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

NCT ID: NCT01752049

Last Updated: 2023-09-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-31
• Study Completion Date: 2019-08-30

Brief Summary

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.

Detailed Description

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.

Conditions

Hereditary Hemorrhagic Telangiectasia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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).

Group Type: ACTIVE_COMPARATOR

Topical timolol maleate

Intervention Type: 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

Placebo

placebo saline drops

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

Group Type: PLACEBO_COMPARATOR

placebo saline drops

Intervention Type: DRUG

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

Interventions

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 3 cutaneous telangiectasias per patient

Intervention Type: DRUG

placebo saline drops

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

Intervention Type: DRUG

Other Intervention Names

Topical timolol maleate 0.5% drops

Eligibility Criteria

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 2-5mm) on hands (not including lesions on over inter-phalangeal joints) or face

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, San Francisco

OTHER

Sponsor Role: collaborator

The Hospital for Sick Children

OTHER

Sponsor Role: collaborator

University of Toronto

OTHER

Sponsor Role: collaborator

Sunnybrook Health Sciences Centre

OTHER

Sponsor Role: collaborator

Toronto Metropolitan University

OTHER

Sponsor Role: collaborator

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Unity Health Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marie E Faughnan, MD MSc FRCPC

Role: PRINCIPAL_INVESTIGATOR

Unity Health Toronto

Locations

St. Michael's Hospital

Toronto, Ontario, Canada

Countries

Canada

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2U54NS065705-06

Identifier Type: NIH

Identifier Source: secondary_id

View Link

BVMC 6207

Identifier Type: -

Identifier Source: org_study_id