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

NCT01752049 | Completed Phase 1 Results

• 2 other identifiers: BVMC 62072U54NS065705-06
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Hereditary Hemorrhagic Telangiectasia

Keywords

Hereditary Hemorrhagic Telangiectasia; Anti-angiogenic Therapy; vascular malformations; HHT

Outcome Measures

Primary Outcomes (1)

• Change in Lesion Area of Treated Telangiectasia.

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

  84 days

Secondary Outcomes (4)

• Descriptive Changes in Histopathology in Baseline vs Treated Lesions

  84 days

• Serum Angiogenic Markers

  84 days

• Stability of Area of Untreated Telangiectasias Over the 84 Day Period

  84 days

• Blood Flow Velocity and Volume Flow Rates

  84 days

Study Arms (2)

Topical timolol maleate

ACTIVE COMPARATOR

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).

Drug: Topical timolol maleate

Placebo

PLACEBO COMPARATOR

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

Drug: placebo saline drops

Interventions

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

Also known as: Topical timolol maleate 0.5% drops

Topical timolol maleate

placebo saline drops DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

MeSH Terms

Conditions

Telangiectasia, Hereditary Hemorrhagic; Vascular Malformations

Interventions

Timolol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Thiadiazoles; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Morpholines; Oxazines

Results Point of Contact

• Title: Dr. Marie Faughnan
• Organization: St. Michael's Hospital

marie.faughnan@unityhealth.to

416-864-6060

Study Officials

• Marie E Faughnan, MD MSc FRCPC

  Unity Health Toronto

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2012
• First Posted: December 18, 2012
• Study Start: May 1, 2013
• Primary Completion: August 30, 2019
• Study Completion: August 30, 2019
• Last Updated: September 21, 2023
• Results First Posted: September 21, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)