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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2012 by The University of Texas Health Science Center at San Antonio
Sponsor:
Information provided by (Responsible Party):
Alice K. Gong, The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier:
NCT01434849
First received: August 31, 2011
Last updated: January 30, 2013
Last verified: June 2012
  Purpose

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


Condition Intervention Phase
Infantile Hemangioma
Very Low Birth Weight Infants
Prematurity
Drug: topical 0.5% Timolol
Drug: Control (placebo) group
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Phase 1 Study of Topical Beta Blocker to Prevent the Proliferative Stage of Infantile Hemangioma

Resource links provided by NLM:


Further study details as provided by The University of Texas Health Science Center at San Antonio:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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:
  • Compare treatment group to placebo group assessments [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Difference in color of the hemangioma of the treatment group versus control group

  • Compare treatment group to placebo group assessments [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    More significant Retinopathy of Prematurity findings between treatment group versus control group

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


Estimated Enrollment: 42
Study Start Date: July 2012
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Timolol
Application of 1 to drops to hemangioma twice daily
Drug: topical 0.5% Timolol
topical 0.5% Timolol aqueous solution, 1-2 drops to cover the hemangioma, twice daily
Placebo Comparator: Placebo
Application of 1 to 2 drops twice daily to hemangioma.
Drug: Control (placebo) group
Aqueous placebo, 1-2 drops to cover the hemangioma, twice daily

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.

  Eligibility

Ages Eligible for Study:   up to 6 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01434849

Contacts
Contact: Alice K Gong, MD 2105675227 gong@uthscsa.edu
Contact: John C Browning, MD 2105625344 browningj3@uthscsa.edu

Locations
United States, Texas
University of Texas Health Science Center at San Antonio Recruiting
San Antonio, Texas, United States, 78229-3900
Principal Investigator: Alice K Gong, MD         
Sponsors and Collaborators
Alice K. Gong
Investigators
Study Director: Alice K Gong, M.D. The University of Texas Health Science Center at San Antonio
Principal Investigator: Tina Findley, M.D. The University of Texas Health Science Center at San Antonio
  More Information

No publications provided

Responsible Party: Alice K. Gong, Professor of Pediatrics, The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier: NCT01434849     History of Changes
Other Study ID Numbers: HSC20110333H
Study First Received: August 31, 2011
Last Updated: January 30, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by The University of Texas Health Science Center at San Antonio:
infantile hemangioma
very low birth weight infants
premature infants

Additional relevant MeSH terms:
Birth Weight
Hemangioma
Hemangioma, Capillary
Body Weight
Signs and Symptoms
Neoplasms, Vascular Tissue
Neoplasms by Histologic Type
Neoplasms
Timolol
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Antihypertensive Agents

ClinicalTrials.gov processed this record on July 22, 2014