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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by St. Michael's Hospital, Toronto
Sponsor:
Collaborators:
University of California, San Francisco
The Hospital for Sick Children
University of Toronto
Sunnybrook Health Sciences Centre
Ryerson University
Information provided by (Responsible Party):
St. Michael's Hospital, Toronto
ClinicalTrials.gov Identifier:
NCT01752049
First received: December 14, 2012
Last updated: February 12, 2014
Last verified: February 2014

December 14, 2012
February 12, 2014
May 2013
June 2014   (final data collection date for primary outcome measure)
Mean reduction in lesion area (compared with baseline measurement) of treated telangiectasia. [ Time Frame: 84 days ] [ Designated as safety issue: No ]
Mean reduction in lesion area (compared with baseline measurement) of treated telangiectasia.
Same as current
Complete list of historical versions of study NCT01752049 on ClinicalTrials.gov Archive Site
  • 1. From Tissue: Descriptive changes in histopathology in baseline vs treated lesions, vessel density and distribution of capillaries, arterioles and venules. [ Time Frame: 84 days ] [ Designated as safety issue: No ]
    1. From Tissue: Descriptive changes in histopathology in baseline vs treated lesions, vessel density and distribution of capillaries, arterioles and venules.
  • 2. From speckle variance OCT: Changes in lesion area, blood flow velocity and volume flow rates (treated vs baseline/ placebo). [ Time Frame: 84 days ] [ Designated as safety issue: No ]
    2. From speckle variance OCT: Changes in lesion area, blood flow velocity and volume flow rates (treated vs baseline/ placebo).
  • 3. Serum angiogenic markers (Aushon Blood-based Biomarkers in Clinical Research kit, analyzing 5- angiogenic biomarkers): Endoglin, BMP-9, VEGF+, TGF-beta1, TSP-1 [ Time Frame: at baseline and 84 days. ] [ Designated as safety issue: No ]
    3. Serum angiogenic markers (Aushon Blood-based Biomarkers in Clinical Research kit, analyzing 5- angiogenic biomarkers): Endoglin, BMP-9, VEGF+, TGF-beta1, TSP-1
  • 4. Stability of area of untreated telangiectasias over the 84 day period (placebo group) [ Time Frame: 84 days ] [ Designated as safety issue: No ]
    4. Stability of area of untreated telangiectasias over the 84 day period (placebo group)
Same as current
Not Provided
Not Provided
 
Topical Anti-angiogenic Therapy for Telangiectasia in HHT: Proof of Concept
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.

This is a small study of 10 patients from St. Michael's Hospital who have HHT and at least 5 typical telangiectaias.

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. 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 eyedrop, that has been shown to reduce pressure in the eye and is commonly used for glaucoma.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Hereditary Hemorrhagic Telangiectasia (HHT).
  • Drug: Topical timolol maleate
    • 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 4 cutaneous telangiectasias per patient (timolol drops for 3 telangiectasia per patient and placebo drops to 1 telangiectasia per patient).
    Other Name: Topical timolol maleate 0.5% drops
  • Drug: placebo saline drops
    Applied twice daily for 12 weeks (84 days) or until disappearance of lesions to one cutaneous telangiectasias per patient.
    Other Name: placebo saline drops
  • Active Comparator: Topical timolol maleate

    Drug: • Topical timolol maleate 0.5% drops

    • 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 telangiectasia per patient).
    Intervention: Drug: Topical timolol maleate
  • Placebo Comparator: Placebo

    placebo saline drops

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

    Intervention: Drug: placebo saline drops
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
10
June 2014
June 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Definite clinical or genetic diagnosis of HHT
  2. Known ENG or ALK1 mutation (personal or familial)
  3. Age>=18 years
  4. At least 5 typical (round/ovoid, not spider or linear) cutaneous telangiectasia (size range 3-5mm) on dorsum of hands (not including lesions on over inter-phalangeal joints)

Exclusion Criteria:

  1. 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)
  2. Current treatment with systemic beta-blocker
  3. Current participation in other therapeutic trial for HHT
  4. Current pregnancy or breastfeeding.
Both
18 Years and older
No
Contact: Myra E Slutsky, hon BA 416 864 6060 ext 2887 slutskym@smh.ca
Canada
 
NCT01752049
BVMC 6207
No
St. Michael's Hospital, Toronto
St. Michael's Hospital, Toronto
  • University of California, San Francisco
  • The Hospital for Sick Children
  • University of Toronto
  • Sunnybrook Health Sciences Centre
  • Ryerson University
  • National Institute of Neurological Disorders and Stroke (NINDS)
Principal Investigator: Marie E Faughnan, MD MSc FRCPC St. Michael's Hospital, Toronto
St. Michael's Hospital, Toronto
February 2014

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