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| ID | Type | Description | Link |
|---|---|---|---|
| 2U54NS065705-06 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| University of California, San Francisco | OTHER |
| The Hospital for Sick Children | OTHER |
| University of Toronto | OTHER |
| Sunnybrook Health Sciences Centre |
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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 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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Topical timolol maleate | Active Comparator | Drug: • Topical timolol maleate 0.5% drops
|
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Topical timolol maleate | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Lesion Area of Treated Telangiectasia. | Change in lesion area (compared with baseline measurement) of treated telangiectasia. | 84 days |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Marie E Faughnan, MD MSc FRCPC | Unity Health Toronto | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| St. Michael's Hospital | Toronto | Ontario | M5B 1W8 | Canada |
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Each Participant received both treatment and placebo
| ID | Title | Description |
|---|---|---|
| FG000 | Topical Timolol Maleate | Topical timolol maleate 0.5% drops will be applied twice daily for 12 weeks (84 days) or until disappearance of lesions on 3 cutaneous telangiectasias per patient (total of 5 patients) |
| FG001 | Placebo | placebo saline drops will be applied twice daily for 12 weeks (84 days) or until disappearance of lesions to one cutaneous telangiectasias per patient (same 5 patient as Topical treatment group) |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Total 5 participants treated (15 treatment lesions and 5 placebo lesions)
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants | Drug: • Topical timolol maleate 0.5% drops
Topical timolol maleate: • Topical timolol maleate 0.5% drops
|
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Lesion Area of Treated Telangiectasia. | Change in lesion area (compared with baseline measurement) of treated telangiectasia. | 5 participants enrolled, each participant have Hereditary Hemorrhagic Telangiectasia (HHT) and have at least 5 typical telangiectasias on their hands or face. | Posted | Geometric Mean | Standard Deviation | mm^2 | 84 days | Lesion (Telangiectasia) | Lesion (Telangiectasia) |
|
84 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Topical Timolol Maleate | 5 patients received Topical timolol maleate 0.5% drops. Applied twice daily for 12 weeks (84 days) Study drops were applied to 3 cutaneous telangiectasias per patient. Each patient had 2 lesional biopsies (one at baseline, and one at end of treatment) |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Minor infection at biopsy site | Skin and subcutaneous tissue disorders | Non-systematic Assessment | expected adverse event -Biopsy site |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Marie Faughnan | St. Michael's Hospital | 416-864-6060 | 5412 | marie.faughnan@unityhealth.to |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 1, 2014 | Jan 7, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D013683 | Telangiectasia, Hereditary Hemorrhagic |
| D054079 | Vascular Malformations |
| ID | Term |
|---|---|
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D013684 | Telangiectasis |
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| ID | Term |
|---|---|
| D013999 | Timolol |
| ID | Term |
|---|---|
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
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| OTHER |
| Toronto Metropolitan University | OTHER |
| National Institute of Neurological Disorders and Stroke (NINDS) | NIH |
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|
| placebo saline drops | Drug | Applied twice daily for 12 weeks (84 days) or until disappearance of lesions to 1 cutaneous telangiectasias per patient. |
|
| 84 days |
| Blood Flow Velocity and Volume Flow Rates | 84 days |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
The same 5 participants will receive placebo saline drops on one cutaneous telangiectasia. Applied twice daily for 12 weeks (84 days) or until disappearance of lesions to one cutaneous telangiectasias per patient.
|
|
| Secondary | Descriptive Changes in Histopathology in Baseline vs Treated Lesions | No data collected | Posted | 84 days |
|
|
| Secondary | Serum Angiogenic Markers | No data collected | Posted | 84 days |
|
|
| Secondary | Stability of Area of Untreated Telangiectasias Over the 84 Day Period | No data collected | Posted | 84 days |
|
|
| Secondary | Blood Flow Velocity and Volume Flow Rates | No data collected | Posted | 84 days |
|
|
| 0 |
| 5 |
| 0 |
| 5 |
| 1 |
| 5 |
| EG001 | Placebo | The same 5 patients received placebo saline drops for one telangiectasia each. The placebo drops were applied twice daily for 12 weeks (84 days) | 0 | 5 | 0 | 5 | 1 | 5 |
|
| Minor bleeding at biopsy site | Skin and subcutaneous tissue disorders | Non-systematic Assessment | expected adverse event -Biopsy site |
|
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| D006474 |
| Hemorrhagic Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D018376 | Cardiovascular Abnormalities |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D020005 |
| Propanols |
| D000588 | Amines |
| D013830 | Thiadiazoles |
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009025 | Morpholines |
| D010078 | Oxazines |