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

March 19, 2019 updated by: Dr. Alex V. Levin, MD, MHSc, Wills Eye

Primary Objective:

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

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

3

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Wills Eye Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 10 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Timolol
Participants in this group will receive topical timolol
Drug: Timolol
0.5% timolol maleate ophthalmic gel-forming solution applied once
Other Names:
  • Timoptic-XE
Placebo Comparator: Placebo
Participants in this group will receive Preservative free artificial tear gel.
Drug: Preservative free artificial tear gel.
Preservative free artificial tear gel applied topically twice a day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Wills Eye

Collaborators

University of Medicine and Dentistry of New Jersey

Investigators

  • Principal Investigator: Alex V Levin, MD, MHSc, Wills Eye Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2012

Primary Completion (Actual)

January 1, 2019

Study Completion (Actual)

February 1, 2019

Study Registration Dates

First Submitted

February 11, 2012

First Submitted That Met QC Criteria

February 14, 2012

First Posted (Estimate)

February 15, 2012

Study Record Updates

Last Update Posted (Actual)

March 21, 2019

Last Update Submitted That Met QC Criteria

March 19, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AVL-SWS-TT4PWM

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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.

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