Timolol Gel for Epistaxis in Hereditary Hemorrhagic Telangiectasia

• Status: Completed
• Trial end date: 2020-05-20
• Target enrollment: 0
• Participant gender: All

Summary

This study is a double-blinded, randomized controlled trial to evaluate the efficacy of an intranasal topical timolol gel in the care for epistaxis in adults with hereditary hemorrhagic telangiectasia.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Washington University School of Medicine
• Collaborator: Institute of Clinical and Translational Sciences (ICTS)
• Treatments: Timolol

Criteria

Inclusion Criteria:

1. Adults ages 20 and older

2. Confirmed clinical (meeting at least 3 of the 4 Curaçao Criteria) or genetic diagnosis of HHT

3. Epistaxis Severity Score (ESS) ≥ 4 and 2 or more nosebleeds per week with a cumulative nosebleed duration of at least 5 minutes per week

4. Stable nasal hygiene and medical regimen for preceding 1 month

5. Stable epistaxis pattern over the preceding 3 months

Exclusion Criteria:

1. Contraindications for systemic β adrenergic blocker administration

1. Hypersensitivity to β adrenergic blockers

2. Asthma or bronchospasm

3. Congestive heart failure with LVEF <40%

4. Hereditary pulmonary arterial hypertension

5. Baseline bradycardia (HR <55 beats per minute)

6. Sick Sinus Syndrome

7. 2nd or 3rd degree heart block, left or right bundle branch block, or bifasicular block

8. Uncontrolled diabetes mellitus (most recent HbA1c >9%) or diabetic ketoacidosis within last 6 months

9. Hypotension (systolic blood pressure < 90)

2. Known hypersensitivity to timolol

3. Severe peripheral circulatory disturbances (Raynaud phenomenon)

4. Known intermediate or poor metabolizer variant of the liver enzyme CYP2D6

5. Current use of any of the following known strong CYP2D6 inhibitors: fluoxetine (Prozac), paroxetine (Paxil), bupropion (Welbutrin), quinidine, quinine, ritonavir (Norvir), and terbinafine (Lamisil)

6. Current use of the following other drugs known to pharmacodynamically interact with timolol: diltiazem, verapamil, digoxin, digitalis, propafenone, disopyramide, clonidine, flecainide, or lidocaine

7. Patients currently treated or who plan to initiate treatment with β-blockers

8. Use of any anti-angiogenic medication in the last month prior to recruitment, including bevacizumab, pazopanib, thalidomide, or lenalidomide

9. Illicit drug use, except marijuana

10. Known pheochromocytoma

11. Use of anticoagulants, antiplatelet, or fibrinolytic therapies within the last month prior to recruitment, except for low-dose (81 mg or less) of aspirin

12. Pregnancy or planned pregnancy in the next 6 months or currently breastfeeding

13. Inability to read or understand English

14. Inability to complete 8 weeks of therapy for any reason