Treatment of Port-wine Mark in Sturge-Weber Syndrome Using Topical Timolol

NCT ID: NCT01533376

Last Updated: 2019-03-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

3 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-02-29

Study Completion Date

2019-02-28

Brief Summary

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Primary Objective:

• To assess the possible utility of topical timolol in the management of port-wine mark (PWM) in Sturge-Weber syndrome in children.

Detailed Description

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Port-wine mark (PWM) represents a congenital capillary malformation,characterized by dilation and malformation of dermal capillaries that lack endothelial proliferation. It is frequently seen in the facial distribution of the trigeminal nerve. PWM persists throughout life and involves \~0.3% of the population. Although PWMs are found in other circumstances, \~ 3% of patients with facial PWM are also afflicted with Sturge-Weber syndrome. PWMs are cosmetic entities that often have serious social consequences, producing psychological trauma to both children and their parents. PWM does not involute with time, and, if left untreated, can develop deep purple coloration, tissue hypertrophy, and nodularity.

Laser therapy, which selectively destroys specific targets within the skin, is currently the most commonly used approach for treating PWM, although complete blanching of the PWM after laser is rarely achieved for most patients, and only 10-45% of patients with Sturge-Weber have shown satisfactory outcomes. Complications of pulsed dye laser treatment for PWM include pyogenic granuloma, scabbing, cutaneous scarring, and permanent hypo/hyperpigmentation. Laser treatment is relatively contraindicated in children with darker skin coloration due to the resulting hypopigmentation which may be equally unsightly. Laser treatment causes substantial discomfort and pain to patients, and often requires general anesthesia in children. This is particularly true since earlier treatment in infancy is desirable and yields increased successful resolution of the PWM. The hypertrophic PWM in later years is resistant to any treatment. Recently, propranolol was reported to successfully treat capillary hemangioma in infants.13 While the mechanism by which beta blockade improves hemangioma is unclear, ß2-mediated vasoconstrictive effects and the ensuing apoptosis of capillary endothelial cells may contribute to the positive therapeutic results.

Oral application of propranolol can cause severe systemic complications, including bronchospasm, vasospasm, hypoglycemia, hypotension, severe bradycardia, heart block, and congestive heart failure. Topical timolol solution, a β-blocker, has shown a similar ability to reduce capillary hemangioma of eyelids with little or no systemic effects in a small pilot study. Similar to capillary hemangioma, which is a proliferative lesion characterized by increased endothelial cell turnover, PWM is a capillary malformation with abnormal endothelial cells and large surface area of dilated capillaries. Thus, both capillary hemangioma and PWM share the similar characteristic of abnormal capillary endothelial cells.

This pilot study is designed to explore the potential role of topical timolol in the management of PWM. As PWM is so frequently associated with Sturge-Weber syndrome, a disorder in which approximately 50% of patients will develop glaucoma, this study will be conducted in an ophthalmology setting.

This study will consist of two arms. One group will receive timolol and the second group a placebo preservative free artificial tear gel. The groups will be divided with a ratio of 1:1 and the Timolol group will be matched with the placebo group by PWM location, age and race.

Both medications are to be applied and rubbed in by fingertip to the treatment site twice a day for 6 months by subject's parents/guardian. (Treatment site: 1x1 cm at inferior edge of facial PWM)

Follow-up schedule: 1 week after treatment initiation and then every 2 months for a period of six months.

Conditions

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Sturge Weber Syndrome Port-wine Mark

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Caregivers

Study Groups

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Timolol

Participants in this group will receive topical timolol

Group Type EXPERIMENTAL

Timolol

Intervention Type DRUG

0.5% timolol maleate ophthalmic gel-forming solution applied once

Placebo

Participants in this group will receive Preservative free artificial tear gel.

Group Type PLACEBO_COMPARATOR

Preservative free artificial tear gel.

Intervention Type DRUG

Preservative free artificial tear gel applied topically twice a day.

Interventions

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Timolol

0.5% timolol maleate ophthalmic gel-forming solution applied once

Intervention Type DRUG

Preservative free artificial tear gel.

Preservative free artificial tear gel applied topically twice a day.

Intervention Type DRUG

Other Intervention Names

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Timoptic-XE

Eligibility Criteria

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Inclusion Criteria

* Age from 2 years to 10 years
* Port-Wine Mark
* English fluent and literate substitute decision maker
* Substitute decision maker vision sufficient to read informed consent document

Exclusion Criteria

* Active ocular infection (conjunctivitis, keratitis,)
* History of systemic conditions including hypo/hypertension, hypoglycemia, bradycardia, asthma or any contraindication to beta blocker use
* Unable to comply with required follow-up
* Substitute decision maker not English fluent or not literate
* Substitute decision maker unable to read consent document
* Patient already using systemic beta-blocker or beta-agonist (Patients already using topical beta-blocker for glaucoma will not be excluded from study).
Minimum Eligible Age

2 Years

Maximum Eligible Age

10 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Medicine and Dentistry of New Jersey

OTHER

Sponsor Role collaborator

Wills Eye

OTHER

Sponsor Role lead

Responsible Party

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Dr. Alex V. Levin, MD, MHSc

Chief, Pediatric Ophthalmology and Ocular Genetics

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Alex V Levin, MD, MHSc

Role: PRINCIPAL_INVESTIGATOR

Wills Eye Institute

Locations

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Wills Eye Institute

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

References

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Hennedige AA, Quaba AA, Al-Nakib K. Sturge-Weber syndrome and dermatomal facial port-wine stains: incidence, association with glaucoma, and pulsed tunable dye laser treatment effectiveness. Plast Reconstr Surg. 2008 Apr;121(4):1173-1180. doi: 10.1097/01.prs.0000304606.33897.71.

Reference Type BACKGROUND
PMID: 18349634 (View on PubMed)

Jia W, Sun V, Tran N, Choi B, Liu SW, Mihm MC Jr, Phung TL, Nelson JS. Long-term blood vessel removal with combined laser and topical rapamycin antiangiogenic therapy: implications for effective port wine stain treatment. Lasers Surg Med. 2010 Feb;42(2):105-12. doi: 10.1002/lsm.20890.

Reference Type BACKGROUND
PMID: 20166161 (View on PubMed)

Chiummariello S, Mezzana P, Fioramonti P, Onesti MG, Alfano C, Scuderi N. The use of laser and Varioscope in the management of hemangiomas and vascular malformations. Acta Chir Plast. 2006;48(1):20-5.

Reference Type BACKGROUND
PMID: 16722347 (View on PubMed)

Li W, Yamada I, Masumoto K, Ueda Y, Hashimoto K. Photodynamic therapy with intradermal administration of 5-aminolevulinic acid for port-wine stains. J Dermatolog Treat. 2010 Jul;21(4):232-9. doi: 10.3109/09546630903159099.

Reference Type BACKGROUND
PMID: 20509816 (View on PubMed)

Kautz G, Kautz I, Segal J, Zehren S. Treatment of resistant port wine stains (PWS) with pulsed dye laser and non-contact vacuum: a pilot study. Lasers Med Sci. 2010 Jul;25(4):525-9. doi: 10.1007/s10103-009-0727-7. Epub 2009 Dec 15.

Reference Type BACKGROUND
PMID: 20013138 (View on PubMed)

Maruani A. [Sturge-Weber syndrome]. Presse Med. 2010 Apr;39(4):482-6. doi: 10.1016/j.lpm.2009.07.030. Epub 2010 Mar 10. French.

Reference Type BACKGROUND
PMID: 20219318 (View on PubMed)

Onesti MG, Fioramonti P, Carella S, Spinelli G, Scuderi N. Surgical and laser treatment of Sturge-Weber syndrome. Aesthetic Plast Surg. 2009 Jul;33(4):666-8. doi: 10.1007/s00266-009-9327-y. Epub 2009 Mar 19.

Reference Type BACKGROUND
PMID: 19296147 (View on PubMed)

Latkowski IT, Wysocki MS, Siewiera IP. [Own clinical experience in treatment of port-wine stain with KTP 532 nm laser]. Wiad Lek. 2005;58(7-8):391-6. Polish.

Reference Type BACKGROUND
PMID: 16425790 (View on PubMed)

Li G, Lin T, Wu Q, Zhou Z, Gold MH. Clinical analysis of port wine stains treated by intense pulsed light. J Cosmet Laser Ther. 2010 Feb;12(1):2-6. doi: 10.3109/14764170903449778.

Reference Type BACKGROUND
PMID: 20085450 (View on PubMed)

Wareham WJ, Cole RP, Royston SL, Wright PA. Adverse effects reported in pulsed dye laser treatment for port wine stains. Lasers Med Sci. 2009 Mar;24(2):241-6. doi: 10.1007/s10103-008-0560-4. Epub 2008 Apr 17.

Reference Type BACKGROUND
PMID: 18418641 (View on PubMed)

Minkis K, Geronemus RG, Hale EK. Port wine stain progression: a potential consequence of delayed and inadequate treatment? Lasers Surg Med. 2009 Aug;41(6):423-6. doi: 10.1002/lsm.20788.

Reference Type BACKGROUND
PMID: 19588535 (View on PubMed)

Izikson L, Nelson JS, Anderson RR. Treatment of hypertrophic and resistant port wine stains with a 755 nm laser: a case series of 20 patients. Lasers Surg Med. 2009 Aug;41(6):427-32. doi: 10.1002/lsm.20793.

Reference Type BACKGROUND
PMID: 19588532 (View on PubMed)

Leaute-Labreze C, Dumas de la Roque E, Hubiche T, Boralevi F, Thambo JB, Taieb A. Propranolol for severe hemangiomas of infancy. N Engl J Med. 2008 Jun 12;358(24):2649-51. doi: 10.1056/NEJMc0708819. No abstract available.

Reference Type BACKGROUND
PMID: 18550886 (View on PubMed)

Siegfried EC, Keenan WJ, Al-Jureidini S. More on propranolol for hemangiomas of infancy. N Engl J Med. 2008 Dec 25;359(26):2846; author reply 2846-7. doi: 10.1056/NEJMc086443. No abstract available.

Reference Type BACKGROUND
PMID: 19109584 (View on PubMed)

Guo S, Ni N. Topical treatment for capillary hemangioma of the eyelid using beta-blocker solution. Arch Ophthalmol. 2010 Feb;128(2):255-6. doi: 10.1001/archophthalmol.2009.370. No abstract available.

Reference Type BACKGROUND
PMID: 20142555 (View on PubMed)

Other Identifiers

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AVL-SWS-TT4PWM

Identifier Type: -

Identifier Source: org_study_id

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