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

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01533376
Recruitment Status : Recruiting
First Posted : February 15, 2012
Last Update Posted : April 25, 2018
University of Medicine and Dentistry of New Jersey
Information provided by (Responsible Party):
Dr. Alex V. Levin, MD, MHSc, Wills Eye

February 11, 2012
February 15, 2012
April 25, 2018
February 2012
December 2019   (Final data collection date for primary outcome measure)
Appearance of Port-wine Mark at treatment site [ Time Frame: 12 months ]
Changes of color and size of PWM at treatment site will determine efficacy of the topical timolol.
Same as current
Complete list of historical versions of study NCT01533376 on Archive Site
Not Provided
Not Provided
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Treatment of Port-wine Mark in Sturge-Weber Syndrome Using Topical Timolol
Treatment of Port-wine Mark in Sturge-Weber Syndrome Using Topical Timolol

Primary Objective:

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

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.

Phase 1
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
  • Sturge Weber Syndrome
  • Port-wine Mark
  • Drug: Timolol
    0.5% timolol maleate ophthalmic gel-forming solution applied once
    Other Name: Timoptic-XE
  • Drug: Preservative free artificial tear gel.
    Preservative free artificial tear gel applied topically twice a day.
  • Experimental: Timolol
    Participants in this group will receive topical timolol
    Intervention: Drug: Timolol
  • Placebo Comparator: Placebo
    Participants in this group will receive Preservative free artificial tear gel.
    Intervention: Drug: Preservative free artificial tear gel.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Same as current
December 2019
December 2019   (Final data collection date for primary outcome measure)

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).
Sexes Eligible for Study: All
2 Years to 10 Years   (Child)
Contact: Waleed K Abed Alnabi, MD 2159283418
Contact: Alex V Levin, MD, MHSc 2159283918
United States
Not Provided
Plan to Share IPD: No
Dr. Alex V. Levin, MD, MHSc, Wills Eye
Wills Eye
University of Medicine and Dentistry of New Jersey
Principal Investigator: Alex V Levin, MD, MHSc Wills Eye Institute
Wills Eye
April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP