pathway, and apoptosis of capillary endothelial cells. For periorbital
lesions that may cause amblyopia or anisometropia, topical Timolol has been reported to be
of benefit. There is one retrospective review that is proof of concept that shows that
topical timolol is safe and effective treatment for 6 cases of IH.

The advantage of a topical therapy is the decreased risk of systemic side effects compared
with oral or intravenous administration. The disadvantage is that limited penetration may
preclude effectiveness for the thicker or deeper lesions.

Being of low birth weight as well as prematurity are known risk factors for IH. In the
premature infant development clinic at the University of Texas Health Science Center in San
Antonio infants less than 1500 grams birth weight are followed for three years following
discharge from the Newborn Intensive Care Unit (NICU); approximately 16% of these infants
have hemangiomas. Therefore the investigators find it reasonable to start treatment with a
topical beta blocker at an early stage of hemangioma to prevent the growth and proliferation
and hence the possible severe effects associated with growth and thus impairment of vital
organs/tissues.