Timolol for the Prevention of Proliferation of Infantile Hemangioma (TiPPIH Trial)

NCT ID: NCT01434849

Last Updated: 2016-11-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2016-04-30

Brief Summary

The purpose of this trial is to see if a topical beta blocker is effective in preventing the proliferation of infantile hemangioma.

Detailed Description

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.

Conditions

Infantile Hemangioma; Very Low Birth Weight Infants

Keywords

infantile hemangioma; very low birth weight infants; premature infants

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Timolol

Application of 1-2 drops of Timolol maleate 0.5% ophthalmic aqueous solution to hemangioma twice daily.

Group Type: EXPERIMENTAL

topical 0.5% Timolol maleate

Intervention Type: DRUG

topical 0.5% Timolol aqueous solution, 1-2 drops to cover the hemangioma, twice daily

Placebo

Application of 1-2 drops of placebo gel twice daily to hemangioma.

Group Type: PLACEBO_COMPARATOR

Control (placebo) group

Intervention Type: DRUG

Aqueous placebo, 1-2 drops to cover the hemangioma, twice daily

Interventions

topical 0.5% Timolol maleate

topical 0.5% Timolol aqueous solution, 1-2 drops to cover the hemangioma, twice daily

Intervention Type: DRUG

Control (placebo) group

Aqueous placebo, 1-2 drops to cover the hemangioma, twice daily

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Babies admitted to NICU or seen in follow clinic that have a diagnosis of hemangioma that is verified by Principal Investigator (PI) or Co-Principal Investigators.

Exclusion Criteria

• Babies with PHACES (Posterior fossa, Hemangioma, Arterial lesions, Cardiac abnormalities, Eye abnormalities) syndrome
• Babies with cardiac conditions that may predispose to heart block
• Babies with persistent hypoglycemia
• Babies on medications that may interact with beta blockers
• Babies who are hemodynamically unstable and are requiring pressors to maintain blood pressure
• Babies who are on systemic corticosteroid therapy

• Maximum Eligible Age: 6 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alice K. Gong

OTHER

Sponsor Role: lead

Responsible Party

Alice K. Gong

Professor of Pediatrics

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Alice K Gong, M.D.

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center at San Antonio

Alice K Gong, MD

Role: STUDY_DIRECTOR

University of Texas

Locations

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Countries

United States

Other Identifiers

HSC20110333H

Identifier Type: -

Identifier Source: org_study_id