Efficacy of a Timolol Nasal Spray as a Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT) - (TEMPO)

NCT02484716 | Completed Phase 2 DMC

• 2 other identifiers: 69HCL15_00632015-000385-55
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Telangiectasia, Hereditary Hemorrhagic; Osler Rendu Disease

Keywords

Hereditary Hemorrhagic Telangiectasia (HHT); Antiangiogenic therapy; Timolol

Outcome Measures

Primary Outcomes (1)

• 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.

  Day 0 (inclusion) ; up to 4 months

Secondary Outcomes (5)

• Tolerance of timolol nasal spray in patients with HHT-related epistaxis

  up to 7 months

• Efficacy on clinical criteria : epistaxis frequency .

  Day 0 (inclusion) ; up to 4 months

• Efficacy on clinical criteria : biological parameters (hemoglobin and ferritin level).

  Day 0 (inclusion) ; up to 4 months

• Efficacy on clinical criteria : quality of life (SF36).

  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.

  Day 0 (inclusion) ; up to 7 months

Study Arms (2)

Timolol

EXPERIMENTAL

Timolol 0.5% eye-drops solution packaged in a nasal spray device.

Drug: Timolol nasal spray

Placebo

PLACEBO COMPARATOR

NaCl solution packaged in a nasal spray device.

Drug: Placebo nasal spray

Interventions

Timolol nasal spray DRUG

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.

Timolol

Placebo nasal spray DRUG

Placebo (NaCl) is administered by the patient with a posology of one spray (50 µL) in each nostril twice a day for 4 weeks.

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Hospices Civils de Lyon - Hôpital Femme Mère Enfant / Service de génétique Clinique

Bron, 69500, France

Location

Related Publications (1)

• 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.

  PMID: 31427745 RESULT

Related Links

• Related Info

MeSH Terms

Conditions

Telangiectasia, Hereditary Hemorrhagic

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: June 17, 2015
• First Posted: June 30, 2015
• Study Start: June 1, 2015
• Primary Completion: November 1, 2017
• Study Completion: January 29, 2018
• Last Updated: August 8, 2025

Record last verified: 2025-08

Locations

FR (1)