- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01434849
Timolol for the Prevention of Proliferation of Infantile Hemangioma (TiPPIH Trial) (TiPPIH)
Phase 1 Study of Topical Beta Blocker to Prevent the Proliferative Stage of Infantile Hemangioma
Study Overview
Status
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Texas
-
San Antonio, Texas, United States, 78229-3900
- University of Texas Health Science Center at San Antonio
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Single Group Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Timolol
Application of 1-2 drops of Timolol maleate 0.5% ophthalmic aqueous solution to hemangioma twice daily.
|
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.
|
Aqueous placebo, 1-2 drops to cover the hemangioma, twice daily
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
6 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Compare treatment group to placebo group assessments
Time Frame: 6 months
|
Difference in color of the hemangioma of the treatment group versus control group
|
6 months
|
Compare treatment group to placebo group assessments
Time Frame: 6 months
|
More significant Retinopathy of Prematurity findings between treatment group versus control group
|
6 months
|
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.
|
6 months
|
Collaborators and Investigators
Sponsor
Investigators
- 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
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Congenital Abnormalities
- Body Weight
- Skin Abnormalities
- Neoplasms, Vascular Tissue
- Birth Weight
- Hemangioma, Capillary
- Port-Wine Stain
- Hemangioma
- Physiological Effects of Drugs
- Adrenergic beta-Antagonists
- Adrenergic Antagonists
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Anti-Arrhythmia Agents
- Antihypertensive Agents
- Timolol
Other Study ID Numbers
- HSC20110333H
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Infantile Hemangioma
-
King Edward Medical UniversityCompletedComparison of Efficacy of Sclerotherapy in Infantile HemangiomaPakistan
-
Qilu Hospital of Shandong UniversityCompletedInfantile Haemangiomas
-
Children's Hospital Medical Center, CincinnatiSociety for Pediatric DermatologyCompleted
-
Zhujiang HospitalUnknownInfantile Hemangioma | Capillary Hemangioma | Capillary Hemangiomas | Hemangioma, Capillary Infantile | Strawberry HemangiomaChina
-
Children's Hospital of PhiladelphiaSociety for Pediatric DermatologyWithdrawn
-
Ain Shams UniversityUnknown
-
Joyce TengStanford UniversityNot yet recruiting
-
The Hospital for Sick ChildrenCompleted
-
XiaoXi LinUnknownInfantile HemangiomaChina
-
Columbia UniversityCompleted
Clinical Trials on topical 0.5% Timolol maleate
-
Unity Health TorontoThe Hospital for Sick Children; Sunnybrook Health Sciences Centre; National Institute... and other collaboratorsCompletedHereditary Hemorrhagic TelangiectasiaCanada
-
Pharmaceutical Research NetworkCompleted
-
AllerganCompletedOcular Hypertension | Open-Angle GlaucomaCanada
-
Bp Consulting, IncAllerganCompletedOcular Hypertension | Open-Angle GlaucomaCanada
-
XiaoXi LinUnknownInfantile HemangiomaChina
-
Kanecia Obie ZimmermanNational Institutes of Health (NIH); The Emmes Company, LLCCompletedInfantile HemangiomaUnited States
-
Glaukos CorporationRecruitingOcular Hypertension | Open Angle GlaucomaUnited States
-
Alcon ResearchCompletedOcular Hypertension | Open-angle Glaucoma
-
Pharmaceutical Research NetworkCompleted
-
Alcon ResearchCompletedOcular Hypertension | Open-angle GlaucomaUnited States