Hereditary Hemorrhagic TelangiectasiaPhase 1/2NCT01752049
Topical Anti-angiogenic Therapy for Telangiectasia in HHT: Proof of Concept
A Phase 1/2 study testing Topical timolol maleate in people with Hereditary Hemorrhagic Telangiectasia, run by Unity Health Toronto at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hereditary Hemorrhagic Telangiectasia
- What is being tested?
- Topical timolol maleate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5 participants
- Where
- 1 siteCanada
- Study dates
- May 2013to 30 Aug 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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
- Being tested
- Topical timolol maleate, placebo saline drops
- Keywords
- Hereditary Hemorrhagic Telangiectasia, Anti-angiogenic Therapy, vascular malformations, HHT
- Medical subject headings
- Telangiectasia, Hereditary Hemorrhagic, Vascular Malformations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Topical timolol maleateDrug
Also called 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
placebo saline dropsDrug
Applied twice daily for 12 weeks (84 days) or until disappearance of lesions to 1 cutaneous telangiectasias per patient.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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. Receives: Drug: placebo saline drops |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Lesion Area of Treated Telangiectasia.
Change in lesion area (compared with baseline measurement) of treated telangiectasia.
Measured: 84 days
Secondary outcomes (4)
Descriptive Changes in Histopathology in Baseline vs Treated Lesions
Measured: 84 days
Serum Angiogenic Markers
Measured: 84 days
Stability of Area of Untreated Telangiectasias Over the 84 Day Period
Measured: 84 days
Blood Flow Velocity and Volume Flow Rates
Measured: 84 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2012 (estimated)
- Study startMay 2013
- Primary completion30 Aug 2019
- Study completion30 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hereditary Hemorrhagic TelangiectasiaStudies of the same condition, open and under way.
- More trials run by Unity Health TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Unity Health Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- University of California, San Francisco, The Hospital for Sick Children, University of Toronto, Sunnybrook Health Sciences Centre, Toronto Metropolitan University, National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Sponsor
- Investigators
- Marie E Faughnan, MD MSc FRCPC, Principal investigator, Unity Health Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01752049
- Sponsor's protocol ID
- BVMC 6207
- Other IDs
- 2U54NS065705-06
- Status last verified
- Aug 2023
- First submitted
- 14 Dec 2012
- Last updated
- 21 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Topical Anti-angiogenic Therapy for Telangiectasia in HHT: Proof of Concept
- ClinicalTrials.gov ID
- NCT01752049
- Acronym / sponsor ID
- BVMC 6207
- Conditions
- Hereditary Hemorrhagic Telangiectasia
- Keywords
- Hereditary Hemorrhagic Telangiectasia, Anti-angiogenic Therapy, vascular malformations, HHT
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Unity Health TorontoUniversity, hospital or other
- Collaborators
- University of California, San Francisco, The Hospital for Sick Children, University of Toronto, Sunnybrook Health Sciences Centre, Toronto Metropolitan University, National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- May 2013
- Primary completion
- 30 Aug 2019 (actual)
- Study completion
- 30 Aug 2019 (actual)
- First posted
- 18 Dec 2012 (estimated)
- Results
- Posted 21 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Topical timolol maleate | Active comparator | Drug: Topical timolol maleateDrug: • 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). |
| Placebo | Placebo comparator | Drug: placebo saline dropsplacebo saline drops -Applied twice daily for 12 weeks (84 days) or until disappearance of lesions to one cutaneous telangiectasias per patient. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Topical timolol maleateAlso: 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 | Drug | Topical timolol maleate |
| placebo saline dropsApplied twice daily for 12 weeks (84 days) or until disappearance of lesions to 1 cutaneous telangiectasias per patient. | Drug | Placebo |
Primary outcome
Change in Lesion Area of Treated Telangiectasia.
Time frame: 84 days
Change in lesion area (compared with baseline measurement) of treated telangiectasia.
4 secondary outcomes
Descriptive Changes in Histopathology in Baseline vs Treated Lesions
Time frame: 84 days
Serum Angiogenic Markers
Time frame: 84 days
Stability of Area of Untreated Telangiectasias Over the 84 Day Period
Time frame: 84 days
Blood Flow Velocity and Volume Flow Rates
Time frame: 84 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marie E Faughnan, MD MSc FRCPC principal investigator
Unity Health Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Topical timolol maleate in people with Hereditary Hemorrhagic Telangiectasia, run by Unity Health Toronto at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Lesion Area of Treated Telangiectasia. (time frame: 84 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2023.