Telangiectasia, Hereditary HemorrhagicPhase 2TEMPONCT02484716
Efficacy of a Timolol Nasal Spray as a Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT) - (TEMPO)
A Phase 2 study testing Timolol nasal spray in people with Telangiectasia, Hereditary Hemorrhagic and Osler Rendu Disease, run by Hospices Civils de Lyon at 1 site in France.
Trial summary
Timolol is a nonselective β-blocker commonly used in the treatment of glaucoma. Recently it has been used topically for the treatment of superficial hemangiomas. Because of its potential mechanism of action, it is possible that timolol could also be useful for the treatment of epistaxis in Hereditary Hemorrhagic… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Telangiectasia, Hereditary Hemorrhagic, Osler Rendu Disease
- What is being tested?
- Timolol nasal spray
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 58 participants
- Where
- 1 siteFrance
- Study dates
- Jun 2015to 29 Jan 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Age > 18 years
- Patients who give voluntary, informed consent and sign a consent form.
- Patients affiliated with the French universal health care system
- Patients treated for HHT, that has been confirmed clinically (presence of at least 3 Curaçao criteria) and/or by molecular biology.
- Patients who present epistaxis averaging over 20 minutes in the three months before inclusion, justified by completed epistaxis tally sheets.
Who cannot join
- Pregnant women or women who could become pregnant during the study, or during lactation
- Patients not affiliated with the French universal health care system
- Patients who are protected adults according to the terms of the law (French public health laws).
- Refusal to give consent.
- Patients whose HHT diagnosis has not be confirmed clinically and/or by molecular biology.
- Participation in another therapeutic trial which could interfere with the present trial (investigator jugement).
Show all 17Show fewer
- Bronchial asthma, presence or history of severe chronic obstructive pulmonary disease
- Cardiac history : cardiac failure or cardiogenic shock. Atrioventricular block (second or third degrees) not controlled with pace-maker or sinus disease (included sinoatrial block) confirmed by ECG less than one year. Ongoing treatment by calcium antagonists (bépridil, diltiazem, verapamil) or antiarrhytmics (propafénone, quinidine, hydroquinidine, disopyramide) or clonidine or lidocaîne. Ongoing beta-blocker treatment.
- Bradycardia (<50 pulse per minute)
- Hypotension (PAS < 90 Hg mm)
- Angina
- Not controlled Pheochromocytoma
- Severe peripheral circulatory disturbances (Raynaud disease)
- Hypersensitivity to the active substance, any of the excipients or other beta-blocking agents
- Ongoing treatment by floctafénine or sultopride or amiodarone
- Patients who do not complete epistaxis grids for three months before treatment
- Patients who present epistaxis averaging below 20 minutes in the three months before inclusion
Trial locations and contacts
1 site in 1 country.
France1 site
Hospices Civils de Lyon - Hôpital Femme Mère Enfant / Service de génétique Clinique
Bron, 69500
About this study
Official title: Efficacy of a Timolol Nasal Spray as a Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT) - Randomized Trial Versus Placebo
Timolol is a nonselective β-blocker commonly used in the treatment of glaucoma. Recently it has been used topically for the treatment of superficial hemangiomas. Because of its potential mechanism of action, it is possible that timolol could also be useful for the treatment of epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT). Moreover a case was reported in 2012 showing an improvement of nosebleeds with the use of topical nasal timolol. The aim of the study is to evaluate timolol nasal spray efficacy in HHT.
The main objective of this trial is to evaluate, 3 months after the end of the treatment, the efficacy on the duration of nosebleeds of a 4 weeks timolol intranasal treatment in HHT patients with nosebleeds (>20 min/month). Secondary objectives are to evaluate the tolerance, the efficacy at 6 months after the end of the treatment, and the efficacy on anemia and on clinical parameters (nosebleeds, quality of life and blood transfusions).
This is a prospective double blind phase II study, randomized versus placebo using an allocation ratio of 1:1. A total of 58 patients will be included. The product (solution with timolol at 0.5% or placebo) is self-administered by the patient with a posology of one spray (50 µL) in each nostril twice a day for 28 consecutive days.
- Being tested
- Timolol nasal spray, Placebo nasal spray
- Keywords
- Hereditary Hemorrhagic Telangiectasia (HHT), Antiangiogenic therapy, Timolol
- Medical subject headings
- Telangiectasia, Hereditary Hemorrhagic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Timolol nasal sprayDrug
Timolol 0.5% is administered by the patient with a posology of one spray (50 µL) in each nostril twice a day for 4 weeks.
Placebo nasal sprayDrug
Placebo (NaCl) is administered by the patient with a posology of one spray (50 µL) in each nostril twice a day for 4 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Timolol | Experimental | Timolol 0.5% eye-drops solution packaged in a nasal spray device. Receives: Drug: Timolol nasal spray |
| Placebo | Placebo comparator | NaCl solution packaged in a nasal spray device. Receives: Drug: Placebo nasal spray |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of timolol nasal spray on duration of nosebleeds for 3 months after the end of the treatment.
comparison of mean monthly epistaxis duration 3 months before the treatment and 3 months after the end of the treatment.
Measured: Day 0 (inclusion) ; up to 4 months
Secondary outcomes (5)
Tolerance of timolol nasal spray in patients with HHT-related epistaxis
Tolerance will be evaluated by observing adverse effects and clinical examinations during the follow up period.
Measured: up to 7 months
Efficacy on clinical criteria : epistaxis frequency .
Comparison of number of epistaxis before and after treatment.
Measured: Day 0 (inclusion) ; up to 4 months
Efficacy on clinical criteria : biological parameters (hemoglobin and ferritin level).
Comparison of hemoglobin and ferritin level before and after treatment.
Measured: Day 0 (inclusion) ; up to 4 months
Efficacy on clinical criteria : quality of life (SF36).
Comparison of SF36 questionnaire before and after treatment.
Measured: Day 0 (inclusion) ; up to 4 months
Efficacy of timolol nasal spray on duration of nosebleeds for 6 months after the end of the treatment.
Comparison of mean monthly epistaxis duration 3 months before the treatment and 6 months after the end of the treatment.
Measured: Day 0 (inclusion) ; up to 7 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2015 (estimated)
- Study startJun 2015
- Primary completionNov 2017
- Study completion29 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Telangiectasia, Hereditary HemorrhagicStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02484716
- Sponsor's protocol ID
- 69HCL15_0063
- Other IDs
- 2015-000385-55, 2015
- Acronym
- TEMPO
- Status last verified
- Aug 2025
- First submitted
- 17 Jun 2015
- Last updated
- 8 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Dupuis-Girod S, Pitiot V, Bergerot C, Fargeton AE, Beaudoin M, Decullier E, Breant V, Colombet B, Philouze P, Faure F, Letievant JC. Efficacy of TIMOLOL nasal spray as a treatment for epistaxis in hereditary hemorrhagic telangiectasia. A double-blind, randomized, placebo-controlled trial. Sci Rep. 2019 Aug 19;9(1):11986. doi: 10.1038/s41598-019-48502-9.
PubMed 31427745
Study at a glance
From the registry record, last updated by the sponsor on 8 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of a Timolol Nasal Spray as a Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT) - Randomized Trial Versus Placebo
- ClinicalTrials.gov ID
- NCT02484716
- Acronym / sponsor ID
- TEMPO / 69HCL15_0063
- Keywords
- Hereditary Hemorrhagic Telangiectasia (HHT), Antiangiogenic therapy, Timolol
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- Jun 2015 (actual)
- Primary completion
- Nov 2017 (actual)
- Study completion
- 29 Jan 2018 (actual)
- First posted
- 30 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Timolol is a nonselective β-blocker commonly used in the treatment of glaucoma. Recently it has been used topically for the treatment of superficial hemangiomas. Because of its potential mechanism of action, it is possible that timolol could also be useful for the treatment of epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT). Moreover a case was reported in 2012 showing an improvement of nosebleeds with the use of topical nasal timolol. The aim of the study is to evaluate timolol nasal spray efficacy in HHT.
The main objective of this trial is to evaluate, 3 months after the end of the treatment, the efficacy on the duration of nosebleeds of a 4 weeks timolol intranasal treatment in HHT patients with nosebleeds (>20 min/month). Secondary objectives are to evaluate the tolerance, the efficacy at 6 months after the end of the treatment, and the efficacy on anemia and on clinical parameters (nosebleeds, quality of life and blood transfusions).
This is a prospective double blind phase II study, randomized versus placebo using an allocation ratio of 1:1. A total of 58 patients will be included. The product (solution with timolol at 0.5% or placebo) is self-administered by the patient with a posology of one spray (50 µL) in each nostril twice a day for 28 consecutive days.
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 |
|---|---|---|
| Timolol | Experimental | Drug: Timolol nasal sprayTimolol 0.5% eye-drops solution packaged in a nasal spray device. |
| Placebo | Placebo comparator | Drug: Placebo nasal sprayNaCl solution packaged in a nasal spray device. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age > 18 years
- Patients who give voluntary, informed consent and sign a consent form.
- Patients affiliated with the French universal health care system
- Patients treated for HHT, that has been confirmed clinically (presence of at least 3 Curaçao criteria) and/or by molecular biology.
- Patients who present epistaxis averaging over 20 minutes in the three months before inclusion, justified by completed epistaxis tally sheets.
Key exclusion criteria (17 listed)
- Pregnant women or women who could become pregnant during the study, or during lactation
- Patients not affiliated with the French universal health care system
- Patients who are protected adults according to the terms of the law (French public health laws).
- Refusal to give consent.
- Patients whose HHT diagnosis has not be confirmed clinically and/or by molecular biology.
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 |
|---|---|---|
| Timolol nasal sprayTimolol 0.5% is administered by the patient with a posology of one spray (50 µL) in each nostril twice a day for 4 weeks. | Drug | Timolol |
| Placebo nasal sprayPlacebo (NaCl) is administered by the patient with a posology of one spray (50 µL) in each nostril twice a day for 4 weeks. | Drug | Placebo |
Primary outcome
Efficacy of timolol nasal spray on duration of nosebleeds for 3 months after the end of the treatment.
Time frame: Day 0 (inclusion) ; up to 4 months
comparison of mean monthly epistaxis duration 3 months before the treatment and 3 months after the end of the treatment.
5 secondary outcomes
Tolerance of timolol nasal spray in patients with HHT-related epistaxis
Time frame: up to 7 months
Efficacy on clinical criteria : epistaxis frequency .
Time frame: Day 0 (inclusion) ; up to 4 months
Efficacy on clinical criteria : biological parameters (hemoglobin and ferritin level).
Time frame: Day 0 (inclusion) ; up to 4 months
Efficacy on clinical criteria : quality of life (SF36).
Time frame: Day 0 (inclusion) ; up to 4 months
Efficacy of timolol nasal spray on duration of nosebleeds for 6 months after the end of the treatment.
Time frame: Day 0 (inclusion) ; up to 7 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2025.
- Results publication: PubMed 31427745Dupuis-Girod S, Pitiot V, Bergerot C, Fargeton AE, Beaudoin M, Decullier E, Breant V, Colombet B, Philouze P, Faure F, Letievant JC. Efficacy of TIMOLOL nasal spray as a treatment for epistaxis in hereditary hemorrhagic telangiectasia. A double-blind, randomized, placebo-controlled trial. Sci Rep. 2019 Aug 19;9(1):11986. doi: 10.1038/s41598-019-48502-9.
- Related InfoLink provided by the sponsor.
Related trials for Telangiectasia, Hereditary Hemorrhagic
Not yet recruitingPhase 1
Topical TOR-582 Treatment of Epistaxis in HHT
Hereditary Hemorrhagic Telangiectasia (HHT), Epistaxis
RecruitingPhase 1/2
Harmony-HHT: ATV-1601 in Participants With Hereditary Hemorrhagic Telangiectasia (HHT)
Hereditary Hemorrhagic Telangiectasia (HHT), Osler Weber Rendu Disease
RecruitingObservational study
Quality of Life in Pediatric Participants With HHT
Hereditary Haemorrhagic Telangiectasia (HHT)
Not yet recruitingObservational study
Prevalence of Obstructive Sleep Apnea in HHT and HHT-specific Challenges in OSA-therapy - a Retrospective Cohort Study
Hereditary Hemorrhagic Telangiectasia (HHT), Obstructive Sleep Apnea (OSA)
Active, not recruitingPhase 1/2
A Study to Evaluate ALN-6400 in Healthy Volunteers and Patients With Hereditary Hemorrhagic Telangiectasia (HHT)
Hereditary Hemorrhagic Telangiectasia
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Timolol nasal spray in people with Telangiectasia, Hereditary Hemorrhagic and Osler Rendu Disease, run by Hospices Civils de Lyon at 1 site in France.
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 5 inclusion and 17 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 8 Aug 2025. 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 France. 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 phase mean?
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Efficacy of timolol nasal spray on duration of nosebleeds for 3 months after the end of the treatment. (time frame: Day 0 (inclusion) ; up to 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02484716, which also lists 1 linked publication.
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 8 Aug 2025.