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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01434849
Recruitment Status : Terminated (Difficulty with enrolled patients to complete trial.)
First Posted : September 15, 2011
Last Update Posted : November 15, 2016
Information provided by (Responsible Party):
Alice K. Gong, The University of Texas Health Science Center at San Antonio

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

Condition or disease Intervention/treatment Phase
Infantile Hemangioma Very Low Birth Weight Infants Drug: topical 0.5% Timolol maleate Drug: Control (placebo) group Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Phase 1 Study of Topical Beta Blocker to Prevent the Proliferative Stage of Infantile Hemangioma
Study Start Date : July 2012
Actual Primary Completion Date : April 2016
Actual Study Completion Date : April 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Birthmarks

Arm Intervention/treatment
Experimental: Timolol
Application of 1-2 drops of Timolol maleate 0.5% ophthalmic aqueous solution to hemangioma twice daily.
Drug: topical 0.5% Timolol maleate
topical 0.5% Timolol aqueous solution, 1-2 drops to cover the hemangioma, twice daily

Placebo Comparator: Placebo
Application of 1-2 drops of placebo gel twice daily to hemangioma.
Drug: Control (placebo) group
Aqueous placebo, 1-2 drops to cover the hemangioma, twice daily

Primary Outcome Measures :
  1. Proportion of subjects in treatment group compared to placebo group with at least 50% improvement in the extent of hemangioma as compared to each other with respect to changes from baseline photographs. [ Time Frame: 6 months ]
    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.

Secondary Outcome Measures :
  1. Compare treatment group to placebo group assessments [ Time Frame: 6 months ]
    Difference in color of the hemangioma of the treatment group versus control group

  2. Compare treatment group to placebo group assessments [ Time Frame: 6 months ]
    More significant Retinopathy of Prematurity findings between treatment group versus control group

  3. Compare treatment group to placebo group assessments [ Time Frame: 6 months ]
    Frequency of adverse events (e.g. hypotension, behavioral changes, etc.) collected by investigator and reported by NICU staff and parents.

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 6 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01434849

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United States, Texas
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229-3900
Sponsors and Collaborators
Alice K. Gong
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Principal Investigator: Alice K Gong, M.D. The University of Texas Health Science Center at San Antonio
Study Director: Alice K Gong, MD University of Texas
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Responsible Party: Alice K. Gong, Professor of Pediatrics, The University of Texas Health Science Center at San Antonio Identifier: NCT01434849    
Other Study ID Numbers: HSC20110333H
First Posted: September 15, 2011    Key Record Dates
Last Update Posted: November 15, 2016
Last Verified: November 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Many participants did not complete trial so there is not enough data to share.
Keywords provided by Alice K. Gong, The University of Texas Health Science Center at San Antonio:
infantile hemangioma
very low birth weight infants
premature infants
Additional relevant MeSH terms:
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Hemangioma, Capillary
Port-Wine Stain
Birth Weight
Body Weight
Neoplasms, Vascular Tissue
Neoplasms by Histologic Type
Skin Abnormalities
Congenital Abnormalities
Skin Diseases
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Antihypertensive Agents