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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Wills Eye
Sponsor:
Collaborator:
University of Medicine and Dentistry of New Jersey
Information provided by (Responsible Party):
Dr. Alex V. Levin, MD, MHSc, Wills Eye
ClinicalTrials.gov Identifier:
NCT01533376
First received: February 11, 2012
Last updated: June 13, 2013
Last verified: June 2013
  Purpose

Primary Objective:

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


Condition Intervention Phase
Sturge Weber Syndrome
Port Wine Mark
Drug: Timolol
Drug: Preservative free artificial tear gel.
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Official Title: Treatment of Port-wine Mark in Sturge-Weber Syndrome Using Topical Timolol

Resource links provided by NLM:


Further study details as provided by Wills Eye:

Primary Outcome Measures:
  • Appearance of Port-wine Mark at treatment site [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Changes of color and size of PWM at treatment site will determine efficacy of the topical timolol.


Estimated Enrollment: 10
Study Start Date: February 2012
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Timolol
Participants in this group will receive topical timolol
Drug: Timolol
0.5% timolol maleate ophthalmic gel-forming solution applied once
Other Name: 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.

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.

  Eligibility

Ages Eligible for Study:   2 Years to 10 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01533376

Contacts
Contact: Jose A Cordovez, MD 2159283418 jcordovez@willseye.org
Contact: Alex V Levin, MD, MHSc 2159283918 alevin@willseye.org

Locations
United States, Pennsylvania
Wills Eye Institute Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Jose A Cordovez, MD    215-928-3418    jcordovez@willseye.org   
Contact: Alex V Levin, MD, MHSc    2159283918    alevin@willseye.org   
Principal Investigator: Alex V Levin, MD, MHSc         
Sponsors and Collaborators
Wills Eye
University of Medicine and Dentistry of New Jersey
Investigators
Principal Investigator: Alex V Levin, MD, MHSc Wills Eye Institute
  More Information

Publications:

Responsible Party: Dr. Alex V. Levin, MD, MHSc, Chief, Pediatric Ophthalmology and Ocular Genetics, Wills Eye
ClinicalTrials.gov Identifier: NCT01533376     History of Changes
Other Study ID Numbers: AVL-SWS-TT4PWM
Study First Received: February 11, 2012
Last Updated: June 13, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Wills Eye:
Sturge Weber
SWS
Timolol
Port wine mark

Additional relevant MeSH terms:
Klippel-Trenaunay-Weber Syndrome
Sturge-Weber Syndrome
Neurocutaneous Syndromes
Brain Stem Infarctions
Angiomatosis
Vascular Diseases
Cardiovascular Diseases
Hemangioma
Neoplasms, Vascular Tissue
Neoplasms by Histologic Type
Neoplasms
Nervous System Diseases
Brain Infarction
Brain Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Stroke
Ophthalmic Solutions
Timolol
Pharmaceutical Solutions
Therapeutic Uses
Pharmacologic Actions
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Arrhythmia Agents

ClinicalTrials.gov processed this record on August 01, 2014