Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02484716
Recruitment Status : Completed
First Posted : June 30, 2015
Last Update Posted : February 1, 2018
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon

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.


Condition or disease Intervention/treatment Phase
Hemorrhagic Hereditary Telangiectasia (HHT) Drug: Timolol nasal spray Drug: Placebo nasal spray Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 58 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy of a Timolol Nasal Spray as a Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT) - Randomized Trial Versus Placebo
Actual Study Start Date : June 2015
Actual Primary Completion Date : November 2017
Actual Study Completion Date : January 29, 2018


Arm Intervention/treatment
Experimental: Timolol
Timolol 0.5% eye-drops solution packaged in a nasal spray device.
Drug: Timolol nasal spray
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 Comparator: Placebo
NaCl solution packaged in a nasal spray device.
Drug: Placebo nasal spray
Placebo (NaCl) is administered by the patient with a posology of one spray (50 µL) in each nostril twice a day for 4 weeks.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Tolerance of timolol nasal spray in patients with HHT-related epistaxis [ Time Frame: up to 7 months ]
    Tolerance will be evaluated by observing adverse effects and clinical examinations during the follow up period.

  2. Efficacy on clinical criteria : epistaxis frequency . [ Time Frame: Day 0 (inclusion) ; up to 4 months ]
    Comparison of number of epistaxis before and after treatment.

  3. Efficacy on clinical criteria : biological parameters (hemoglobin and ferritin level). [ Time Frame: Day 0 (inclusion) ; up to 4 months ]
    Comparison of hemoglobin and ferritin level before and after treatment.

  4. Efficacy on clinical criteria : quality of life (SF36). [ Time Frame: Day 0 (inclusion) ; up to 4 months ]
    Comparison of SF36 questionnaire before and after treatment.

  5. 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 ]
    Comparison of mean monthly epistaxis duration 3 months before the treatment and 6 months after the end of the treatment.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02484716


Locations
Layout table for location information
France
Hospices Civils de Lyon - Hôpital Femme Mère Enfant / Service de génétique Clinique
Bron, France, 69500
Sponsors and Collaborators
Hospices Civils de Lyon

Additional Information:
Layout table for additonal information
Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT02484716     History of Changes
Other Study ID Numbers: 69HCL15_0063
2015-000385-55 ( EudraCT Number )
First Posted: June 30, 2015    Key Record Dates
Last Update Posted: February 1, 2018
Last Verified: January 2018
Keywords provided by Hospices Civils de Lyon:
Hemorrhagic Hereditary Telangiectasia (HHT)
Antiangiogenic therapy
Timolol
Additional relevant MeSH terms:
Layout table for MeSH terms
Epistaxis
Telangiectasis
Telangiectasia, Hereditary Hemorrhagic
Vascular Diseases
Cardiovascular Diseases
Nose Diseases
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Hemorrhage
Pathologic Processes
Signs and Symptoms, Respiratory
Signs and Symptoms
Hemostatic Disorders
Hemorrhagic Disorders
Hematologic Diseases
Vascular Malformations
Cardiovascular Abnormalities
Congenital Abnormalities
Timolol
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Antihypertensive Agents