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NCT Number: NCT01752049

Topical Anti-angiogenic Therapy for Telangiectasia in HHT: Proof of Concept

Hereditary hemorrhagic telangiectasia (HHT) is a hereditary vascular condition characterized by the development of abnormal connections between arteries and veins throughout the body, called vascular malformations. These abnormal blood vessels are referred to as arteriovenous malformations (AVM) if they are large and telangiectasias if they are small. Telangiectasias develop due to irregular growth of blood vessels.

Anti-angiogenic therapy, such as the drug Apo-Timop, curbs the growth of new blood vessels. Apo-Timop is included in a class of medications called beta-blockers. Anti-angiogenic therapies exert their beneficial effects in a number of ways: by disabling the agents that activate and promote cell growth, or by directly blocking the growing blood vessel cells.

The investigators think that anti-angiogenic therapy may lead to the shrinking of telangiectasia in people with HHT. The investigators hope that this study will provide us with proof of this concept and might lead to the development and study of anti-angiogenic therapies to help improve the lives of individuals with vascular malformations.

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Key information

Conditions

Hereditary Hemorrhagic Telangiectasia Cardiovascular Abnormalities Cardiovascular Diseases Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Telangiectasia, Hereditary Hemorrhagic Telangiectasis Vascular Diseases Vascular Malformations

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

About this study

This is a small study of 5 patients from St. Michael's Hospital who have HHT and at least 5 typical telangiectasias.

Patients who anticipate a major surgery during this study or are pregnant, breast feeding or on other beta blocker medication may not enroll in this study.

This study lasts 12 weeks (84 days). During this time, subjects will apply a drop of either Apo-timop 0.5% or a placebo solution to 4 telangiectasias twice daily.

The active study medication is called Apo-Timop and is a clear liquid solution stored in a bottle. An eye dropper is used for application.

  • Apo-timop will be applied to 3 telangiectasias and
  • a placebo will be applied to one telangiectasia A placebo is an inactive substance, with no active medication in it, and it looks the same as the real medication. There is no potential harm of receiving the placebo. It is necessary to use a placebo to make sure that the effect of Apo-timop can be determined without any bias.

Subjects will receive four numbered bottles for every 28 day period as well as a photo which indicates which bottle is to be applied to which telangiectasia.

Neither the subject nor the research staff will know which telangiectasia will receive the placebo.

Apo-timop, is not part of the standard therapeutic regimen for HHT. It is a Health Canada approved medication which is applied as an eye drop, that has been shown to reduce pressure in the eye and is commonly used for glaucoma.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Definite clinical or genetic diagnosis of HHT
  • Known ENG or ALK1 mutation (personal or familial)
  • Age>=18 years
  • At least 5 typical (round/ovoid, not spider or linear) cutaneous telangiectasia (size range 2-5mm) on hands (not including lesions on over inter-phalangeal joints) or face

Exclusion criteria

  • Contraindication to systemic beta-blocker (severe asthma, severe COPD, sinus bradycardia, 2nd or 3rd degree AV block, overt heart failure, hypotension, allergy/intolerance/ hypersensitivity to timolol)
  • Current treatment with systemic beta-blocker
  • Current participation in other therapeutic trial for HHT
  • Current pregnancy or breastfeeding.

Treatment and study plan

Topical timolol maleate

Drug
  • Topical timolol maleate 0.5% drops
  • Applied twice daily for 12 weeks (84 days) or until disappearance of lesions
  • Study drops will be applied to 3 cutaneous telangiectasias per patient

Other names: Topical timolol maleate 0.5% drops

placebo saline drops

Drug

Applied twice daily for 12 weeks (84 days) or until disappearance of lesions to 1 cutaneous telangiectasias per patient.

Primary outcomes

  1. Change in Lesion Area of Treated Telangiectasia.

    Time frame: 84 days

    Change in lesion area (compared with baseline measurement) of treated telangiectasia.

Secondary outcomes

  1. Descriptive Changes in Histopathology in Baseline vs Treated Lesions

    Time frame: 84 days

  2. Serum Angiogenic Markers

    Time frame: 84 days

  3. Stability of Area of Untreated Telangiectasias Over the 84 Day Period

    Time frame: 84 days

  4. Blood Flow Velocity and Volume Flow Rates

    Time frame: 84 days

Sponsors and collaborators

Lead sponsor

Unity Health Toronto

Other

Collaborators

  • National Institute of Neurological Disorders and Stroke (NINDS)
  • Sunnybrook Health Sciences Centre
  • The Hospital for Sick Children
  • Toronto Metropolitan University
  • University of California, San Francisco
  • University of Toronto

Registry information

Important dates

Study start
2013
Primary completion
2019
Study completion
2019
First posted
Dec 18, 2012
Registry last updated
Sep 21, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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