Infantile HemangiomaPhase 1TiPPIHNCT01434849
Timolol for the Prevention of Proliferation of Infantile Hemangioma (TiPPIH Trial)
A Phase 1 study testing topical 0.5% Timolol maleate in people with Infantile Hemangioma and Very Low Birth Weight Infants, run by Alice K. Gong at 1 site in United States.
Trial summary
The purpose of this trial is to see if a topical beta blocker is effective in preventing the proliferation of infantile hemangioma. Read more about this study
- Who is it for?
- Ages Up to 6 months
- Conditions the study is for
- Infantile Hemangioma, Very Low Birth Weight Infants
- What is being tested?
- topical 0.5% Timolol maleate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2012to Apr 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 6 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229-3900
About this study
Official title: Phase 1 Study of Topical Beta Blocker to Prevent the Proliferative Stage of Infantile Hemangioma
The purpose of this trial is to see if a topical beta blocker is effective in preventing the proliferation of infantile hemangioma.
Read the 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.
- Being tested
- topical 0.5% Timolol maleate, Control (placebo) group
- Keywords
- infantile hemangioma, very low birth weight infants, premature infants
- Medical subject headings
- Hemangioma, Capillary, Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
topical 0.5% Timolol maleateDrug
topical 0.5% Timolol aqueous solution, 1-2 drops to cover the hemangioma, twice daily
Control (placebo) groupDrug
Aqueous placebo, 1-2 drops to cover the hemangioma, twice daily
| Study group | Role | What they receive |
|---|---|---|
| Timolol | Experimental | Application of 1-2 drops of Timolol maleate 0.5% ophthalmic aqueous solution to hemangioma twice daily. Receives: Drug: topical 0.5% Timolol maleate |
| Placebo | Placebo comparator | Application of 1-2 drops of placebo gel twice daily to hemangioma. Receives: Drug: Control (placebo) group |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
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.
Measured: 6 months
Secondary outcomes (3)
Compare treatment group to placebo group assessments
Difference in color of the hemangioma of the treatment group versus control group
Measured: 6 months
Compare treatment group to placebo group assessments
More significant Retinopathy of Prematurity findings between treatment group versus control group
Measured: 6 months
Compare treatment group to placebo group assessments
Frequency of adverse events (e.g. hypotension, behavioral changes, etc.) collected by investigator and reported by NICU staff and parents.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2011 (estimated)
- Study startJul 2012
- Primary completionApr 2016
- Study completionApr 2016
Why it stopped: Difficulty with enrolled patients to complete trial.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Infantile HemangiomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alice K. Gong
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Alice K. Gong, The University of Texas Health Science Center at San Antonio
- Investigators
- Alice K Gong, M.D., Principal investigator, The University of Texas Health Science Center at San AntonioAlice K Gong, MD, Study director, University of Texas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01434849
- Sponsor's protocol ID
- HSC20110333H
- Acronym
- TiPPIH
- Status last verified
- Nov 2016
- First submitted
- 31 Aug 2011
- Last updated
- 15 Nov 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No: Many participants did not complete trial so there is not enough data to share.
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of Topical Beta Blocker to Prevent the Proliferative Stage of Infantile Hemangioma
- ClinicalTrials.gov ID
- NCT01434849
- Acronym / sponsor ID
- TiPPIH / HSC20110333H
- Keywords
- infantile hemangioma, very low birth weight infants, premature infants
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficulty with enrolled patients to complete trial.
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Alice K. GongUniversity, hospital or other
- Study start
- Jul 2012
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 15 Sep 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Timolol | Experimental | Drug: topical 0.5% Timolol maleateApplication of 1-2 drops of Timolol maleate 0.5% ophthalmic aqueous solution to hemangioma twice daily. |
| Placebo | Placebo comparator | Drug: Control (placebo) groupApplication of 1-2 drops of placebo gel twice daily to hemangioma. |
Who may qualify
- Ages
- Up to 6 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| topical 0.5% Timolol maleatetopical 0.5% Timolol aqueous solution, 1-2 drops to cover the hemangioma, twice daily | Drug | Timolol |
| Control (placebo) groupAqueous placebo, 1-2 drops to cover the hemangioma, twice daily | Drug | Placebo |
Primary outcome
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.
3 secondary outcomes
Compare treatment group to placebo group assessments
Time frame: 6 months
Compare treatment group to placebo group assessments
Time frame: 6 months
Compare treatment group to placebo group assessments
Time frame: 6 months
Results and safety
The study was stopped early (reason given: Difficulty with enrolled patients to complete trial.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2016.
- Individual participant dataSharing planned: No. Many participants did not complete trial so there is not enough data to share.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alice K Gong, M.D. principal investigator
The University of Texas Health Science Center at San Antonio
Alice K Gong, MD study director
University of Texas
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing topical 0.5% Timolol maleate in people with Infantile Hemangioma and Very Low Birth Weight Infants, run by Alice K. Gong at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Difficulty with enrolled patients to complete trial.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2016.