Symptoms and General Pathology

All Conditions

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Neoplasms

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Skin and Connective Tissue Diseases

Body Weight

Premature Birth

Birth Weight

Hemangioma

Hemangioma, Capillary

Port-Wine Stain

Neoplasms, Vascular Tissue

Neoplasms by Histologic Type

Congenital Abnormalities

Skin Abnormalities

Skin Diseases

Pharmaceutical Solutions

All Drugs and Chemicals

Anti-Arrhythmia Agents

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Adrenergic beta-Antagonists

Timolol

Maleic acid

Adrenergic Agents

Adrenergic Antagonists

Neurotransmitter Agents

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

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

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

topical 0.5% Timolol maleate

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

Control (placebo) group

Alice K Gong, M.D.

Alice K Gong, MD

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

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

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

Many participants did not complete trial so there is not enough data to share.

hemangioma once detected will be measured and photographed. Measurements and photographs will be obtained every 2 weeks while the patient is in hospital and monthly after discharged until end point of 6 months.

Difference in color of the hemangioma of the treatment group versus control group

More significant Retinopathy of Prematurity findings between treatment group versus control group

Frequency of adverse events (e.g. hypotension, behavioral changes, etc.) collected by investigator and reported by NICU staff and parents.

Alice K. Gong

Professor of Pediatrics

Half of the enrolled subjects (intervention group) will receive topical 0.5% Timolol.

Aqueous placebo, 2-3 drops to cover the hemangioma, twice daily

topical 0.5% Timolol aqueous solution, 2-3 drops to cover the hemangioma, twice daily

topical 0.5% Timolol

Alfons L. Krol, M.D.

The purpose of this study is to learn about a new potential use for topical timolol 0.5% aqueous solution that may help treat small uncomplicated infantile hemangiomas. This study would examine whether topical timolol could be a potential therapy.

At the first visit, subjects will fill out a questionnaire that asks about the child's history and the hemangioma. Photographs and measurements will be taken at this and each subsequent visit. At the first visit, subjects will have a physical exam, including vital signs, height and weight. An EKG will also be done. Study drug will be dispensed and instructions given. Half of the subjects will receive a placebo. This is a blinded randomized study. Follow-up visits will be weekly for the first two weeks (three visits total including the first visit), then monthly until the study is over. Photographs and measurements will again be taken at each visit. Subjects will be asked to evaluate the size and the color of the hemangioma against the first photographs and fill out forms regarding any changes in behavior and asked about any side effects.

Topical Timolol 0.5% Solution for Proliferating Infantile Hemangiomas

Topical Timolol 0.5% Solution for Proliferating Infantile Hemangiomas: A Prospective Double Blinded Placebo Controlled Study

This will be generated by asking each of the assessors to score the improvement using a visual analog scale (VAS) assessing the decrease in size of hemangioma by comparing photographs at different times of treatment. The assessors will score this improvement into one of the following categories: 0-24%, 25-49%, 50-74%, \>75%.

1. The proportion of subjects in the treatment group as compared to the placebo control group with at least 50% improvement in the extent of the hemangioma.
2. The difference between the extent/size of the hemangioma as an outcome measure versus color changes.
3. Frequency of adverse events (e.g. hypotension, behavioral changes, etc.), collected by the investigator and reported by the parents.

Oregon Health and Science University

Professor

Half of the enrolled subjects (intervention group) will receive topical 0.5% Timolol.

topical 0.5% Timolol: topical 0.5% Timolol aqueous solution, 2-3 drops to cover the hemangioma, twice daily

Topical 0.5% Timolol

Aqueous placebo, 2-3 drops to cover the hemangioma, twice daily

Control (placebo) group: Control (placebo) group

Placebo

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Alfons Krol

Proportion of Subjects in Treatment Group Compared to Placebo Group With at Least 75% Improvement in the Extent of the Hemangioma as Compared to Baseline Photos.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Timolol for the Prevention of Proliferation of Infantile Hemangioma (TiPPIH Trial)	NCT01434849	Infantile Heman... Very Low Birth ...	topical 0.5% Ti... Control (placeb...	- 6 Months	The University of Texas Health Science Center at San Antonio
Topical Timolol 0.5% Solution for Proliferating Infantile Hemangiomas	NCT01147601	Hemangioma Infant	topical 0.5% Ti... Control (placeb...	1 Month - 8 Months	Oregon Health and Science University
Topical Timolol 0.5% Solution for Proliferating Infantile Hemangiomas	NCT01147601	Hemangioma Infant	topical 0.5% Ti... Control (placeb...	1 Month - 8 Months	Oregon Health and Science University
Topical Timolol 0.5% Solution for Proliferating Infantile Hemangiomas	NCT01147601	Hemangioma Infant	topical 0.5% Ti... Control (placeb...	1 Month - 8 Months	Oregon Health and Science University

Spots Global Cancer Trial Database for control (placebo) group